Effect of reperfusion late in the phase of reversible ischemic injury. Changes in cell volume, electrolytes, metabolites, and ultrastructure.

Abstract

The acute effects of reperfusion on myocardium reversibly damaged by 15 minutes of severe ischemia in vivo, were studied. Changes in the adenine nucleotide pool, cell volume regulation, myocardial calcium, and ultrastructure were studied at the end of 15 minutes of ischemia and after 0.5, 3.0, and 20 minutes of reflow. Before reperfusion, adenosine triphosphate and the adenylate pool decreased by 63% and 44% of control, respectively, and the adenylate charge was reduced to 0.65. After 3 minutes of reperfusion, the adenylate charge was restored to control by the rephosphorylation of adenosine mono- and diphosphate, but adenosine triphosphate was still reduced by 45%. Mild tissue edema was detected after 0.5 minute of reflow and persisted throughout 20 minutes of reperfusion. The increased tissue water was accompanied by a slight increase in sodium and a marked increase in tissue potassium. Although massive calcium accumulation develops when irreversibly injured tissue is reperfused, no calcium overload was detected during early reperfusion of reversibly injured myocytes. Reperfusion for 3 minutes exaggerated the mitochondrial swelling induced by 15 minutes of ischemia but after 20 minutes of reperfusion, myocardial ultrastructure was essentially normal except for rare swollen, or disrupted, mitochondria. Thus, the cellular abnormalities associated with brief periods of ischemia persist for variable periods of time after reperfusion of reversibly injured myocytes. First: although adenine nucleotide repletion occurs very slowly, the adenylate charge was restored after 3 minutes, indicating rapid resumption of mitochondrial adenosine triphosphate production. Second: calcium overload was not detected, but myocardial edema and increased potassium persisted throughout the 20 minutes of reperfusion. Third: the ultrastructural consequences of ischemia were nearly reversed after 20 minutes of reperfusion.

Myocardial reperfusion: a double-edged sword?

“…After 15 min of coronary occlusion, myocardial ATP concentration decreases substantially; it remains significantly depressed for many hours to days of reperfusion and usually returns to normal by 7 d (25,66,67). In other studies, creatine phosphate was shown also to fall markedly within minutes following coronary occlusion but to return to normal quite rapidly during coronary reperfusion.…”

“…While this increase is dramatic in irreversibly injured cells, it may also be seen transiently and to a lesser extent in reversibly injured tissue (24,25). This so-called "explosive" cell swelling of irreversibly injured cells (26) appears to be caused by an ischemia-induced sarcolemmal abnormality which causes a serious defect in regulation of cell volume and which is associated with marked increases in tissue water, sodium, chloride, and calcium.…”

Failure of the xanthine oxidase inhibitor allopurinol to limit infarct size after ischemia and reperfusion in dogs.

“…'°The xanthine oxidase reaction is of particular interest because large quantities of hypoxanthine, and its precursor inosine, accumulate rapidly in severely ischemic myocardium as a consequence of the degradation of the purine nucleotides."' 12 Especially when reperfusion is established, the xanthine oxidase reaction, fueled by an initially large substrate supply plus abundant oxygen resulting from reactive hyperemia, might produce an excessive load of superoxide anion. The latter might cause death of myocytes that would otherwise have survived the temporary period of ischemia.…”

Identification of myocardial reperfusion with echo planar magnetic resonance imaging. Discrimination between occlusive and reperfused infarctions.

“…Electromicroscopic study also indicates that the recovery of cellular ultrastructure in reversibly injured myocardium occurs soon after reperfusion. 35 Previous studies in patients4'5 with occlusive or reperfused myocardial infarctions using Ti enhancing agent indicated that they could not be consistently distinguished using the conventional spin echo MR imaging technique. This discrepancy with the present study may be due to the fact that the long acquisition time of spin-echo imaging results in images displaying the steady-state phase of contrast media distribution, which may be influenced considerably by collateral flow and diffusion of contrast media in the infarcted region, even in occlusive infarctions.…”