April 26 Lecture

Ahmed

Wall tension = pressure x radius
                               thickness

hypertrophy is adaptive in decreasing wall tension thus oxygen demand

Oxygen Supply

• coronary blood flow = most important in determining oxygen supply
• Q = P / R        
• Q factors
• vasodilation (hypoxia most important)  hypoxia has direct effect on vascular smooth muscle and increases adenosine and NO.
• neural factors (alpha and beta)
• autoregulation
• cardiac cycle timing - most Q during diastole for left coronary artery - most during systole for venous   (RCA has more flow during systole)

      review of anatomy of coronary arteries and veins.  Coronary dominance is determined by origin of the PDA (posterior descending artery).  85% of population is right corornary dominant (PDA comes from right coronary artery)

exertional chest pain may indicate a supply problem (exertion increases oxygen        demand)

Oxygen Supply

• arterial oxygen content   = Hb x 1.36* x SaO2  + (PaO2 x 0.003)      (*ml O2 per g Hb  - 1 mol of O2 can bind with 1 mole of Hb = 22,400ml/mole/16,800 g/mol)
• extraction very high for heart so little reserve for increasing O2 delivery. 

Treatment

1. increase supply

  nitrates - vasodilate  ( The hemodynamic effects of nitrates include relaxation of conduit arteries, increased arterial compliance, increased venous capacitance, dilation of collateral vessels in the myocardium - http://www.ncbi.nlm.nih.gov/pubmed/1449098)

Valenzuela

increasing demand (O2 consumption) causes increased supply (lower resistance)

autoregulation - best in heart, brain, and kidneys

angina pectoris - precipitated by exertion (increased demand)

• classic (effort)
• vasospastic (associated with atheromas)
• unstable (at rest)

reducing risk factors (http://www.webmd.com/diet/ornish-diet-what-it-is)

Nitrates operate primarily by reducing PRELOAD - dilating veins >>> arteries  - don't increase O2 supply but decrease O2 demand.

side effects - nitrates oxidize ferrous iron to ferric (methemoglobin) - treated with methylene blue.  [metHb has high affinity for cyanide,  higher than cytochrome oxidase.]

Cyanide poisoning from food.  The cassava plant is now the world's third largest source of low cost carbohydrates especially for populations in the humid tropics, with Africa as its largest center of production. It originated in Brazil, and it is now brought to the world, especially to the African continent and all parts of Southeast Asia as well as many parts in the US. It is the principal source of nutrition for about 600 million people or even more around the world. The toxin in cassava is called "linamarin". It is chemically similar to sugar but with a CN ion attached. When eaten raw, the human digestive system will convert this to cyanide poison. Just a few pieces of cassava roots contain a fatal dose of cyanide.

Nitrates should not be used for right heart MI because reduced preload will worsen condition.

Nitrates plus beta or calcium channel blockers when combined have all beneficial effects for CAD.

• calcium channel blockers - vasodilate

Primary Cardiovascular Actions of Nitrodilators (http://www.cvpharmacology.com/vasodilator/nitro.htm)

Systemic vasculature

• vasodilation
      (venous dilation > arterial dilation)
• decreased venous pressure
• decreased arterial pressure (small effect)

Cardiac

• reduced preload and afterload
      (decreased wall stress)
• decreased oxygen demand

Coronary

• prevents/reverses vasospasm
• vasodilation (primarily epicardial vessels)
• improves subendocardial perfusion
• increased oxygen delivery

2. decrease demand

• beta blockers - decrease contractility, heart rate, BP
• calcium channel blockers -  decrease contractility, heart rate, BP

Colleran

vulnerable plaque have thin fibrous cap

HDL scavenges excess cholesterol and returns it to liver

HMG CoA reductase is rate limiting step for LDL cholesterol synthesis  (inhibited by statins)