BIOENGINEERING AND WORLD HEALTH
BIOENGINEERING AND WORLD HEALTH BIOE 301
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Outline The burden of heart disease BM E 1 The cardiovascular system How do heart attacks happen How do we treat atherosclerosis Open heart surgery Angioplasty 39 I smns LeCture Flfteen What is heart failure How do we treat heart failure Heart tranwlant Left ventricular assist devices I Arti cial heat Early Warning Signs of Heart Attack Many heat attacks stat slowly sympmms may come and o chest discomfort Most heart attaoks ll39lvolve discomfort in the center of the thest thatlasts for more than a few miru es or goes away and oomes back The discomfort can feel like uncomfortable pressure squeezll39vg fullness or pain 39 eas of the upper body can inoude pain or disoomfortin one or both arms the badlt neck Jaw or stomach often oomes along with chest dsoomfort But it also can occur before dnest discomfort other sy mms May include breaking out in a cold sweat nausea or llghts headedness Heart Attack Video httg wwwheartlcomZattacnguidanth m Healt Attacks Diagnosis of Atherosclerosis Detection of Atherosclerosis Len Coronary Artery Heart Attacks Treatment of Atherosclerosis How Do We Treat Atherosclerosis CABG Cxmrnry aviary hymns om39l up rower Coronary Amery Bypass Graft Len Internal Mammary Artery Anna 7 Narrowian in coronary artery CABG Procedure Patient is prepped general anesthesia Chest access is gained through sternum Graft vessel is retrieved Expose heart through pericardium Divert blood through heart lung machine Stop heart Insert graft Return circulation to heart Close incision htt wwwctsnetor doc 3311 Heart Lung Machine I The heart lung machine Consists of a chamber that receives the blood from the body Blood is pumped by machine through an oxygenator Oxygenator removes C02 and adds oxygen Pump then pumps this newly oxygenated blood back to the body Connected to patient by a series of tubes that the surgical team places Heart Lu a Heart Lung Machine nrmz39r ox mimian oxnu nymss mam mwa nun mm m l r 1VA mm Al u mp wamma mmetawi arr Heart Lung Machine l warn minim retrain r nip Hangmawatmsmaam an ar CABG Effectiveness 2001 516000 CABG procedures performed Procedure takes 46 hours 57 day hospital stay Grafts remain open amp functioning for 1015 yrs Risks Heart attack 5 I Stroke 5 risk greatest in those over 70 years old Death 12010 Sternal wound infection 14 I Postpericardiotomy syndrome 30 H1 afEr surgery Symptoms are fever and chest pain I Some people report memory loss and loss of mental clarity or quotfuzzy thinkingquot following CABG Innovations I Off pump CABG I Closed chest CABG 9 11mm reromrn comEtoriesLstK How Do We Treat Atherosclerosis Angioplasty Balloon Aimrmlornllc Nnrruwadlurnan Coronary pleqm ulmery emery Balloon cameiu Min ooslruwzd an In an Allor lumnn widen balloon camalar with dullalad balloon is VileVn BALLOON AN GIOPLASTY PTCA Effectiveness Cannot always successfully perform procedure Diffuse disease Total occlusion Calci ed disease Restenosis Occurs in 2554 of patients Usually occurs within 6 months How Do We Treat Atherosclerosis Stent Stents How is a Coronary Stent Implanted Amva in WWW m mm mm um um t whim m m mesmnr M Na W m mm s imm mu my WWW xx my wrodmrmvumtmnm Drug Eluting Stents I httpwwwnprorgfeaturesfeaturephp w d1452217 Comparison of RX Methods I Hospital Stay I CABG 47 days I Angioplasty 12 days I Stent 12 days I Restenosis I CABG 56 usually after 5 years I Angioplasty 2545 usually within 6 mont s I Stent 1520 usually within 6 months Comparison of RX Methods Cost CABG 35000 Angioplasty 17000 Stent 19000 I Costeffectiveness I Additive procedures Wilhll l 5 yeas 20740 ofpauenE have second PTCA 25 have CABG I Additive cosls 0 vars per palth cosB of PTCA 3060 those of CABG lyear 5075M I Moving Target Roblem What Would You Do Angioplasty Stent I CABG Prevention or Treatment httpzwwwnytimescom20040321zheal th ZlHEARhtml Cost Effectiveness per yr Post MI 24200 MI treatment started gt2 cessation 920042500 Progression of Heart Disease Hi h Blood Pressure High Cholesterol Levels Heart Failure Atherosclerosis Heart Attack Ischemia Assignments Due Next Time HW 7 Chapter 12 problems 3 7 8 10 BIOE 301 Lecture Seventeen Progression of Heart Disease High Blood Pressure High Cholesterol Levels Heart Failure Atherosclerosis Heart Attack Ischemia Review of Last Time I What is heart failure I Occurs when left or right ventricle loses the ability to keep up with amount of blood flow I How do we treat heart failure I Heart transplant I Rejection inadequate supply of donor hearts I LVAD I Can delay progression of heart failure I Artificial heart Artificial Heart History I First artificial heart implanted in 1969 I No more human trials until the 19805 History of Artificial Heart muwmmnmmtmumm may e 2001 I ht discover nir org feat ures trn 7W 111 am August 2001 I ht discover nr or feat ures tm 7W 111 I November 2001 ht discovern ror feat 332g0 7 AbioCor Arti cial Heart I httpwwwheartpion eerscomnewsimages htm I Cost 70100k in 0mm mmm WWWWhMMDWM w Clinical Trial of AbioCor I Goals of Initial Clinical Trial I Determine whether AbioCorTM can extend life With acceptable quality for patients With less 30 days to live and no other therapeutic alternative I To learn what we need to know to deliver the next generation of AbioCor to treat a broader patient population for longer life and improving quality of 39fe r m Clinical Trial of AbioCor I Patient Inclusion Criteria highlights I Biventricular heart failure I Greater than eighteen yars old I High likelihood of dying within the next thirty days I Unresponsive to maximum existing therapies I Ineligible for cardiac transplantation I Succssful AbioFit M analysis I Patient Exclusion Criteria highlights I Hart failure with signi cant potential for reversibility I Life expectancy gt30 da s I Serious noncardiac disease I Pregnancy I Psychiatric illness including drug or alcohol abuse I Inadequate social support system Clinical Trial of AbioCor I Clinical Trial Endpoints I Allcause mortality through sixty days I Quality of Life measurements I Repeat QOL assessments at 30day intervals until death I Number of patients I Initial authorization for five 5 implants I Expands to fifteen 15 patients in increments of five 5 if 60day experience is satisfactory to FDA Consent Form I httpwwwabiomedcomFabiocorhtml I httpMMM 39 comDubliccas eszABIOMED 1Casepdf Prevention of Heart Disease I 1990s I Small series of trials suggested that high doses of Vitamin E might reduce risk of developing heart disease by 40 I 1996 Randomized clinical trial I 1035 patients taking vitamin E I 967 patients taking placebo I Vitamin E provides a protective effect Prevention of Heart Disease I 2000 pivotal clinical trial I 9541 patients I No benefit to Vitamin E I Followed for 7 years may increase risk of disease I What happened Challenges Clinical Research I Early studies small patients I Generate hypotheses I Larger studies I Rigoroust test hypotheses I Due to biological variability I Larger studies often contradict early studies I Recent study I 13 of highly cited studies later contradicted I More frequent if patients aren t randomized Types of Clinical Studies I Hypothesis Generation I Case study case series examine patient or group of patients with similar illness I Hypothesis Testing I Observational I Identify group of patients with and without disease Collect ata Use to test our hypothesis I Advantage Easy cheap I Disadvantage Bias Can39t control the intenentional to decisively show cause and effect Types of Clinical Studies I Hypothesis Testing I Experimental I Clinical trial Research study to evaluate effect of an intervention on patien I Isolate all but a single variable and measure the effect of the variable I Done prospectively Plan then execute I Single arm study Take patients give intenenu39on compare to baseline Can suffer from placebo ect I Randomized clinical trials Different subjects are randomly assigned to get the treatment or the contra Planning a Randomized Clinical Trial I Two arms I Treatment group I Control group I Outcome I Primary outcome I Secondary outcomes I Sample size I Want to ensure that any differences between treatment and control group are real I Must consider available Example Planning a Clinical Trial I New drug eluting stent I Treatment group I Control group I Primary Outcome I Secondary Outcomes Sample Size Calculation I There will be some statistical uncertainty associated with the measured restenosis rate I Goal I Uncertainty ltlt Difference in primary outcome between control amp treatment group I Choose our sample size so that this is true Types of Errors in Clinical Trial I TypeI Error I We mistakenly conclude that there is a difference be een e 0 groups when in reality there is no difference I Type 11 Error I We mistakenly conclude that there is not a difference be een e two when in reality there is a difference I Choose our sam le size I Acceptable likelihood of Type I or 11 error I Enough ss to carry out the trial Types of Errors in Clinical Trial I Type