- coronary artery disease
- acute coronary syndrome
- coronary heart disease
- due to atherosclerotic plaque build up inside coronary artery, narrowing vessels and stiffens them, partial occlusion
- heart attack when plaque ruptures and forms blood clot blocking BF to heart, sub cat of CHD, can be asymptomatic (slient), symptoms are myocardial infarction, >75% occlusion
- aka ischemic heart disease, blockage in the coronary vessels prevents O2 from reaching the myocardium, results from CAD and can be asymptomatic
atherosclerosis and arteriosclerosis
arteriosclerosis is hardening and loss of elasticity of the arteries; atherosclerosis is hardening of an artery due to dev of atheromatous plaque, the pathological process underlying IHD
pathogenesis of atherosclerosis
1. formation of plaque
2. fatty streak
3. fibrous plaque
4. complicated lesion
- injury to endothelial cells causes them to become inflamed, produce cytokines and growth factors attracting immune cells and fibroblasts, LDLs can pass through endothelial cells and accumulate in the tunica intima
- sub endothelial LDLs become oxidized and produce reactive O2 species which signal endothelium to recruit monocytes which migrate to the tunica intima, forming a lesion; monocytes differentiate into macrophages, produce inflammatory signals (feed back loop for more monocytes) to prevent smooth muscle vascular control and consume oxidized LDL and turn into foam cells, gen fatty streak
- vascular smooth muscle cells (synthesize structural proteins such as collagen, elastin, and proteoglycans) proliferate and migrate on top of foam cells forming fibrous cap over lipid core to prevent fatty streak from leaking into blood
- overtime smooth muscle becomes stressed, releases senescence associated secretory phenotype signals to increase inflammation, resulting in cell death and necrosis within fibrous plaque; fibrous cap fractures, can no longer maintain lipid core, ruptures into blood, interacting coagulatory comp of platelets forming a thrombus (clot), greater than 75% impedance leads MI
- sometimes smooth muscle recreate fibrous cap with thrombus inside to prevent it from entering circ forming buried cap
stable angina pectoris
chest pain or tightening due to gradual narrowing and hardening of arteries which also dev ischemia, chronic endothelial cell dysfunction, decreased vasodilation, lactic acidosis, and abnormal stretch of ischemic myocardium; can be transient ischemia and asymptomatic (slient)
assessing and diagnosising
1. myocardial infraction
2. atherosclerosis
- diagnosis of MI is symptoms of ischemia using 12 lead ECG or cardiac angiogram or cardiac biomarkers (sig cardiac necrosis releases cardiac troponin, assessing amt of troponin indicates severity)
- measure carotid intima media thickness using ultrasound to determine amount of plaque; carotid plaque is a good determinant of coronary plaque; a more invasive method uses father with CMUT array with a guide wire to conduct intravascular ultrasound to gen 3D model of BV
chronic therapeutic interventions for heart disease: cardiac catherization and angioplasty
surgical procedure using catheter from femoral to affected artery to remove plaque and deploy angioplasty and stent to push plaque to side and increase BF, new tech has stent that can release medication
chronic therapeutic interventions for heart disease: coronary artery bypass graft
take artery or vein from other part of body and create a direct connection between aorta and atria to bypass blockage for direct BF
chronic therapeutic interventions for heart disease: beta blockers
blocks sympathetic neurotransmitters by competing for B1 receptor binding sites at SA node to prevent increases in HR (HR not a good measure of intensity), which prevents increase in BP and thus bursting of plaque to prevent MI
acute therapeutic interventions for heart disease: nitroglycerin
- quick acting spray, sublingual tablet, or IV
- converted by mtALDH into NO to drive relaxation of vascular smooth muscle to decrease cardiac pre-load and afterload to decrease vascular res and sys and dia BP
acute therapeutic interventions for heart disease: clot busters
- intravenous injection of tissue-type plasminogen activator (tPA)
- converts plasminogen to plasmin which breaks down fibrin (holds platelets together) to break up thrombus (clot) to increase BF
- PAI will eventually deactivate and liver will degrade and clear it; best taken during MI
importance of coronary BF and how much stenosis affects BF
- the heart extracts 70-80% of O2 from the blood at rest but during exercise cannot increase O2 extraction beyond 80 so all O2 is from increased BF
- healthy coronary artery can deliver 3-5 times more blood to the heart than at rest thus have high coronary flow reserve, little obstruction have little impact on flow but past 60% obstruction, greatly reduces flow increases chance of angina, MI, and death
PA and CAD
1. overview
2. functional changes
3. morphological changes
- risk of developing CAD decreases with increased PA but only small amount of PA is req to reap most of the benefits
- endothelium exposure to shear stress increases abiity of arteries to synthesize NO for vasodilation and inhibit plaque progression by reducing inflammatory cascade, increase HDL, increasse antioxidant def
- repeated shear stress promotes angiogenesis which increases branching from existing vessels to form collaterals due to hypoxic adaptation, increase alt pathways of BF and larger arterial supply
CAD and exercise capacity
- increased demand for BF req increased HR but also increase heart’s O2 demand
- myocardial O2 demand rep by rate-pressure product (HR x SBP)
- during exercise CAD narrow coronary arteries limit BF to myocardium causing ischemia (threshold when supply < demand) since extraction cannot increase but BF limited, hard to do exercise beyond low work rate ADL
coronary angioplasty v. exercise in stable CAD
- coronary angioplasty reduces stenosis by inserting a stent to push plaque away, the partial return of stenosis after 12 months, increased ischemic threshold, other variables constant
- exercise does not change stenosis or artery diameter over 12 months but decreases resting HR, increases maxHR, ischemic threshold, VO2 max, and phys work capacity
- exercise is superior in event-free survival and increased exercise capacity and is lower cost to healthcare providers due to lower risk of re-hospitalization and further surgery
coagulation and fibrinolysis during exercise
- after moderate intensity, fibrinolysis increases greatly to break up clots but during high intensity high amounts of shear stress to endothelial tissue causes physical damage and increases coagulation instead
- need to build up response to exercise or coagulation becomes too high
considerations and guidelines for exercise prescription in CAD
- previous conditions or risk of conditions, medications, significant reductions in exercise capacity
- after acute event, daily walking after discharge and supplement with PA during daily lifestyle, 30-60 min mod intensity aerobic on most days of week, for lower tolerance use multiple short bouts and increase with tolerance; upper body ROM (promote release of NO near heart) resistance training for 2-3 days 3-4 weeks after surgery
warm-up angina
- immediate ischemic angina after starting exercise bc stress to heart
- do long slow warmup bout of exercise to release NO then stop and allow the heart time to vasodilate, can complete second bout without symptoms or only minor symptoms of angina
2 ways that exercise treats CAD
- reduces cardiac O2 demand (rate pressure product = HR x SBP) since with exercise decreases resting HR with increased vagal activity and increased SV and decreases SBP by decreasing SNA and improving endothelial function to increase baroreflex sensitivity and ischemic threshold thus no longer ischemic during ADLs
- increases myocardial perfusion due to collaterals, greater capiliarization, slowing or regressing stenosis, and partial correction of endothelial dysfunction
