Stable ischemic disease part 3 Flashcards
Coronary blood flow is automatically regulated to meet metabolic demand
Thus, coronary arterial blood flow must increase to match myocardial oxygen demand.
The coronary arteries accomplish this feat by means of changing their vascular resistance.
During exercise, coronary blood flow can increase several-fold.
Metabolic byproducts–>Vasoactive mediators of coronary circulation
increase cellular metabolism
increase oxygen consumption
decrease ATP
metabolic byproducts
increase adenosine
increase CO2
increase Lactate
increase H+
Increase ROS
increase smooth muscle cell relaxation
increase vasodilation
increase coronary blood flow
Mechanisms of coronary blood flow autoregulation
Metabolic substrates and byproducts are thought to act as vasoactive mediators in coronary circulation.
Multiple agents are considered important, including adenosine, O2, CO2, lactate, pH (H+), and potassium ions.
ATP-sensitive potassium channels also open in response to decreased ATP, resulting in smooth muscle membrane hyperpolarization and thus relaxation.
ATP-sensitive potassium channels (KATP) in smooth muscle cells
Inside becomes more negative
Hyperpolarization
Harder to fire action potential
Smooth muscle contraction
ATP—>Adenosine—>Vasodilation
**A2 adenosine receptor activation **(Gs-coupled GPCR) in vascular smooth muscle
increase cAMP
increase KATP channel (ATP-sensitive K+ channel)
increase K+ conductance (positive charged lost to outside) (and Ca2+ channel activity)
Inner side of the membrane becomes more negative
Hyperpolarization
Other influences on coronary blood flow
Autonomic nervous system (ANS)
a1-adrenergic receptor activation
stimulates vasoconstriction
b-adrenergic receptor activation produces vasodilation
Muscarinic receptor stimulation produces coronary vasodilation
Various pharmacological agents with coronary vasoactive properties include:
Vasodilators (e.g., adenosine, nitroglycerin, dipyridamole)
Vasoconstrictors (e.g., vasopressin, COX inhibitors)
Adaptations to ischemic heart disease (IHD)
Dilation of coronary arteries & arterioles
Collateral vessel formation & remodeling
Ischemic “pre-conditioning”
Ischemic “Pre-conditioning”
A brief period of ischemia (2-5 min) prior to longer duration of ischemia
decrease Infarct size
decrease Ventricular arrythmias
Previous) Episodes of (non-lethal) ischemia (“Pre-conditioning”)
Remarkable increase in resistance to ischemic injury following ischemic episodes (e.g., angina pectoris, MI) decrease Severity
decrease Mortality (in-hospital)
To balloon or not to balloon for SIHD?Study results
Conclusion: No difference
No benefit of PCI
Pharmacotherapy alone is sufficient
Correlation between plaque regression/progression and achieved LDL-C
decrease LDL-C level achieved
increase Plaque size reduction
Prinzmetal Vasospastic Angina
Variant angina
Caused by vasospasm of coronary artery
Drugs for SIHD decrease oxygen demand and increase oxygen supply
treats cardiac ischemia (stable IHD), disease progression
Drugs for Angina Pectoris
Nitrates & Nitrites
Calcium channel blockers (CCBs)
Beta blockers
Nitrates and Nitrites
Nitroglycerin
Isosorbide dinitrate
Amyl nitrite