I Error I We mistakenly conclude that there is a difference between the two rou S I pnvalue e probablllty of maklng a Type l error 5 I Usually setp 1 e I We mlstakenly conclude tnat there is nor a dlfference between e I Beta e probablllty of maklng a Type 11 error I P Wer e pmbablllty or maltlng a Type u errur I Usually set beta 10 e 20 How do we calculate n I Select primary outcome I Estimate expected rate of primary utcome in I Treatment group I Control group I Set acceptable levels of Type I and 11 error I Choose pvalue I Choose beta How do we calculate n I Calculate standardized difference SD Pllesqrtp1 p p mpg2 I P1 39action of patients in treatment group who experience primary outcome I P2 39action of patients in control group who experience primary outcome I Use Altman39s nomogram to determine n Drug Eluting Stent Sample Size I Treatment group I Recelye stent I Stent 10 I Angloplasty 45 I Error ra s I SD 078 quot439quot Data amp Safety Monitoring Boards I DSMB I Special committees to monitor interim results in clinical trials I Federal rules recpire all phase III trials be monitored by DSMBs I Can stop trial early I New treatment offered to both groups I Prevent addluonal harm DSMBS I New treatment for sepsis I New drug I Placebo I n 1500 I Interim analysis after 722 patients I Mortality in placebo group 389 I Mortality in treatment group 291 I Signi cant at the p 0006 level I Should the study be stopped DSMBS I Decision I No I Neither researchers nor subjects were informed I Outcome I Mortality in placebo group 339 I Mortality in treatment group 342 I Difference was neither clinically nor statistically significant I Informed consents should be modified to indicate if a trial is monitored by a DSMB Assignments Due Next Time st I Chapter 13 problems 2 3 and 5 I Egtltam Two I November 18m I Can bring one 85 x 11quotnote sheet BIOE 301 Lecture Eighteen e Semp e size cagcuma ms a Ehepre eii T eheheee heeitmeht were grepp ree Type I ETTOTS Fellse Pesmhve e kehh ephepipe hhe39re hehh gTrpppeg wheh h reehgy he hTerehee e pew e39he e pw39feheh l hy T K hg hyp I TTCOT Type II ETTDTE Felipe Negative e MTeTeKehhr the hhewe het wheh Uh e 2 phehemhh eff meth TI ehpp Choose our semp e size a Hifikehheee effquot Type Ti er ET ewe e Ehepgh he TW he The GE e F Drug E u ng Steam 6 Samp g Size 39 sz mm pm a L929 55 39 a w ammbsw patients required a WWW Ln39ereame 11 mm It a gram c lNh ejWEEiEgI 4 a IEWW39 W c Li S 5 a 3132 E 72 39 T Science of Understanding Disease Emerging Health Technologies Ethics of research Clinical Trials CostEffectiveness o ethical concerns legal issues 0 social issues 0 economic issues Di usmon is hstorical y slow I 14971 a eme met em f39 yew memfnilbere ecwi w ee li mg Ffquot G Hikepe emme Cepme 1 it 16013 a Ewr fi eh N W Celp tem Jemee Lemrgeeter in Cemmfmemj 4 ewe tarewel mg Efrem Emg end t Imd e Li Required sewers t0 Elke 3 Bap of liemm imam de My on 1 ship g The Wiser 3 sh m as me mm 1 Reew teg n 11WZ78 ea ars died in mm gmgp Li 0 dee he rm bre expe imemm group it 1747 1 BIFWEUSW New Phye e em Mme wrepeetecdi SLEWJV with Simmer meewJ Lte 1 18653 a Bf t eh New 391 f em I mew edep tedl imme W Weeme es ter leme 1 Bemy ccikg D me roj Dweeemme mg Hmmve fene m Heede JAMA AMI i 235 V M Ne 15 Chara 12 who adopt Change m mm Figure 2 Adopter Categorization on the i r vMiimJ in g Basis of Innovativeness if waking in 413mg Ciemliy targemmema i mix i i Laggards 16 Vi ikaliccmwimt mam igmh ii 191 gm Fig rgwat im V W mime Mg whim 2 SD i SD Mean 1 SD R alq ggg quot Time to Adoption 8133 From Mean iii Mm Miami I W tdm gblwi Koro Reprinted With permission from Rogers21 x mgwi E1 3 Elma Wm g P ii 1EL FCEW BEE an 361 am ring growers minim is m zi EMF 5 fmm i win game Fol1mm ML in ammij iImryafmg in weailii girs 4mm aw wearm Mai Mm ii A Case Study Cholecystectomy Removal of the Gall Bladder Imgwi i r Right Left hepatic bile ducts to liver Cystic duct Common bile duct Common outlet or ducts E F1113 a my WEE D 7151ng E SW Emacer 1mm mm Exita mm 0965 mm mmpn gg mm mm mm a was arm am i al 1 Lu a 151 may vg w Q mgr ww w Cbmwnrgmx m a 7 Mg g QWEWE Ga H Hs fomes I Symptams II bfmgi k Ui i w cm I AbdeiInam dsmmfa t umn I Heartburn I Ind iigest an I Acute in amma m Gd Elodde JICmmmmmmm Stories Pancreatic Duc1 Treatment of Gallstones Before 1990 Open surgery to remove the gall bladder I Effective Low mortality rate 031500 7 day hospital stay 30 days lost time from work Most common nonobstetric surgical procedure in many countries A Case Study Laparoscoipic Cinoiecystectomy n Mast significant majgr surgicai advance at the 198 a singrter naspitaiizaticn a Rapid recgvery n Earriy return ta a Signi cant iinanciai savian n Farerunner i era 0i mininiaiiy invasive surgery Laparoscopic Remova of Gali B adder 1Fmt aVSgm mmx h 1Smmm n k m g mdg imVHmd mmii m2mmmmg VMQWQWEEngg Ed SwmW amp mamwmh bmbm 1TVmmMmk mgmwmmm g mga g g m mw hm 3PMKRMWE W HWNmm EW U g ElSwa M immmgmg mga d MgWmr ny 8i b UC Mdig fi wTEW dig i J lHHIV EaHlilbbddC Egg 1 S m M mmmgg mmmmwmmm mmMW mEW WHMmWWW w MmWamp aTW W W MMMM M WW SWW7 gmg wwmmmmmanmmmmgmmw W Laparoscopc Chol ecystecfomy AdvantagesDsadvantages Bene ts Equot 39 E quot39g g quot r7 3 iease r 1riiingy Ii iio incision gain as occurs with standard abdominai surgery a tip to 90 or patients go home the same day a Within severai days normai activities can be resumed in No scar on the abdomen Comipiications Cdmidiicadon about tor tinis igirdoediiune iior gaiiidiadder surgery 11 Nausea and vomiting may occur arter the surgery a injury to tire ibiie ducm biood vewis or intestine can occur requiring corrective surgery oi removed iaioardsdoiorD Standard onen alfodominai surgery tiren immediatei3r deformed Did this technology diffuse slowly or rapidly An Immmnt MEIme mm 3927323 mm diam mmmm a Tim a Rim 3 c3 madMU mmlnmm mummy mm mm mxdmml ammag ltf rr Wm Mbma mm W Vlt immigras mg m mn mmg w a n W D I Laparoscopic Appendectomy I 1985 Semm s techniques used to perform the world s rst laparoscopic appendectomy Said to reduce problem of adhesions formed during opens surgeries Pub i c Respomse e He s gene elbseuutellly crazy asked te enderge a brain seen by his ce ieeguee m ere im i tiemy greeted with ieugih ter end derisiem 7gtZ L W 9 f quot3 39 Mm3 Ts 397 2913 V 71 7 n 739 an 1 7 C9 J a 7 r a Wee unmewe 1m numemw weweeJ we V Wquot 639 3 53 759 a Wquot Jr 917 V j41quot vr39w fc g XQ t e MQV QED O mg gh QUE a m e Smrgeoms no reesen fe chang e we estebllmshed wer kmg methed nte e cemlp ex technicalll manner lPulec Respomse a Semm 1 mm AM my li t f Mb gh m times Qwi trmmc cimt ii hm mmgamgg mt meat le WW M Gynemtllogi 1 v 9 3mg gj 1f W I J have surgem envy is trying t0 enter mm genera Swgew m bdstelr hs operat am egg l Did this technology diffuse slowly or rapidly D iffus m f39 Lap Clhgli y US Hea thc ares F mcedures performed Iaparoscopically 1 2 Years Since Introduc on of Laparoscopic Cholecystedomy Dm fus m f Lap Chmlhy Relative Cholecystectomy Rates on o u o E on o m o o US Hea thcare5 Connec cuta Maryland7 n Madman9 0 VA 1 Years Since Introduc on of Laparoscopic Chole y y c slsc mm mmmmm m m39gl mnmw qi 39mxm missus Maw Diffusion No technique in modern times has become so popular as rapidly as laparoscopic cholecystectomy Semm Displayed an ability to push his ideas through despite skepticism and suspicion Without Semm the laparoscopic revolution may have been postponed by many years Diffuson of Lap Chko Di us am of Wapamscopic health care is um Snce its intraduc ran m 1989 I thf j1iF CrdMF pud y Ema V V quot w r39 w g caj I By 1992 apyamJngmcc Q c mt g in IMIEQHKCZEJIFFE wpw 1 it mg r0 Lb k 5 11 75 a HH dim 1m ymmgg 4jpwjt m Iincrea mega rate of Take Heme Messages a In meet mgs g a Financie incentives fer physicians and hesptallls ta use the precedure m uemced the rate f dmfmsmm m Introdmct39iom f epemscepic Chm a with m wife A we ngwa 7R Qweg m leg A w Hf r Q A rag Rm vw 7 pewremve muskmugmmy Heme MM mmkegsue cmmy Lecture 2 Glossary Sensitivity Probability that given disease patient tests positive Specificity Probability that given no disease patient tests negative IOM Institute of Medicine 1 A nonprofit organization chartered in 1970 as a component of the National Academy of Sciences for sciencebased advice on matters of biomedical science medicine and health Incidence Frequency of occurrence Prevalence The proportion of individuals in a population having a disease Mortality Death rate DALY Disability Adjusted Years 1 The sum of years of life lost due to premature death in a population and the years lost due to disability for incident cases of the health condition Per capita per person WTO World Trade Organization An international organization dealing with the global rules of trade between nations Its main function is to ensure that trade ows as smoothly predictably and freely as possible Asphyxia A condition in which an extreme decrease in the concentration of oxygen in the body accompanied by an increase in the concentration of carbon dioxide leads to loss of consciousness or death Hemorrhage Excessive discharge of blood from the blood