Regulation of coronary blood flow and mechanisms of CHD Flashcards
What causes the development of collateral vessels? What are 3 specific stimuli for their growth?
Epicardial stenosis
VEGF, bFGF and PDGF
Among the following, hat is the major deteminant of coronary blood flow? • Autoregulation • Wall tension • Metabolic factors • Neural regulation • Humoral regulation • Myogenic tone
Metabolic factors
What are 3 major determinants of myocardial oxygen consumption?
Contractility
Heart Rate
Wall Tension
What are 2 determinants of oxygen supply to the myocardium?
Coronary blood flow
Oxygen extraction
Where would wall stress be greater, the endocardium or epicardium?
Greater in the endocardium
Where would resting blood flow be greater, in the epicardium or endocardium?
Greater in the endocardium
What is the role of autoregulation in coronary blood flow?
Over a certain pressure, it ensures constant flow even as perfusion pressure changes
Where in the heart vasculature is the major site of changes in resistance?
Arterioles
What is the crux of myogenic regulation in the heart?
As the blood vessels stretch more, there is a greater increase in smooth muscle contraction
Alpha adrenergic stimulation of the heart occurs via stimulation of alpha 1 vs alpha 2 receptors. What is the effect of alpha 1 stimulation? What is the effect of alpha 2 stimulation? What is the overall effect of adrenergic stimulation on coronary blood flow?
Alpha 1 - Increased epicardial and resistance vessel tone
Alpha 2 - Increased release of nitric oxide
Modest decrease in coronary blood flow
Direct effects of beta adrenergic stimulation to the heart is mediated via _ receptors. What is the effect of this stimulation?
Beta 2
Decrease in epicardial and resistance vessel tone
Indirect effects of beta adrenergic stimulation to the heart is mediated via _ receptors. What is the effect of this stimulation? (3)
Beta 1
Increased HR, contractility and myocardial O2 consumption
What is the net effect of beta adrenergic stimulation on coronary blood flow?
Increased blood flow
What is the direct effect of parasymp stimulation to the heart? What about indirect? (3)
Direct - Decrease in epicardial and resistance vessel tone
Indirect - Decreased HR, arterial blood pressure and myocardial O2 consumption
What is the net effect of parasympathetic stimulation on coronary blood flow?
Decreased blood flow
What is the effect of reactive oxygen species on nitric oxide levels? What is the net effect on vascular tone?
Use up (decrease) NO Block relaxation mediated by NO
How do all of the following affect levels of nitric oxide? What might counter these effects? • Atherosclerosis • Diabetes • Hypertension • Angiotensin II • Inflammation
All reduce levels of NO
Countered by antioxidants
What are 3 antioxidants referenced in the notes?
Vit E
Vit C
SOD/catalase
What are the 2 factors that determine contractile function of smooth muscle?
- intracellular calcium concentration
- sensitivity of contractile proteins to calcium
Regarding smooth muscle function, phosphorylated myosin light chain leads to _, while dephosphorylated myosin light chain kinase leads to _. What are the 2 enzymes that mediate this change in phosphorylation state?
Contraction
Relaxation
myosin light chain phosphatase
myosin light chain kinase
What is a negative regulator of myosin light chain phosphatase? What is the drug that targets this negative regulator? Activity of the phosphatase leads to [relaxation / contraction] of smooth muscle?
Rho kinase
Fasudil
Relaxation
What is a disease state where the activity of rho kinase is elevated?
Cardiovascular disease
What are 2 factors / events that can lead to angina pectoris in CHD?
Coronary artery stenosis following plaque formation
Vasospasm
Fixed atherosclerotic lesions is associated with what type of angina?
Chronic stable angina (exertional or typical)
