Intermittent brief periods of ischemia have a cumulative effect and may cause myocardial necrosis.

Abstract

SUMMARY We investigated the effects of brief intermittent periods of ischemia on myocardial viability. Brief periodic coronary occlusions were produced up to 18 times by inflating and deflating the balloon of an intracoronary #2F catheter for periods of 15, 10 or 5 minutes, followed by 15-minute periods of reperfusion. Creatine kinase (CK) release, triphenyl tetrazolium chloride staining, and light and electron microscopy were used to detect the presence of myocardial necrosis. For the study of CK release, blood was taken from the great cardiac vein and the aorta before and at 5-minute intervals during each left anterior descending coronary occlusion, as well as during and 1, 5, 10 and 15 minutes after balloon deflation. In seven of 24 dogs with 15-minute occlusions, in five of 21 dogs with 10-minute occlusions, and in three of 32 dogs with 5-minute occlusions, small but distinct areas of subendocardial necrosis were present. In all dogs with morphologic proof of necrosis, there was periodic release of CK into the great cardiac vein, which peaked immediately after reperfusion, reflecting CK washout. Thus, brief periods of ischenia, which when single do not cause necrosis, have a cumulative effect and may cause myocardial necrosis. This mechanism of necrosis may be relevant clinically in patients with frequent anginal episodes. Since many dogs of this study did not have any myocardial necrosis, the findings also suggest that intermittent repefdusion has a beneficial effect and may prevent necrosis, even when total occlusion time exceeds 200 minutes.EXPERIMENTAL STUDIES have established that to cause myocardial necrosis, an ischemic injury must be of sufficient duration and severity. Even with the severest ischemia in dogs, the injury must be present for at least 20-30 minutes before necrosis will occur.1 For example, if flow is restored after 15 minutes of ischemia, no myocardial necrosis will be present. ' However, even when ischemia is brief and myocardial necrosis does not occur, there is usually a lengthy delay in return of normal function and metabolism in the injured myocardium.2-Therefore, we evaluated the possibility that brief periods of ischemia before the myocardium has fully recovered from the effects of preceding episodes of ischemia may gradually increase the degree of injury to the point of nonreversibility and necrosis. Methods PreparationThe study was with room air was instituted with a Harvard respirator. Systemic blood pressure was measured through a catheter inserted into the femoral artery. A #5F catheter was inserted through the external jugular vein under fluoroscopic control into the coronary sinus and advanced into the great cardiac vein. The position was verified by injection of contrast material. A #7F Judkins catheter was inserted through the left carotid artery into the ostium of the left anterior descending coronary artery (LAD). A #2F Fogarty catheter was then passed through the lumen of the Judkins catheter and advanced 2-3 cm into the LAD. The Judkins catheter was withdrawn into...

Molecular mechanism and therapy application of necrosis during myocardial injury

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Cardiac Effects of ST‐6, a Novel Cyclohexane Dicarboximide Derivative

“…Such vasodilating activity might contribute to the reduction in perfusion pressure of the reperfused heart, leading to the prevention of "no reflow" phenomenon. It is generally accepted that CK released from the heart during reperfusion is a marker for myocardial cell death (5,25). The CK activity of the perfusate was increased upon reperfusion.…”