vessels profuse bleeding PATH Progpam for Appropriate Technologies in Health an international nonprofit organization who s goal is to improve the health of people around the world by advancing technologies strengthening systems and encouraging healthy behaviors SARS Severe Acute Respiratory Syndrome a respiratory illness caused by a virus that exhibits symptoms similar to the u or pneumonia Sputum Matter coughed up and usually ejected from the mouth including saliva foreign material and substances such as mucus or phlegm from the respiratory tract Pemates Perinatal An infant specifically one between the twentyeighth week of gestation and the first week after birth Neonates Neonatal 1 A newborn infant specifically one less than four weeks old Partograph A tool to help in the management of labor and to identify when intervention is necessary it used to record all observations made on a woman in labor including a graph where dilation of the cervix is plotted Epithelium epithelial cells Membranous tissue composed of one or more layers of cells separated by very little intercellular substance and forming the covering of most internal and external surfaces of the body and its organs Osmosis Diffusion of uid through a semipermeable membrane from a solution with a low solute concentration to a solution with a higher solute concentration until there is an equal concentration of uid on both sides of the membrane Congenital Of or relating to a condition that is present at birth as a result of either heredity or environmental in uences a congenital heart defect Cystic Fibrosis A generalized disorder in which there is a widespread disfuntion of the exocrine glands characterized by signs of chronic pulmonary disease due to excess mucous production pancreatic deficiency and abnormally high levels of electrolytes in the sweat BME 301 Lecture Fifteen Outline The burden of heart disease The cardiovascular system How do heart attacks happen I How do we treat atherosclerosis Open heart surgery Angioplasty Stents What is heart failure How do we treat heart failure Heart transplant I Left ventricular assist devices Arti cial heart Ea y El Shartrr 3 Signs of Heart Attack Maday heart attacks Start stawty symptome may came an go Chest discomfart Meat heart trwahe temmtaht th the ehter at Cheat that rar mare thah tear mrhatea array aha tahheaa r hath Discomfort th other areas at the Upper body 13 rhthrdte path gtr dracamtart th ahe r hath arma the heat hath jam r etahrach of breath a tteh atahg with theet il reearhtarto Bat rt ah eater herare lretahrart Other symptams L m 1 May thetade hreahthg eat th eatd er tight hireaaeeheaa Heart Attack Video httpwwwheart1comattackquidantcf m Heart Attacks Diagnosis of Atherosclerosis Detecton of Atherosceross uni Gunman Wm 1 Heart Attacks Treatment of Atherosclerosis How Do We Treat Atherosclerosis CABG Garmar ariaw by ass mailing IiEAEIG Enronary Artery Bypass Graft Left Internal Mammary Artery Aorta Narrcminga in coronary artery Internal Mammary Artery I MA LIn 39 n W IK i L E xoon M p g 39 Laugf p Proced u re a Patient is prepped generai anesthesia a Cheat access is gained tinrpugii sternum m Graft vessei is retrieved m Exippse heart tlnrpugii pericardium m Divert nirpugi i neart iung machine a Step heart a insert grad a Return circuiatipn tp heart a Cipse incisipn HeartiLung Machne m The hearta umg machine H d y ifF mm 39Lih i bres rm thca a 13H g pwmpc by mmmh mcg idhmwgh am xoygm r a jmmg mdr Xygcam a Pw mp mm QM Lmltawtily bil i t Ema li dy 1 a gt twig Suwrg ga m Heart Lung Machine A heartlung machine circulates the blood if the bear is stopped HEART UN LARDlUl ULMUNAKY ISYlAbb ADRTIC CANMILA PERICARDIUM L 1 V39ENA CAVAL ixmmmmm amiimimwmg mmx Heart Lung Machine WWW Heart Lung Machine blood ow Want to mlmrmze RBC destrucuon hae Wymmamuwuamwmmmngw membrane bland membrane D E eC Veness 2W1 St m CABG precedtrres performed Precedure takes 6 hours 557 day hosptta l stay Grafts remem open amp turrettomrrg fer t etS yrs Risks 1 jHjleert Stmke li fisk m these ever 70 Hrj Sterrre metrrrd mreemm r symdreme e Qcturs few days to 6 merrttrs etter surgery e Symptoms are fever and chest pem v1 WW5 W H 39 derrty er rut72V ttr m39mrrg r r e emmg terse 771 C C Inmovafoms The titans gm Farmii 0000380 4 invxxxexxx 100i Onl39lnc radian wuuwmum comvoNlswclUDDEIVGSEUJHMY Closed Chest Coronary Artery Bypass on the Beating Heart 3200070350 June 8 2000 Utz Kappert MD Romuald Cichon MD Vassillos Guljelmos MD Joachim Nicolai MDZ A SemsMalle Tugiekln M39D Stephan Schueler MD PhD l Jens Schneider MD hm Schramm MD Germany Minimally invasive surgical procedures have become a part of routine cardiac surgery The surgical techniques have been developed for the treatment ot coionaly artery disease in order to minimize surgical trauma Wit the introduction of a seDehased totally endoscople imall irmslve cardiac cally functioning system into min Mic surgery further reduction of Skin incisions became possible and enhanced MIC techniques could in Improved Due to the 6 tree 39 m wrisrenhalited instruments and a newly developed endoe scopic stabilizer totally endoscopic coronary artery bypass procedures on a beating heart became teasible We present here our initial series of totally endoscopic Offrpulilp tering from coronary artery single vessel disease in all quot1H t p rmed via four 1 cm chest incisions as Elosedechest procedures Germany foulrpoint stab incision thus avoiding sternotomy and l 999 Falk 20001 After performing over izo minimally invasive surgical procedures since May law including a serle mammary arrery harvesting and totally endosro lc mice An initial series ot closedechest o wristeenhance robotic instruri 39 patlen s Suffering t39rom singievessel caionaiy artery dlsr ease ischDl using the left internal mammary artery LIMA is presented nch 37D gical Mountain VIEW CA has been described in detail before lcarpentier 1999 Falk 1999 Ldulmet 199w Three How Do We Treat Atherosclerosis Angioplasty admin lthynmwlamlm Hanm Human Geranium Balkan cath lar min unln a ta hallmark appmathas abslrumd amen in mm Wham bal lw as I n med IT breaks up amamsaialml Flaws Mar lumen wldmned hallnan camalar with d h mum is Withe i39 39h39l39l ALLODN ANGIDPLASTY 9 PTCA Effectiveness Cannot always successfully perform procedure Diffuse disease Total occlusion Calci ed disease Restenosis Occurs in 2554 of patients Usually occurs within 6 months How Do We Treat Atherosclerosis Stent Silents taiiygmwmig glam 39 a39i wmnrui i rvk Apia VHDW is a Cmmnary Stem Implanted A 510 i5 meunmci m a I V 39 39 39Wir39ik I 39 httpwwwinselchkardiokardiorehabbilderstentjp harmm 3911th The haIlncn Ls In ated and the 519 quotIt 5 expan tied r quotmyquot quotWmF quotxfsr muF quot nr w The hallmn n5 nmmwcd and tha 51m 5 rmplanter In 1he vessel hmgd amid cmrfn39p 9 min Cam cr n wmmmmmmmwmgramM mm Mumim1miDigimamnmlmm mwmiw mug uni ITEXQ Drug Eluting Stents httpwwwnprorcfeaturesfeatureDhD WfId 1452217 Comparison of RX Methods Hospital Stay CABG 47 days Angioplasty 12 days Stent 12 days Restenosis CABG 56 o usually after 5 years Angioplasty 2545 usually within 6 months Stent 1520 usually within 6 months Comparison of RX Methods Cost CABG 35000 Angioplasty 17000 I Stent 19000 Costeffectiveness Additive procedures Within 5 years 2040 of patients have second PTCA 25 have CABG Additive costs I 0 years per patient costs of PTCA 3050 those of CABG 1 year 5060 3 years 6080 gt3 years gt80 Moving Target Problem What Would You Do Angioplasty Stent CABG CostaEfrectiverress Therapy Patient Group per yr the saved tPA Past MI high risk 36dh tPA Acute MI Marge infarct 524de treatment started gt2 hears past Counsehrrg Smath 13Q0e3900 CABG Two vesset disease 9200a425 severe arrgrra Wrath W A rst UILUJAK amers if 4 qWYHFK Hammad M quotI are a 1 v a I V M gdh ii g h aaS g bgqbaat at3 92 Midst quot 39 MUM WDKEYL Prevention or Treatment httpwwwnvtimescom2004O32lheal th21HEARhtm Progression of Heart Disease High Blood Pressure Hi h Cholesterol Levels 9 Heart Failure Atherosclerosis Heart Attack Ischemia Assignments Due Next Time HW 7 Chapter 12 problems 3 7 8 10 Bioengineering amp World Health Lecture Three Review of Lecture Two Developing world Perinatal conditions Lower respiratory infections Diarrheal diseases Malaria Developed world Perinatal conditions Congenital anomalies Lower respiratory infections Unintentional injuries P NE PPE Leading Causes of Mortality Ages 1544 Developing World 1 HIVAIDS 2 Unintentional injuries 3 Cardiovascular diseases 4 Tuberculosis Developed World Unintentional injuries Cardiovascular diseases Cancer Self in icted injuries 94 Burden of HIVAIDS Worldwide 40 million people are living with HIVAIDS 20 million people have been killed by the disease I 2003 u 3 million deaths 5 million new HIV infections 23 of those with AIDS are in Africa 1 in 12 African adults has HIV AIDS AIDS has Reduced Life Expectancy Life expectancy at birth Wars 70 ED 50 4D 3D All subSaharan Africa 20 Botswana Nigeria 10 SnuthAfrica United Republic of Tanzania D 39 190 7539 195 3039 1980 85 fear 1985 90 I 1990 95 I 1995 