Pathophysiology of Coronary Artery Disease

Blood supply to the heart

Coronary Blood Flow: Constant Demand

Arteries & veins are located on the surface of the heart, lying within groves called sulci

Blood flows through coronaries during the RELAXATION phase (diastole) Why?

Primary Superficial ArteriesRight CoronaryRight Marginal

BranchLeft CoronaryLeft Anterior

DescendingLeft Circumflex

Areas of Coronary Artery Perfusion:LAD:LAD: Majority of the left

ventricle: Anterior/InferiorCircumflex (Cx):Circumflex (Cx): Inferior and

Posterior LVRCA: RCA: RV, Posterior and Septal

LCA

Circumflex

LAD

Right Marginal Branch

Rt. Marginal

RCA

Pathogenesis of Atherosclerosis

Step 1: Endothelial Injury

Location? coronaries, carotids, renal arteries, lower extremities

Tunica Intima damaged (How?)LDL Oxidation: Initiates

Inflammatory Process:Monocytes: Attracted and “glued”

to endothelium by “ELAMS” (endothelial-leukocyte adhesion molecules)

STEP 2: Inflammation gone HaywireMonocytes/Leukocytes enter the

Sub-endothelial space

Initiate Smooth Muscle Cell proliferation

Attract more LDL to create a “fatty streak”

Blood Clot

Normal Narrowed Occluded

Ouch!

LDL’s and AtherosclerosisLDL’s and Atherosclerosis

Oxidized LDLs act as a “free radical”, which induces endothelial injury inflammation begins

Some LDLs are removed by macrophages, but high LDLs will cause much injury

LDLs = accelerated atherosclerosis

SmoothMuscle

Vessel Lumen

Myocardial Oxygen SupplyMyocardial Oxygen Supply

Cardiac cells extract most of the oxygen delivered (high A-vO2 diff)

Thus additional oxygen can only be met by delivering more blood by the coronary arteries

A reduction in coronary artery lumen size attenuates blood flow

Degree of Occlusion & Degree of Occlusion & Blood FlowBlood Flow

25 50 75 100%

BloodFlow

Blood FlowBlood Flow

Big reduction beyond 75% occlusion

Severity of disease depends on # of occluded arteries

Also location of occlusion (left coronary vs apical)

Myocardial O2 demand Myocardial O2 demand (MVO(MVO22) depends on..) depends on.. Myocardial tension

(pressure x volume)Inotropic State (Measure?)Chronotropic state

(Measure?)Myocardial mass

Indirect measure of MVOIndirect measure of MVO22

Rate pressure product (a.k.a. double product, tension-time index)

Considers 2 of the MVO2 indices:HR X SBP

Good estimate of oxygen use by the heart.

Used to determine angina threshold

End Results of End Results of AtherosclerosisAtherosclerosis

Unstable Angina

Stable Angina

Acute Myocardial Infarction

Sudden Cardiac Death

Stable Angina

Angina occurs at a consistent and predictable level of MVO2

Reduced Coronary Blood FlowAlways exercise at an intensity

below the angina thresholdHow would you identify the angina

threshold?

Anginal SymptomsVaried: Chest pressure/heavinessBack, neck, shoulder acheDiaphoresisPallorDyspneaDoes it occur upon exertion?

Unstable Angina

Due in part to intra-coronary spasmThis reduces lumen diameterMay occur ANY time (unpredictable)

and at any work intensityTermed “Vasospastic” or

“Prinzmetal’s Angina”

Acute Myocardial InfarctionAcute Myocardial Infarction

Intra-lumenal thrombus formation

Thrombus lodges in coronary artery, stops blood flow

Cells downstream are starved of O2

Leads to tissue necrosis

LAD: Thrombosis

Area of Infarct

Sudden DeathSudden Death

May be due to the death of heart tissue from large vessel occlusion

or.. emboli (ischemia) induce ventricular arrhythmias that will kill

(i.e. ventricular fibrillation)

Infarction symptomsInfarction symptoms

Similar to angina: diaphoretic, pallor complexion, pain

Vomiting, dyspneaSymptoms are often ignored or

denied by the patientOdds of survival are greatest if they

get help within 1 hour

Complications of MIComplications of MICardiac Tamponade: Fluid

between pericardium/myocardiumPericarditis: Inflammation of the

pericardiumEmboli: From either MI thrombus

or atrial clots formed with atrial pooling

Most Common Most Common Complications:Complications:Congestive Heart Failure:

75% of MI’s experience overt CHF Fluid backs up…

25% of MI’s experience “compensated” CHF reduced perfusion to “vital organs”?

Dysrhythmias: The importance of ECG monitoring post-MI

Assignment:Assignment:

Read: “Cardiovascular disease and the endothelium”

Answer: How does understanding the mechanism of the disease (pathophysiology) improve prevention, detection and intervention strategies?