Hirohisa Arata

Ultrastructural and biochemical studies of ischemic preconditioning using an adenosine receptor blocker and an ATP-sensitive K channel opener

The effect of preconditioning (PC) on acute ischemic myocardial injury was investigated in an openchest dog model. Preconditioned dogs received four 5-min occlusions of the left anterior descending coronary artery (LAD), each separated by 10 min of reperfusion. Four groups were used to assess the effect: non-PC group (G-1), PC group (G-2), 8-phenyltheophylline-(adenosine receptor blocker) infused PC group (G-3), and nicorandil- (ATP-sensitive K-channel opener) infused PC group (G-4). The LAD was occluded for 60 min, followed by 60 min of reperfusion in all dogs. The rate of ultrastructural myocardial severe injury was 26% in G-1, 0% in G-2, 5% in G-3, and 0% in G-4. Biochemical analayses also indicated higher values of myocardial contractile function in G-2 and G-4 than G-1 and G-3. These data suggest that the adenosine receptor and K channel may play a key role in PC.

Pathophysiological Behavior of the Myocardium in Acute Ischemia and Reperfusion, with Special Emphasis on the Sarcoplasmic Reticulum

The myocardium under severe ischemia and reperfusion exhibits four types of different pathophysiologic behaviors: coagulation necrosis, stunning, ischemic preconditioning, and reperfusion injury. This chapter describes these changes in the postischemic myocardium in relation to the length of ischemia. Canine hearts were made ischemic by occludmg the left anterior descending coronary artery (LAD), and the sarcoplasmic reticulum (SR) from the ischemia-reperfused myocardium was analyzed. In permanent occlusion of the LAD, Ca2+-ATPase activity of the SR was reduced simultaneously with the degradation of the major ATPase protein in ischemia for 20 to 30 minutes. In the stunned myocardium, with occlusion of the LAD for 15 minutes and reperfusion, long-term reduction in the activity of the SR was noted simultaneously with a reduction in the percent of segment shortening, but without degradation of the ATPase protein of the SR. In the preconditioned myocardium, in which the LAD was occluded four times for five minutes each prior to LAD occlusion for 60 minutes and reperfusion, both ATPase activity and the SR ATPase protein were preserved In reperfusion of the LAD after occlusion for 10 to 30 minutes, reduction in Ca2+-ATPase activity and degradation of the ATPase protein occurred earlier, simultaneously with generation of free radicals, suggesting reperfusion injury. We conclude that pathophysiologic behaviors of the postischemic myocardium proceed in quite different ways depending upon the length of ischemia and will only be fully understood in the light of studies on ischemia and reperfusion of the heart muscle.