00 I ZDUU OS I2005 1U I Burden of HIVAIDS United States 0812 million people have HIVAIDS prevalence 3000040000 new HIV infections per year incidence Annual cost to treat 15 billion Clinical Course of HIVAIDS HIV Infection Human Immunode ciency Virus Spread by sexual contact with infected person or sharing needles with infected person or by transmission from mother to child Starts with an acute infection u like symptoms Destroys a type of cell called CD4 lymphocytes These cells are a critical component of the immune system the body s way to ght infection Latent Period After the initial u like symptoms adults may not experience any symptoms for 10 years People can still spread the disease during the latent period AIDS Acquired Immune De ciency Syndrome Following the latent period the number of CD4 lymphocytes will reach a critically low level causing AIDS C LEVEIS Hf viral load and CD4 immune response I 4 3 call C urse of H m Flu like 5 m toms iiral load y p CD4 LIttle or no mmmyte 1 symptoms stIll 3 AIDS y Infectious a Kw If 9quot EVEP ax xk J if I I I I hiquot V5 Rahxx xquot HIV1 axpnsw39e quotR 2 j quot ixquot Ra quot if I 254 weeks I 8610 33am 253 years Latency Over AIDS Mule clinical swulrmne What is AIDS AIDS Immunologic dysregulation innapropriate response of immune system Opportunistic infections and cancers Infections and cancers that would not occur in a person with a normally functioning immune system Average patient with AIDS dies in 13 years Within 10 years of infection without treatment 50 of HIV patients develop AIDS 40 develop illness associated with HIV 510 o remain asymptomatic l E h phy3 i gy of Hi Pat r 7 7 1 5941 RNA 3 39120 Envelope g Envelnpe Fromm 3 Protein E I E 17 E Matrix Proteins Lipid 39 Membrane p24 Capsule Proteins Reverse Transcript Anatomy of the AIDS i lrusJ k h5 9117 Patholphvsjgtoqv 0t tiIVAIDS dc Inningm Huile and nanends main 39 him I Imm 39 0 Iii Rmm mu 3 pm 339 Dueling process f J F 39 7quot mh l g f r k Agar 1 ml RNA Vial DNA Prcmrus 39 m 39 I Viral mm 1quotquot 39 139 If a I 331 ru xfipl llll39fll kllS li39l mlnll r p IQ J Hl u39 I 397 i a 39 a r gt informalnn Vital Hum iilih39brs new mantel admin I Mammal lmrktmg if lei nihilism f1quot 39 I will n k 1tr F N n l quota mu ma W Wquot PMm K xK WAA Pquot x 7 39 quotMme mum an Xg H mm 5 X 7 39 quot mm 3 m 39Il39hmspt httpwwwrochecompagesfacets quot 4hivifecyce2jpg 3m host cell The HIV vtms ehtets cetts CD4 tymphemtes that are e Chittcet tempeheht at the bed y s tmmhhe system hee thstde the vthhs ever the eett s thtethet meehthelhy te mete memes Qt ttsett destteythg the cett th the presses HAART Treatments for HIVAIDS Highly Active Antiretroviral Therapy HAART Combination of three or more drugs HIV can rapidly mutate to quickly develop resistance to a single drug Resistance develops much more slowly to drug combinations Goal of HAART Reduce viral levels to undetectable levels Has reduced death rate I in US and Europe by 80 Before and after HAART Treatment HIVAIDS THE TREATMENT GAP Estimated worltdwtcte coverage with anttretrovira treatment end 2003 r 7 w to Coverage tIZT 5 100 D some 749 1 2593 499 g t 10 4249 9 6f 11 Less than 10 t No reports of people on Heatment htt wwwn ro tem lates sto sto h sto Id4724368 Unintentional Injuries More than 125 million people aged 1544 die as a result of unintentional injuries each year Major cause of disability Leading cause is road traf c injuries 500000 deaths per year in his age group n 90 of these deaths occur in developing countries US Burden of Disease Road Accidents Rates declining steadily Leading cause of potential years of life lost I 2004 42636 Americans killed 2788000 Americans injured Fatal accident rates gt4X higher for males than for females Motorcycles 40X higher death rate per mile traveled 39 of fatalities related to alcohol use Prevention Rd Accidents Legislation Speed Seat belts Car seats Air Bags Alcohol use Motorcycle helmets Engineering Restraints Safety standards Education Seat belts Car seats Air Bags Alcohol use Accident Physics Newton s 2nd Law Fma a initial velocitytime to come to rest I In a crash Car velocity slows to zero in a very short time so does the velocity of your body Generates large forces How can we reduce these forces Reduce initial velocity of impact Extend time that it takes passengers to come to rest Red MCI Excessive D f Ff ETA r QR 9 II2 HR n 1 bULQ CD U LJx ee i i M J LJJKE3 3LEF JQD I JJ mg Fwquot Li r r 1 E 1m iv Rx 7 1611 EMS M J e xxLeih i Initial IE CDCthI cemtxr ibutes h TI v WVJLJ39VL E A 7 CQLUJWM HE S QWKJC MmmmeS Probability 0f death 391 153 C112 5 m 53 4 4 60 3C Impact EDEEd kma l 1GB Slowed Driver Reaction Time I When drivers anticipate a crash they have time to brake and reduce initial velocity Factors which slow driver reaction time Alcohol use Cell phone use Poor visibility cahol Use a Aiceiidi impaired drivers have 17X increased risk dii beirig iri iatai crasii 11 Aicdirdi use increases risk mere iii yddriger d rivers E S Cumpton et 21L 2002 821 Moskowitz etal 84 I rash risk reslame to zero B ka 0 Et al 1964 FE Allsop 1966 83 0 001 003 003 004 005 006 00 008 000 01 Bleed alcohol concentraticjn ISAC in gx39dl Alcohol Related Deaths Video Clip included on ieacher resource CD Mobile Phone Use At any given daylight moment in US 10 of drivers are using a cell phone Cell phone use Increases driver reaction time by 0515 sections Risk of crash is 4X higher when using a mobile phone Same as driving with a BAC of 009 9 dl 3 states have banned use of hand held phones while driving Extending Time to Come to Rest Crumple zones Allow passengers additional time to decelerate Seat belts Keep occupants in the passenger compartment Stretch during impact Reduce risk of death in crash by 4060 when combined with seat belts reduce risk of serious and fatal injuries by 4065 I Chi Reduce risk of infant dath by 71 and toddler dath by 54 A K numu m m g 90 cu musical h nlh nu lUllLVJIETIAJuhgih39gi ldalg39l xmV r Helmet Laws Cardiovascular Diseases 768000 people aged 1544 die as a result of cardiovascular disease every year I Most common causes Ischemic heart disease 286000 deaths Cerebrovascular disease 159000 deaths Ischemic Heart Disease Epidemiology United States a 11 million people have coronary artery disease hardening and narrowing of arteries Causes more deaths disability and economic cost than any other illness Risk factors Positive family history Diabetes Hyperlipidemia High Cholesterol Hypertension High Blood Pressure Smoking Ischemic Heart Disease Pathogenesis Atherosclerosis Hardening and narrowing of the arteries due to build up of plaque When the coronary arteries become narrowed the supply of oxygen and nutrients to the heart is restricted This damages the heart Ussue Ischemi Usualliy made by lhlisieiy Physicai exam may ieveai either diserders a high Clhilt lieeiiiei v JLVV39 l 1 a taillight a Dia Testing 1 EKGl a a malai39iailiag hite heart dating exeirase l a tehiegiala hty a Xaray imaging at arteries C Heaht Disease lDf aghos lg S I The EKG hreaits clown each heartbeat mm a series of electrical waves three of the waves the P wave the HRS complex and the T wave are associated Wim the mane contractions The F wave reflects activity la the head39s upper chambers The QRS complex and T wave re ect activaty in the lower chambers limitsiiimvmeieesteemmatlawattageemscmmmhmm Ischemt c Heart Disease Treatment Medicat management a mge a mmaw gateway ra t a Wit 1mtameeae Ttame tm ma Cetzamaa Amgttaptlaetm a Mate an these in un t 2t Banach Ashamsalaroiic Named Iu men Coronary plaque of angry artery Ba loon whale mm unln atad balloon approaches obslrucmd am in anory Coronary anew byuass glafnwng ICABG Mar mmen wldened balm catheIeI with de ated balloon is withdrawn Cerebrovascular Disease Stroke Third leading cause of death in the US Causes of stroke Blood vessel supplying the brain is blocked Thrombosis clot in vessel Embolism clot breaks off and lodges in blood vessel in brain Vasoconstriction or spasm Venous collapse Cerebrovascular Disease Diagnosis History Exam Imaging 039 Scan Computed Tomography Scan I MRI Magnetic Resonance Imaging I CT MR Angiography Angiography refers to an image of the blood vessels created using MRI or CT CT image pointing to areas of brain damage due to stroke MRI image of brain following stroke httpwwwthwnlws tyhospiml cmxlwohellnhospitlm MR Angiography of brain l httpberradharvmdeduCmsmmume lmplhm Cerebrovascular Disease Treatment Thrombolysis f Break up blood clot f Rehabilitation Experimental Treatments Angioplasty Heparin and Coumadin Blood Thinners before Aspirin At right Xray image showing before and after treatment Tuberculosis 600000 people ages 1544 die each year from TB 2003 u 88 million new cases Growing 1 oyear 15 million deaths 98 of deaths occur in developing world Estimated that TB will kill 35 million people in next 20 years if situation does not change Tuberculosis Bacterial infection of the lungs caused by mycobacterium tuberculosis Drugs which cure TB were discovered in 19405 u If untreated results in death in 5 years in half of all