exam 2 341

• Classic Stable Angina (Exertional Angina or Angina of Effort)

  Myocardial oxygen demand increases during exercise but oxygen supply doesn't increase proportionally, leading to ischemia

  
• To correct classic stable angina

  1. Decrease oxygen demand

  2. Increase oxygen supply

  
• Chronic stable angina (Chronic CAD)


  Results from imbalance of oxygen demand and supply, treatment focuses on re establishing balance between oxygen demand and oxygen supply

  
• Acute coronary syndrome (ACS)


  Often caused by plaque rupture and thrombus formation which leads to sudden reduction of coronary blood flow, resulting in unstable angina or acute myocardial infarction (AMI)
• Variant angina; Prinzmetal's angina

  Occurs due to intense vasospasm in coronary arteries, in the absence of increased myocardial oxygen demand

  
• Wall stress


  Most important determinant of myocardial oxygen demand, directly related to intraventricular pressure and ventricular radius, inversely related to wall thickness

  
• Heart rate

  Determinant of myocardial oxygen demand

  
• Cardiac contractility


  Determinant of myocardial oxygen demand

  
• Preload


  The amount of blood going back to the heart, determined by venous tone
• Increasing preload


  Sends more blood to the heart, heart works harder to get rid of it, increases wall stress, increases oxygen demand
• Afterload


  Resistance to left ventricle ejection, determined by arteriolar tone
• Cardiac Output (CO)


  Volume of blood pumped out (ejected) by heart each minute, factors affecting it are stroke volume and heart rate

  
• Preload


  LV pressure when ventricle is filled, preload <15 mmHg represents Frank Starling Relation, preload beyond 15 mmHg is a plateau of performance
• Afterload


  Resistance to LV ejection presented by systemic vascular resistance (SVR)
• Coronary perfusion pressure (CPP)

  CPP = aortic diastolic pressure - LDVP, LDVP is left ventricle diastolic pressure (preload)

  
• Increasing preload


  Decreases CPP
• Increasing CPP


  Increases oxygen supply

  
• Hypotension


  Can reduce oxygen supply
• Diastolic filling time


  The time the heart spends in diastole, increasing it increases oxygen supply, depends on heart rate

  
• Bradycardia


  Increases diastolic filling time
• Tachycardia


  Decreases diastolic filling time
• Increasing diastolic filling time

  Increases preload, increases wall stress
• Contraction of smooth muscle cell

  Voltage gated Ca channel allows Ca into the cell, Ca binds with calmodulin to make complex, complex activates myosin light chain kinase (MLCK), MLCK phosphorylates myosin light chain, phosphorylated myosin light chain interacts with actin and causes contraction

  
• Nitrates/NO


  Increase cGMP, cGMP dephosphorylates myosin light chain and prevents interaction with actin, causing vasodilation

  
• Calcium channel blockers


  Block Ca channel, Ca can't come in so no contraction, causing vasodilation
• Beta 2 agonists


  Activate AC and increase cAMP, cAMP inactivates MLCK, causing vasodilation
• Potassium channel openers


  Open K channel, causes hyperpolarization, sends negative effect on Ca channel and closes Ca channel, causing vasodilation
• Atherosclerosis: Thickening & hardening of arteries; Endothelial cell injury, LDL & monocytes infiltration, macrophages, foam cells, & fatty streaks formation & transformation to plaques
• Classic stable angina or chronic CAD


  Results from an imbalance between myocardial oxygen demand and supply due to atherosclerosis, treatment focuses on reestablishing this balance

  
• Acute Coronary Syndromes (ACS)


  Most often caused by atherosclerotic plaque ruptures & thrombus formation, leading to sudden reductions in coronary blood flow and myocardial ischemia at rest, prolonged ischemia causes acute myocardial infarction (AMI)
• Variant angina


  Occurs in the absence of increased myocardial oxygen demand, atherosclerotic plaques are absent, and ischemia is caused mainly by intensive vasospasm
• Determinants of myocardial oxygen demand

  • Cardiac contractility
  • Heart rate
  • Wall stress

  
• Determinants of myocardial oxygen supply

  • Coronary perfusion pressure
  • Diastolic filling time

  
• Determinants of vascular tone

  • Ca entry
  • MLCK activation
  • Myosin-LC phosphorylation
  • Interaction of Myosin-LC-PO4 with actin

  
• Organic nitrates (NO donors), Beta adrenergic blocking agents, Calcium channel blockers

  All classes reduce oxygen demand by decreasing heart rate, decreasing contractility, decreasing ventricular volume, and decreasing blood pressure

  
• Nitroglycerin (Nitrostat, NitroMist)


  Moderately volatile organic nitrate

  
• Isosorbide dinitrate (Isordil)


  Solid organic nitrate

  
• Organic nitrates


  Able to release NO in vascular smooth muscle cells of target tissue, induce cross-tolerance

  
• Orally administered isosorbide dinitrate

  Absorbed rapidly from GI and undergoes extensive first-pass metabolism resulting in a variable bioavailability of roughly 25%
• Sublingual nitrate products

  Act faster and bypass the first-pass effect, resulting in a higher bioavailability