Protection of regional mechanics and mitochondrial oxidative phosphorylation by amlodipine in transiently ischemic myocardium.

The effects of amlodipine (0.3 mg/kg administered intravenously, n = 5) and placebo (n = 5) on recovery of myocardial function and respiration of isolated mitochondria were examined in "stunned" myocardium of normotensive pentobarbital-anesthetized dogs. Measures of myocardial wall motion, using sonomicrometers, and tissue blood flow, by radioactive microspheres, were obtained at baseline, 15 minutes after administration of amlodipine or placebo, after 10 minutes of left circumflex artery ligation and at 60 minutes of reperfusion. Mean aortic pressure decreased from 115 +/- 6 to 101 +/- 5 mm Hg after administration of amlodipine and remained decreased throughout the experiment. Heart rate was not significantly affected at any time. Both groups showed similar degrees of ischemia: elevation of ST segment to 4.7 +/- 1.4 vs 6.2 +/- 1.9 mV; reduction of ischemic zone shortening fraction to 0.6 +/- 1.9 vs -3.4 +/- 2.7%; and reduction of epicardial and endocardial blood flows (epicardial = 40 +/- 13 vs 43 +/- 13 ml/100 g/min; endocardial = 7 +/- 4 vs 13 +/- 6 ml/100 g/min [values for amlodipine vs placebo]). Mitochondrial state 3 rate of respiration and respiratory control index indicative of rate of adenosine triphosphate synthesis and membrane integrity in myocardial samples taken after 10 minutes of ischemia were significantly reduced in the placebo but not in the amlodipine group. Myocardial function showed significantly greater improvement in amlodipine vs placebo at 60 minutes of reperfusion as indicated by shortening fraction (17.7 +/- -1.4 vs 5.8 +/- -3.5%, amlodipine vs placebo), which may have been related to increased myocardial blood flow and decreased blood pressure during reperfusion. Thus, amlodipine pretreatment prevented mitochondrial dysfunction during ischemia and accelerated recovery of both myocardial mechanical function and blood flow when compared with placebo.

RCT Entities:   Population Interventions Outcomes