cases Imageofmmbamum tuberculosis tubercle bacillus wqwquot vquot rquot woem Tuberculusis i Tuberculosis 13 of world s population is infected with TB Not all have active TB Most have latent TB Immune system has walled off bacilli with waxy coat a 510 of people with normal immune systems will go on to develop active TB Higher in people with compromised immune systems 10X higher in people with AIDS TB is leading cause of death among people with HIVAIDS httpwwwnororqrundownsseqmentDhDwfId1520699 Tuberculosis Symptoms Fever Night sweats Weight loss Weakness Coughs productive with bloody sputum Airborne transmission I Left untreated one person with active TB can infect 1015 people each year Tubercu osis Dmagmosms 1 Skin test 1 Serum test 1 1 CXR Chest XmRa y a mdeHcag m TB Tuberculosis Treatment Latent TB Treated with isoniazid antibiotic prevents development of active TB Active TB Can almost always be cured by taking several antibiotics in combination I Stay home for several weeks while contagious Take drugs for 6 months Tuberculosis Resistant TB Bacteria can develop resistance to drugs I Can develop if patients do not take all medicine Growing problem 425000 new cases per year I In Russia and China 14 of new cases are resistant Must be treated with special medicines Poorly supervised Treatment is worse than no Treatment Fighting Resistance Directly Observed Therapy Shortcourse DOTS A health care worker watches and helps as the patient swallows antiTB medicines in hisher presence DOTS shifts responsibility for cure from patient to health care system Requires political commitment accurate diagnosis quality drugs observation follow up DOTS works well in many developing countries Overlapping Epidemics Malaria and HIV For people with HIV especially pregnant women episodes of acute malaria are complicated and more serious TB and HIV TB is the leading killer of people with HIV In Africa half of all TB cases are associated with HIV Cancer 580000 people aged 1544 die every year due to cancer Cancer is a group of diseases characterized by uncontrolled cell growth Cancer cells usually form a tumor Cancer cells can spread from tumor to other sites in the body metastasis 2004 Estimated US Cancer Deaths Lung amp bronchus 32 23690 25 Lung amp bronchus Prostate 10 15 Breast Colon amp rectum 10 10 Colon amp rectum Pancreas 5 6 Ovary Leukemia 5 6 Pancreas NonHodgkin 4 4 Leukemia lymphoma 3 NonHodgkin Esophagus 4 lymphoma Liver8t intrahepatic 3 3 Uterine corpus U blle 30 2 Multiple myeloma nary 8 er 2 BrainONS 39 0 K39dney 3 A 24 All other sites All other sites 21 ONSOther nervous system Source American Cancer Society 2004 Cancer 2nd leading cause of death in US 1 of every 4 deaths is from cancer 5year survival rate 59 Annual costs 107 billion What is Cancer Tumor Abnormal mass of tissue Growth exceeds that of normal tissue Purposeless and preys on host Caused by a single cell that has incurred genetic damage Types of Tumors Benign not harmful Malignant harmful Only malignant tumors can spread Metastasize V 39 at WPquot I5 39 Biology of Tumor Growth Natural history of most cancers has 4 phases Malignant transformation in target cell Growth of transformed cells Local invasion Distant metastases Importance 0f Cancer Screening LENQACY giw L mmvE M yquot EDIEJQW E m a 61 4 F i 01 E Ql 4 l Local K 5L0 lt El Regional 5 o 4 392 wLO El Distant y a A Q 20 4 9 if I v 75 1 v f 7 Jkm M 3mm I U MDWE SW mm a Reafgiwm Bl hsmd w 090 0f cancer deaths are dune to metastas sg Burden of SelfIn icted Injuries 480000 people aged 1544 take their own lives each year Highest rate of completed suicides Men gt65 years old Highest rate of attempted suicides Men and women ages 2024 Risk Factors Associated with Suicide Psychiatric illness Affective substance abuse personality other mental disorders Other risk factors Social adjustment problems Serious medical illness Living alone Recent bereavement Personal history of suicide attempt or completion Divorce or separation Unemployment Screening and Prevention 5066 of all suicide victims visit physician lt1 month before event I 1040 in the preceding week Hard to identify who is at risk Direct questioning has low yield General questions about sleep disturbance depressed mood guilt and hopelessness Survey instruments aren t good at predicting what will happen Summary of Lecture Two Developing countries Leading causes of mortality ages 1544 Developing world 1 HIVAIDS 2 Road Accidents 3 Interpersonal violence Developed world 1 Road accidents 2 Self in icted injuries 3 Interpersonal violence Summary of Lecture 3 Developing World HIVAIDS Unintentional injuries Cardiovascular diseases Tuberculosis Developed World 1 Unintentional injuries 2 Cardiovascular diseases 3 Cancer 4 Self in icted injuries P NE Lecture 8 Glossary Bone Marrow The soft spongelike tissue in the center of most bones It produces white blood cells red blood cells and platelets Source httpwwwcancergovdictionary Clonal Expansion After a Tcell binds to an antigenMHC complex the TCell is activated and goes through a number of mitotic divisions This process is referred to as clonal expansion and greatly increases the number of TCells that recognize the antigen Source httpwwwdwm ksedutwbioactiveleamer43ch43c3 html Complement The complement system consists of a series of about 25 proteins that work to quotcomplemen quot the work of antibodies in destroying bacteria Complement also helps rid the body of antigenantibody complexes Complement proteins are the culprits that cause blood vessels to become dilated and leaky causing redness and swelling during an in ammatory response Source httpWWW cancer 39 Endocytosis Endocytosis is a process whereby cells absorb material molecules such as proteins from outside by engul ng it with their cell membrane It is used by all cells of the body because most substances important to them are polar and consist of big molecules and thus cannot pass through the hydrophobic plasma membrane The function of endocytosis is the opposite of exocytosis Source httpenwikipediaorgwikiEndocytosis In uenza In uenza commonly called quotthe uquot is caused by the in uenza virus which infects the respiratory tract nose throat lungs Unlike many other viral respiratory infections such as the common cold the u causes severe illness and lifethreatening complications in many people Source httpwwwcdcgov uaboquadisease htm Lyse To break up to disintegrate to effect lysis Source httpwwwbiologyonlineorgdictionaryLyse MHC Molecules At maturity MHC Major Histone Compatability molecules are anchored in the cell membrane where they display short polypeptides to T cells via the T cell receptors TCRs The polypeptides may be quotselfquot that is originating from a protein created by the organism itself or they may be foreign originating from bacteria viruses pollen etc The overarching design of the MHCTCR interaction is that T cells should ignore self peptides while reacting appropriately to the foreign peptides Source httpenWikipediaorgWikiMajorihistocompatibilityicomplex Pathogens Any disease producing microorganism Source httpWWWbiologyonlineorgdictionaryPathogen Phagocytosis The process by which a cell engulfs particles such as bacteria other microorganisms aged red blood cells foreign matter etc The principal phagocytes cells that can engage in phagocytosis include the neutrophils and monocytes types of white blood cells Source httpWWW medtermscomscrip mainartaspa1ticlekeyl7895 Plasma The liquid part of the blood and lymphatic uid which makes up about half of its volume Plasma is devoid of cells and unlike serum has not clotted Blood plasma contains antibodies and other proteins Sourcehttpvvvvvv medterm 39 39 A 39 4 4 Pluripotent Hematopoietic Stem cells PHSC are the precursor cells which give rise to all the blood cell types of both the myeloid and lymphoid lineages This includes monocytes and macrophages neutrophils basophils eosinophils Tcells B cells NKcells microglia erythrocytes red blood cells megakaryocytes eg platelets and dendritic cells As stem cells they are defined by their ability to form multiple cells types and their ability to selfrenew Source httpenvvikipediaorgWikiPluripotentialihemopoieticistemicell Prokaryote A unicellular organism lacking a nuclear membrane a discrete nucleus and other specialized compartments within the cell Bacteria and viruses are prokaryotes Source httpWWW medterm 39 39 l JW Bioengineering amp World Health Lecture Six Review of Lecture 7 Science Science is the human activity of seeking natural explanations for what we observe in the world around us Engineering Systematic design production and operation of technical systems to meet practical human needs under speci ed constraints Six steps of the engineering design method Q3 How can technology solve health care problems CSl Prevention of infectious disease Roadmap of CS 1 Science Organisms that cause disease Immunity Engineering How to make a vaccine Vaccines From idea to product Societal Impact Health and economics Ethics of clinical trials Developed worldDeveloping world Pathogens How They Cause