Ischemic Heart Disease

- formation of atheromas (plaque) which narrows (stenose) artery lumen
- results in ischemia and damage/necrosis to downstream organs

The response to injury hypothesis explains atherosclerotic plaque development as a chronic inflammatory response resulting from injury to the endothelial lining of the artery. --- chronic endothelial injury (see risk factors that contribute to endothelial damage) which results in endothelial dysfunction
- accumulation of lipoproteins in the vessel wall
- monocytes (macrophages) adhere to the endothelial lining and migration into intima
- platelet adhesion
- release of growth factors and cytokines which cause
- recruitment and migration of smooth muscle cells and fibroblasts into the endothelium.
- SMC proliferation and ECM production (e.g. collagen is produced.
- Macrophages also engulf lipid and cholesterol derived from the blood.

- smoking, hypertension, elevated blood cholesterol
- are preventable
- risk multiplied when 2 or 3 factors are present
- diabetes mellitus
- non-modifiable risk factors - age, gender (post-menopausal women), family history, ethnicity
- obesity, socioeconomic class, stress, elevated blood homocysteine level

- heart - causes angina, MI, chronic heart failure, sudden cardiac death
- brain - ischemic stroke
- extremities - claudication, gangrene
- kidneys - chronic kidney failure

- requires oxygen and nutrients
- recieves blood from coronary arteries originating from aorta
- left anterior descending branch, left circumflex branch, and right coronary artery are all susceptible to atherosclerosis
- begins in early 20s and is slowly progressive... eads to reduction in blood flow which can cause necrosis of heart muscle
- does not occur intil there is about 70% reduction in area of coronary artery lumen

- chest pain due to myocardial ischemia from atherosclerosis
- crushing, tightness, heaviness
- usually at least one coronary artery with severe stenosis, but vasospasm can also contribute
- insufficient duration and magnitude to result in necrosis of heart muscle
- exercise and stress can trigger it

- after 30-40 mins, it begins to die, results in MI
- precipitated by formation of thrombus on luminal surface of coronary artery plaque that causes occulsion of vessel

- thrombolytic drugs re-establish coronary blood flow and prevent/reduce infarction
- percutaneous transluminal coronary angioplasty (dilation by inflation of balloon catheter)
- coronary artery bypass surgery

- clinical symptoms (prolonged chest pain that radiates to jaw or left arm, nausea, sweating)
- changes in ECG - indicates muscle injury
- elevated levels of cardiac enzymes like troponins and cardiac muscle creatinine kinase - specific to heart muscle and leak into blood when heart muscle cells are injured and dying

- involve left ventricle
- affected area corresponds to territory supplied by narrowed coronary artery
- blockages of LAD result in anterior wall infarcts, LCA infarct lateral LV wall, RCA infarct psterior LV wall
- infarct size is variable, and prognosis is worse for larger lesions
- transmural - full thickness of wall
- subendocardial - inner half of wall
- infarcts heal by scarring (muscle doesn't regenerate)
- infarcted muscle is lost to heart
- healing starts with remval of dead muscle (digestive proteolytic and phagocytic action of neutrophils and macrophages)
- followed by fibroblast ingrowth which produces and lays down collagen - well developed after 2 months

- disturbances in electrical rhythm of heart

- if too much muscle is infarcted and remaining muscle can't meet demands of body, results in "back up" congestion of blood in lungs and inadequate forward flow (cardiogenic shock)

- smetimes infarcted zone ruptures, causing acute hemorrhage into sac around heart which then compresses heart (cardiac tamponade)
- almost always fatal

- inflammation of heart surface (either early or late complication

- end stage scar weakens and bulges, forming aneurysm of LV wall
- congestive heart failure