Influence of Ischemic Preconditioning on Lethal Cell Injury after Coronary Artery Occlusion

Ryu, Kyu Hyung; Lee, Myoung Mook; Lee, Yung; Kim, June Soo; Seo, Jung Don; Lee, Young Woo

Abstract

BACKGROUND
The concept of myocardial injury after coronary occlusion is changing in recent years. Brief episode of ischemial induces reversible myocardial injury and repeated brief ischemic insults might cause myocardial necrosis due to cummulative damages. Recent observations showed that brief episodes of ischemia have protective effects on the myocardium increasing the myocardial tolerance to a subsequent sustained ischemic insult. This phenomenon is termed ischemic preconditioning and can be noticed after a variety of protocols in multiple species of experimental animals. This study was planned to 1) measure the changes of hemodynamic parameters and the ischemic damage of insulted myocardium during ischemic preconditioning, and 2) compare the infarct sizes with or without preconditioning.
METHODS
Using canine model of a single 90 minutes' occlusion of left anterior descending coronary artery and 240 minutes' reperfusion, 14 mongrel dogs were randomized to with(n=7) or without(n=7) ischemic preconditioning such as four 5 minutes' occlusion and 5 minutes' reperfusion, Changes of hemodynamic parameters and extents of the ischemic myocardial damages during preconditioning were observed. And using in vitro myocardial staining with monastral blue and triphenyl tetrazolium chloride, we compared the infarct sizes and risk areas in two groups of occlusion and reperfusion canine model with and without preconditioning.
RESULTS
1) Heart rate was significantly decreased after first 5 minutes' occlusion compared with those of basal control(151+/-27 VS 163+/-25 BPM, p<0.05) without further changes in subsequent ischemic insults. Left ventricular systolic pressure was significantly decreased after first 5 minutes' occlusion(109.0+/-19.9 VS 130.6+/-23.3mmHg, p<0.005), and after first 5 minutes' reperfusion and second 5 minutes' occlusion compared with those of basal control(111.3+/-29.8, 109.9+/-17.2 VS 130.6+/-23.3mmHg respectively, p<0.05), without further changes during remaining ischemia. Left ventricular end diastolic pressure and maximum +dp/dt were not changed. Peak -dp/dt was decreased significantly after first and second 5 min occlusion(943.7+/-294.4, and 962.1+/-281.5) from basal control level(1168.2+/-358.8mmHg, p<0.05). Thereafter no change was noted during remaining preconditioning. The changes in rate-pressure product were same as those of left ventricular systolic pressure(first 5 minutes occlusion ; 17.3+/-3.7 VS 21.2+/-3.5, p<0.005, second 5 minutes' occlusion ; 17.9+/-5.3, 18.1+/-3.4 VS 21.2+/-3.5, p<0.05). 2)Transmyocardial lactate extraction ratio was significantly decreased in early phase of ischemic preconditioning(17.5+/-11.3 VS 25.2+/-9.9%, p<0.05). 3) Hemodynamic parameters such as heart rate, left ventricular systolic pressure, left ventricular end-diastolic pressure, maximum +dp/dt, peak -dp/dt and rate-pressure product were changed similarly in both control and precontioned groups. 4) There was no significant difference of mean myocardial blood flows in infarct zones, which represent collateral blood flow, after 5 minutes' brief occlusion and 60 minutes of sustained occlusion in preconditioned group. 5) The infarct area/risk area ratio was significantly reduced in preconditioned group(27.0+/-9.6 VS 5.6+/-3.1%, p<0.005), but the risk area/left ventricular area ratio showed no difference in the two groups.
CONCLUSIONS
These findings suggest that, in the early phase of brief repeated occlusion and reperfusion, myocardial ischemic damage accompaning systolic and diastolic myocardial dysfuctions develops and myocardial protective effect of ischemic preconditioning was obtained at the same time. Ischemic preconditioning group demonstrated reduced infarct sizes compared to those of control group after 90 minutes' sustained ischemia and reperfusion in canine acute myocardial infarction model.