Disease Types of Pathogens Bacteria I Bacteria Cells with membrane and cell wall usually I Can survive outside host I Can reproduce without a host a Can be killed or inhibited by antibiotics How do Bacteria Cause Disease Invade host Reproduce Produce toxins which disturb function of normal cells Types of Pathogens Viruses Viruses Nucleic acid core with protein envelope Use host intracellular machinery to reproduce Cannot be killed with antibiotics gt50 different viruses that can infect humans How do Viruses Cause Disease Virus invades host cell Binds to cell membrane receptors Endocytosis brings virus into cell Virus takes over cell Use viral nucleic acid and host cell resources to make new viral nucleic acid and proteins More virus is released from host cell VII US causes host cell to burst OR Viral particles bud from host cell surface V39 Virus particle Proteineoat 39 39 s New virus 39 particle DNA or RNA Capsomer 1 mphysimgy of Pat 17 Matrlx Proteins r 1 941 RNA 3 39129 Envelope i Emempe Froteln 395 Protein g I 3 3 Llpld 39 Membrane p24 Capsule Proteins Reverse Transcript Anatomy of the AIDS ifllrusJ Pathophys iollogy of HIVAIDS modal magma IIIhid mm mm mung rm p m II F Mg viral DE hm1mm pmm s v 1 f F Jquot My ViralFLNA Elia HA Prams If 7 Uimlunmtlm quot m m h Trumaripmu IIy In uxva lament lrulmriptum quotzgv u39tra mm 1 r 339 1quot mm llHm 7 x Milu ll ii Em munch whims fr 7 f 2 I f warm 2 H 11quot um HEHIEIIL39 quot W n lquot in furran Ion 39 I I v I I I 39I I 39 3quot 4K 5 nah i x 7 39 V Pmlaua Iridium an r E milm g quotx If 39 3 Fun1mm E m host cell Magnet Immunology Question Based on your understanding of the characteristics of bacteria and viruses identify which item best represents a bacterium a virus and be able to explain why you chose each Magnet Immunology Answer Bacteria Virus The Immune System How Are We Protected Against Pathogens Types of Imm wmiw lnvading virus ems Gut 4quot 4quot quot7 e Keep path e Km them if they get in a Three Meyer39s 0f iimmumii y g Pl39wieiiee 11 Emei te Immme AN emime e pe a Emmume Vertebrates Adaptive Immunity Types of Immunity Physical Barriers Skin 2 square meters Mucous Membranes 400 square meters Innate Immune System Produces general in ammatory response when pathogens penetrate physical barriers Adaptive Immune System Gan adapt to defend against any invader Important when innate immune system cannot defend against attack Provides immune system with memory mcm EmE Ememe m O Ewmm I wEmm a fn When Physical Barriers Fall I BIOOCI Plasma I CEIIS Red blood cells White blood cells Platelets All of these cells are made in bone marrow from blood stem cells i a Hat itiln d malts Platelels malice 1L3 a 1 m n Ham Anqro V Bood Ces N U T ph Lympmgm Mf phg Q D flt m 1 Em Edy aga mi mfw mg Innate Immune System Primarily effective against pathogens outside of cells Two main weapons I 1 Professional phagocytes Cells that eat stuff 2 The complement system Proteins that tag stuff for destruction Components of Innate Immune System I 1 Macrophages Sentinels that patrol periphery If they nd an invader they become activated If activated they I Send signals to recruit other immune system cells I Become vicious killers Present antigen to adaptive immune system more on this later Companemts t Innate Immune System a 2 Cemptememt pmtetme quotm grand r We cw U PT m tiJSgt ME 2gt H J W QM Q Q Q 2 s r r 7432 1 SUM f m Tetget them at deettuxettem by z a term Membrane Attack Cemptexee i 5quot Tait oa 5 1lt23r C TW quotW a Ll ma dg t t MU met H tm Uri Jr w What happens when you get a splinter What happens when you get a splinter Pathogen makes it past a physical barrier Symptoms In ammatory Response red swollen hot pus What causes these symptoms Innate immune system is kicking into gear I Usually innate immune system can take mmdk What happens when you get a splinter Macrophages eat bacteria on splinter Phagocytosis Click for video clip Produce chemicals which Increase local blood ow Redness I Heat Increase permeability of blood vessels Swelling Recruit other phagocytes to site of infection I Pus Epidemis Magnet Immunology Question Which magnet resembles a macrophage in your kit Magnet Immunology Answer Macrophage Adaptve Immune System Antigenbinding sites W TWO main components 5 Fight m mgmg MiEESiCdE ng 1 Antibodies 5 Fight mg dca aj lilga 2 Ki er T ceMs What is an antibody Binds to antigens foreign substance Binds to macrophage Antibodies How are antibodies made I B cells Lymphocytes that make antibodies Have B cell receptors on surface 100 million different types of B cells each with different surface receptors B cell receptors are so diverse they can recognize every organic molecule When a B cell binds antigen Proliferates In one week clone of 20000 identical 8 cells B cell Proliferation Secretes antibody Magnet Immunology Question Which components of your kit are most like antibodies Magnet Immunology Answer Antibodies Magnet Immunology Question Arrange the components of the kit to demonstrate how these antibodies bridge a pathogen and the tool to kill it Mag met Imm uxmollogy rHE E Bacteria with capsules must be coated with antibody before phagocytes can ingest them 1 r i psonin 7 Manmme mulecule r thugen r r 2quot 39 L 39k h 7 r Polysaccharide capau e Adaptive Immune System Con nuedquot How do we kill virus once inside the cell Antibodies cannot get to it I Need T cells n T Cells Three types of T Cells IGIler T Cells Cytotoxic T Lymphocytes Cl Ls Helper T Cells Regulatory T Cells How do T Cells ID Virus Infected Cells Antigen Presenting Cells All cells have MHC molecules on surface I When virus invades cell fragments of viral protein are loaded onto MHC proteins T Cells inspect MHC proteins and use this as a signal to identify infected cells Magnet Immunology Question Which magnet represents a normal host cell Which magnet represents an antigen presenting cell Using the components of the kit demonstrate the two steps required for viral antigens to be presented on the MHC complexes on the surface of the blood cell J a 39 1 1 a j k I 7 1 1 I 3 7 V r p VV39x 5 A rg H H 339 quot 197 39 r f w L P V L we NM ma FUEL GEN 1 1Lg w mun QQHH 1quotquotI 39 l W I r 1 Er l r a 39l I 3 l39 39 394 y 39y quot x5 x 4 L 4 Membrane 1 1 IT Nucleus 3 prutalns LVquot Macmphage Macrophage dlgaesls Ami npresenlll ng macrophage mlgen In lysosome dlsp an antigen tragmenls on surface receptors Magnet Immunology Question Which component resembles a Tcell Demonstrate how the T cell can identify a virus infected cell Mag met Imm unmoliogy Antigenpresenting e in s 0 Teen lymphocwe receptor Antigen fragment A A 4 e f i 1 Ag 7 Signal trgnsduction y quot n g m r 7 Antigenpresenting cell A T lymphocyte Immunologic Memory First time adaptive immune system is activated by an antigen Build up a clone of B cells and T cells Takes about a week After infection is over most die off I Some remain memory cells Second time adaptive immune system is activated by that antigen Memory cells are easier to activate Response is much faster no symptoms First exposure Clonai expansion Memory cells are Second exposure Stronger and more to antigen longelived continua to antigen rapid response to reproduce C j 9 p quot1 i if i m 3 U r u if r f 1 r i L r rquot r39 quot 39 39r39 n m r r O g r3 r 0 V 3 L Antigen 39 Q 5 I 11 1 j r 7 3 I r 39 x quot 7 J r Cquot 1 I Effector cellis carry cm immediate response Shanalived Primary response I I Secondary response Antibody concentration In plasma PRIMARY RESPONSE An body l l I l 1 2 3 4 gm News Antibody concentration in plasma SECONDARY RESPONSE 2 3 rm 39 Putting it all together Antigsn binds to antlbody 139 Actlvms B lymphomas quot33quot calls granulation Seclrete anuhudias l Wm P g goals 3 7 2 3 E33 r 1quot 39 Causes nmlgen I alum Eng and Acts a Enact vntmn of apaonlns bacterlal toxins Enhancad phagocytnsis a g m virus any lnvndal I g V m Mg x r Md nunan 3 If quot M micI quot Iannigm o 39 J lm mm 7 1 1 4 Unlan noel quotWquot nwl pmnlgll it a Helper l39cdl In A n R J Natural killer 7 cell 1 In 4 r s V nan k Kr 4 r F quot CYIUIJOIIO 4 395 Team B lymphocytes become Summary of Lecture 8 Pathogens Bacteria and Virus Levels of Immunity Barriers gt First line of defense Innate gt In ammation Phagocytes Complement Adaptive Immunologic memory Antibody mediated immunity Cell mediated immunity gt Pathogens within cells Diversity to recognize 100 million antigens Bioengineering amp World Health Lecture Thirteen ili iimi iii alumilieiii i A He is in a mitochondria B He is on a nucleus C He is on a chromosome 539 quotf m 13 W I quot7 iii 4 J V 2 K34 quot 4 7 J r SN y Mquot W quot mdcop 7 V mind Elm XE n A He is on a protein B He is on a gene a g chromosome gm w b 39 m mmu mm J x I uwmnnr 39 I A He g mmuu I C He is on fl some H is on DNA He is on a protein He is on u g w B C 7 5 239 393 39 um wumu B 1He I39S on a Esomal subunit u C Henson an actiVegggyme subun 1 x with I A He E n a quotquotquotY A My 5 a He is on DNA He is on RNA H w IB IC Microarray DVD Chapter 3 Four Questions I What are the major health problems worldwide Who pays to solve problems in health care I How can technology solve health care problems I How are health care technologies managed Two Case Studies Prevention of infectious disease HIVAIDS Early detection of cancer Cervical Cancer Ovarian Cancer Prostate Cancer Treatment of heart disease Atherosclerosis and heart attack Heart failure Technology Assessment The Big Picture where u immmns can 1quot Biological plausibility Technical Feasibility Science Drives Engineering Patient Outcomes Clinical Trials lscienti c Engineering Design Method Societal Outcomes How can we use science and technology to solve problems in health care How do we test and re ne innovations Three case39studies Treatment ofHeart Disease Early Detection ofCancer f Prevention Uflnfecmus DiSEaSe Precancer r CancerjsTransfonnatIon P M iPvr rg ismg YourHisk Factors I Your Noninfectious Risk Factors Litre Attenuated 1 Carrier The Circulatow System YDUF RiSk Factors Hrteriosclerosis CAEIG D eteo on of M39orohologieal Ch an ges Vaccines Heart Failure Transplant new Detech on ofMoleculer39changesa Irv W grievance to next unit Outline The burden of heart disease The cardiovascular system I How do heart attacks happen How do we treat atherosclerosis Open heart surgery Angioplasty I Stents What is heart failure I How do we treat heart failure Heart transplant Left ventricular assist devices Arti cial heart Burden of Heart Disease US and Worldwide Global BurdenCardiovascular Disease In 1999 Cardiovascular disease contributed to a third of global deaths I In 2003 n 167 million deaths due to cardiovascular disease By 2010 Cardiovascular disease is estimated to be the leading cause of death in developing countries 2002 orlldl 1de Morta W Mortality adults aged 1559 Mortality adults aged 60 Rank Cause Deaths 000 Rank Cause Deaths 000 1 HIWAIDS 2279 1 lschaemic heart disease 5825 2 lschaemic heart disease 1332 2 Cerebrouascular disease 11689 3 Tuberculosis 1036 3 Chronic obstructive pulmonary disease 2399 4 Roacl traffic injuries 814 1 Lower respiratory infections 1396 5 Cerebrouascular disease 7 83 5 Trachea bronchus lung cancers 928 6 Self inflicted injuries 672 6 Diabetes mellitus 754 2 Violence 173 2 Hypertensive heart disease 235 8 Eirrhosis of the liver 382 8 Stomach cancer 63935 9 Lower respiratorI infections 352 9 Tuberculosis 495 10 Chronic obstructive pulmonary disease 343 10 Colon and rectum cancers 47 Mortal I iii in Developing Coontjri Figure 61 Deaths attributable to 16 leading causes in developing countries 2001 es Cardiovascular diseases Malignant neoplasms Injuries Respiratory infections Chronic respiratory diseases H IWAI DS Perinatal conditions Diarrhoealcliseases I I Tuberculosis Digestive diseases 39 Childhood diseases Malaria Diabetes mellitus Loquot39 mortaitwdet39elminc countries Diseases of the genitourinarysystem I W L 39 l J l Highmortalityr developing countries Neuropsy chiatric disorders Maternal conditions I l l l l 6000 8000 10 000 Deaths 000 2000 1000 12 000 Burden of Cardiovascular Disease United States Cardiovascular Disease Affects 61 million Amerins almost 14 of population Accounts for more than 40 of all deaths 950000 Americans die of cardiovascular disease each year Two main forms of cardiovascular disease Ischemic heart disease I Stroke Ischemic Heart disease Leading cause of death in US Coronary heart disease is a leading cause of premature permanent disability among working adults Stroke Third leading cause of death in the US Cost of CVD disease 351 billion 209 billion for health care expenditures 142 billion for lost productivity from death and disability US Burden of Heart Attack Consequences of ischemic heart disease Caused by a narrowing of the coronary arteries that supply blood to the heart Often results in a heart attack Each year 11 million Americans suffer a heart attack 460000 of those heart attacks are fatal Half of those deaths occur within 1 hour of symptom onset before person reaches hospital Early Detection of Cardiovascular Disease Risk Factors Tobacco use Low levels of physical activity Inappropriate diet I High blood pressure Over 70 not under control I High cholesterol Over 80 not under control Screening for Cardiovascular Disease Measure blood pressure annually 1213 point reduction in blood pressure can reduce heart attacks by 21 Check cholesterol every 5 years n 10 dr0p in cholesterol can reduce heart attacks by 30 These With High Breed Pressure Percentage of Americans with Uncontrolled High Elleud Pressure by Race and Ethnicity 90 BU r0 7 e a x 60 50 40 k 30 20 x 13 African Mexieen quotquotu39hite Tetal US American An rerlcan Pepul anon Percent 24 Blood Pressure My blood pressure 10368 The higher systolic number represents the pressure while the heart is beating The lower diastolic number represents the pressure when the heart is resting between beats Normal blood pressure Varies from minute to minute Varies with changes in posture Should be lt 12080 mm Hg for an adult Prehypertension Blood pressure that stays between 12013980 89 Hypertension Blood pressure above 14090 mm Hg How Do We Measure Blood Pressure Sphygmomanometer Dr RRK wastes two minutes of class times and proves that you can nd anything on the intemet httpruIzofDunkfreefrvideosmanamanawmv Increase cuff pressure until it is higher than systolic pressure Blood ow into arm stops Gradually release pressure When cuff pressure systolic pressure Blood begins to ow again HsgyKorotkoff sound associated with turbulent ow through a When cuff pressure diastolic pressure Artery is no longer compressed No longer hear Korotkoff sound How Do We Measure Blood Pressure Cuff ressure gt12 mmHg 69 Cuff pressure beiween Stethoscope Cuff resaure so Rm Hg httpcwxprenhacomb ookbindpubbookssilverth orn2medialibImageBan kCH15FG1507ajpg Serum Cholesterol Levels Total LDL HDL Cholesterol Optimal under 100 above 60 Desirable under 200 under 130 Borderline 200239 130159 Abnormal over 240 over 160 below 35 LDL causes cholesterol to build up inside blood vessels HDL actually removes cholesterol from the walls of blood vessels and brings it back to the liver to be safely excreted The Cardiovascular System First ribcut Apexof heart The heart is on the ventral side of the 1horacic cavity sandwiched between the lungs Dlaphragm Mussels that carry wallaxygenaled bland are red mm wlth less walloxygenated blood are blue Fig 147 ad The Cardiovascular System Silverthorn 2nd Ed Superior Pulmonary cemllunar valve Superior vena cava Left ventricle Cusp at left blcuspldjvalve Flight ventricle Chantae Cusp of rightAV tendlneae trlcuspldjvalve muscles Left ventrlcle The ventrch occupy the bulk ofthe heart Thearterles andveins all attach to the base of the heart Onemayflowthmughtheheartlsensured by two sets at valves ngerx m m E j l ng M47 ru mwamlar Armin Velns Albanan m Superior van saw lrrlarlnr van cairn Hindu E M s w q 0 am mat mw 1 mm imukamrgy gamma wrywin 2W Quantifying Heart Performance Heart Rate HR Number of heart beats per minute Normal value is 6090 bpm at rest Stroke Volume SV Amount of blood pumped by ventricle with each heart beat Normal value is 6080 ml Cardiac output CO Total volume of blood pumped by ventricle per minute CO HR x SV Normal value is 48 Lmin Blood volume Total volume of blood in circulatory system Normal value is 5 L Total volume of blood is pumped through our heart each minute Quantifying Heart Performance Ejection Fraction EF Fraction of blood pumped out of ventricle relative to total volume at end diastole EF SVEDV Normal value gt 60 Measured using echocardiography Normal echocardiogram httDwwwkumcedukumcoedscardioloclvmoviesn llonqecholabeledhtml Dilated cardiomyopathy httDwwwkumcedukumcoedscardioloqvmoviess ssmoviesdicardiomvoossshtml Heart Attacks Pathophysiology Diagnosis Treatment Heart Attacks Pathophysiology 0A heart attack occurs when the quoturr supptytng the heart are Masked preventth axygen and nutrients from reachth the heart tissue otsahennta A Irestrtctton in b suprpty Heading to damage LuIt Main armW Mere LP IE imlm em knew mm ntr39rmr Bentham Mew Early Warning Signs of Heart Attack Many heart attacks start slowly symptoms may come and go Chest discomfort Most heart attacks involve discomfort in the center of the chest that lasts for more than a few minutes or goes away and comes back The discomfort can feel like uncomfortable pressure squeezing fullness or pain Discomfort in other areas of the upper body I Can include pain or discomfort in one or both arms the back neck jaw or stomach Shortness of breath Often comes along with chest discomfort But it also n occur before chest discomfort Other symptoms May include breaking out in a cold sweat nausea or light headedness Heart Attack Signs httpwwwnhlbinihqovactintimevideo htm How are Artettes Stocked Athemscemsts Foumatiozn of plaque within the arteries causing them to harden and narrow Cross section showing the inside of an artery and the build up of plaque http www pathoogyvcued ueducation card ioimagesldajpg The lumen is the open space in the artery Notice how it narrows with the build up of plaque I Atherosclerotic Artery What is Plaque oPlaque is made up of fatty substances cholesterol cellular waste products calcium and fibrin oThese materials are thrombogenic meaning they induce blood clot formation Blood clot formation blocks the artery causing a heart attack in the heart or stroke in the brain httpwwwamericanheartorgpresenterjhtmlidentifier228 galmg 39medlmagery39compatho Heart Attack Video httpwwwheartlcomattackCluidantcf m Heart Attacks Treatment of Acute Occlusion tPA Tissue Plasminogen Activator Tissue plasminogen activator tPA A thrombolytic agent can dissolve blood clots Approved for use in certain patients having heart attadlt or stroke Clinical Studies tPA and other clotdissolving agents can reduce the amount of damage to the heart muscle and save lives To be effective they must be given within a few hours after symptoms begin Administered through an intravenous IV line in the arm by hospital personnel Patients treated within 90 minutes after onset of chest pain are oneseventh as likely to die compared to patients who receive therapy after 90 minutes Heart Attacks Diagnosis of Atherosclerosis Above Fuoroscopy procedure Ftuoroscopy A procedure to which the patteht ts hjected with contrast agent and ptaced under ah xaray to produce an ahgtograph These images shew the arteries at the heart Arrews htghhght the pertteh at the artery that is htackedr e Dr Krked BME 301 Lecture Fourteen Four Questions I What are the major health problems worldwide Who pays to solve problems in health care How can technology solve health care problems How are health care technologies managed Two Case Studies Prevention of infectious disease HIVAIDS Early detection of cancer Cervical Cancer Ovarian Cancer Prostate Cancer Treatment of heart disease Atherosclerosis and heart attack Heart failure Outline The burden of heart disease The cardiovascular system How do heart attacks happen I How do we treat atherosclerosis Open heart surgery Angioplasty Stents What is heart failure How do we treat heart failure Heart transplant I Left ventricular assist devices Arti cial heart Burden of Heart Disease US and Worldwide Global BurdenCardiovascular Disease In 1999 CVD contributed to a third of global deaths In 2003 n 167 million deaths due to CVD By 2010 CVD is estimated to be the leading cause of death in developing countries m2 W dwmde M rta mty Monalily adults aged 15 59 Mortality 7 adults aged 60 2 n c Se Dead1x000 Rank Cause Demhs 000 HNmns 2279 7 xsz aerm eavtuseass Smaemm mart 752352 evemvasm ar wsease an n evm 0575 u 3 Guam nbstmdwe puhnnnary msease 2399 4 Read traf c Wun es m 4 Lawev vesphamry mfemans 7395 s arehmvascu ar Mm 783 5 Trarhea hmndws hmg ancevs 928 s Sewnnmed wunes 572 7 vmence 473 7 H enenswe heart msease 735 a when uf the Way 382 a Stumam mm 605 9 Luwenesmramw mfenmns 352 9 Tubevcu asxs A95 70 Chmmmbsuuztwe nu munavy Mm 343 70 man and 72mm anms 477 Figuve 51 Deaths attributable tn 15 leading causes in develnping muntries 1001 I avthuvasuavd59ase Ma mam neup asms Manes Respwatory mfemons hmmz vespvatmy mseases s Pennata andmuns Dwanhaea dwstases TuhEKu osis Dwgestwe mseases mama dwseases Ma ana Dwahe es me htus Dwseases at the gemtummavy system N Matema ondmuns 1 Luwnmnamy deve upmg munmes nghrmmtamy deve upmg aunmes 6000 Deaths mm 8000 m 000 United States CVD a meet 611 milliheh Ameheehe etnimegi39t We eff ligehuteitteh heve CMD a Aeeemte fer mete theh t eliH teeth a 3 The meth tehme th CW9 11 teehemte dteeeee f Shake techemtc Heart dtseese a Leedth eeee eeth h US a g 1pgtehnfmemeht epx1ty emehgg wethhg edh te Stroke 1 Ther Heeethg et deeth th the US of CVD dteeeeezz E 3 httteh I 209 hittth fer heetth care quot e 142 When her eet from deem and dteeibt ltty Us Burden of Heart Attack a Hermes 0f Escheth heart disease by rrarrerrrrrrg at the earerraray that surgery breast heart r a Each year m mitten 0 K 5 Ln W 7 r r 4691 n a tease Caesar wrtarm 11L hear at sirrasterth eras aerate reames aespirta Early Detection of CVD Risk Factors Tobacco use Low levels of physical activity Inappropriate diet High blood pressure Over 70 not under control I High cholesterol Over 80 not under control Screening for CVD Measure BP annually 1213 point reduction in blood pressure can reduce heart attacks by 21 Check cholesterol every 5 years n 10 drop in cholesterol can reduce heart attacks by 30 af x 7quot w x a i w H quot yquotquot W ith High Percentage of Americans with Uncentreiled High Blend Pressure by Race and Ethnicity 3990 BU E 3 xx gig 23 ke 13 Atrial1 i39v lexiean quotquotu39hite Tetal US An ierlrzan American Pepul atlen D Pressure My Mood pressure 10368 3 We higher sysitprr re member represepts the presspre wp e peeri peer pg a We U X p7 e1r39fli aS QWC member reprres rris the pressure when quotripe peert resprrg Normal lbll pressure a r39rpm rp ppre re mrppte 11 Verr with rp e Sheep be mm Hg fer ep epp39rt rPrehyperrensrorr 1 preps pressure eet hemveep Hypertension a greed eppwe mm rip How Do Measure BIP Sphygmomanometer a Dr RRK weetee itwe m preve335 yew em ee emymmg m the imtemet I 7 UH N 7 11 t mighe amen a M if preeew e Mmt FS UHT a B ood ow inmate arm stem 3 redwe y Jreeewre a When CW preesure e systemic pressure a Ii eee beg me e ew ege m a wee Kere ke f eewmd Wm immbtwlke i ew hwewgh ememy a When cuff pressure di este fm pireseure 11 me eager 1 We ewe 2 l39n eew Kem ike f eew e S gmu E C aura u pms mean I wandlzomm g y L 1 z s l f lt l i Serum Ciioiesteroi Leveis Teiiei LDL HiDL Opiimei under 100 above 60 Desiiaibie iiimeiei under 1 Bordieiiiiie iBQQiSQ Abnormai eiiei over 160 beiow 35 LDL caiisee ciioiesieioi i0 ibiiiidi up inside ibin HDL actuaiiy removes cineiesterol from the wails oi biood vessels and brings it back it tine livei to be safeiy excreted The Cardiovascular System Diaphragm The heart is on the ventral side oi the thoracic cavity sandwiched between the ungs mule that carry welloxygenmed bland an red Ihon wim lest weiloxyqanaiad blood are blue Fig M 7 ad rThe Cardiovascuiar System Siiverthom 2 Ed Fulmonlry mllum valve Left quotquotm mam nulmonnrv quot r IMI H c 39 fr r I 39 V 397 v cmleka 7 r blwlpldvllve chom Cupul rlghuv imamI Mcuwld39IVINI The venlrlcles occupy the bulk arm 5 nerlesandvelnsall anachloule baseufme heart ehunlumwed vul I Dmayllwlhmugmh in two mm htt wwwinnerbod com anim hearthtm LI l II thQ I II I I I I hfml Silverthorn 2quot Ed Fig 147 eh The Cardiovascular system Amman 5mm m cm mm nanmm mm mm m m pg 1417 Genera anatomy of me cwrcu atory system SHvenhom 2quotd Ed Quantifying Heart Performance Heart Rate HR Number of heart beats per minute Normal value is 6090 bpm at rest Stroke Volume 5V Amount of blood pumped by ventricle with each heart beat Normal value is 6080 ml Cardiac output C0 Total volume of blood pumped by ventricle per minute I CO HR X 5V Normal value is 48 Lmin Blood volume Total volume of blood in circulatory system Normal value is 5 L Total volume of blood is pumped through our heart each minute Quantifying Heart Performance I Ejection Fraction EF I Fraction of blood pumped out of ventricle relative to total volume at end diastole I EF SVEDV I Normal value gt 60 I Measured using echocardiography I Normal echocardiogram I Dilated cardiomyopathy Heart Attacks Pathophysiology Diagnosis Treatment Heart Attacks Pathophysiology Case Study Three months following his first visit to your office Mr Solomon presents to the ER in the early morning with chest pain of one hour duration Mr Solomon describes the pain as being severe and quotlike someone was sitting on his chestquot The pain located quotin the lower part of my breast bonequot awakened him from his sleep Although he tried to relieve the pain by changing positions in bed sitting up and drinking water it remained unchanged He did not sleep well because quotI had an upset stomach an acid burning feelingquot He attributed these symptoms to over eating and drinking at a Christmas party He has no pain or discomfort in his arms but says he has an quotachenessquot in his left jaw which he attributes to quotbad teethquot Physical examination reveals the patient to be anxious pale diaphoretic and in obvious discomfort He is unshaven and accompanied by his wife He tries to relieve his pain by belching He coughs occasionally Mr Solomon says quotthe flu has been going around the office and I ve had a little cough and fever all weekquot httpwwwmeddean luceduIumenmededmechcasescase2Casefhtm Ea y El Shartrr 3 Signs of Heart Attack Maday heart attacks Start stawty symptome may came an go Chest discomfart Meat heart trwahe temmtaht th the ehter at Cheat that rar mare thah tear mrhatea array aha tahheaa r hath Discomfort th other areas at the Upper body 13 rhthrdte path gtr dracamtart th ahe r hath arma the heat hath jam r etahrach of breath a tteh atahg with theet il reearhtarto Bat rt ah eater herare lretahrart Other symptams L m 1 May thetade hreahthg eat th eatd er tight hireaaeeheaa Heart Attack Signs httpwwwnhlbinihqovactintimevideo htm LuIl Main Emory M15 LizE I irnmfquothzx mm Lt interim DWEMIM Amew Lumen ARTERY Tunica media Tunica adventiiia http www pamo ogy vcu edueducanm cardwOwmagesld 3 pg