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 min of severe ischemia in vivo, were studied. Changes in the adenine nucleotide pool, cell volume regulation, myocardial Ca and ultrastructure were studied at the end of 15 min of ischemia and after 0.5, 0.3 and 20 min of reflow. Before reperfusion, ATP and the adenylate pool decreased by 63% and 44% of control, respectively, and the adenylate charge was reduced to 0.65. After 3 min of reperfusion, the adenylate charge was restored to control by the rephosphorylation of adenosine mono- and diphosphate, but ATP was still reduced by 45%. Mild tissue edema was detected after 0.5 min of reflow and persisted throughout 20 min of reperfusion. Theincreased tissue H2O was accompanied by a slight increase in Na and a marked increase in tissue K. Although massive Ca accumulation develops when irreversibly injured tissue is reperfused, no Ca overload was detected during early reperfusion of reversibly injured myocytes. Reperfusion for 3 min exaggerated the mitochondrial swelling induced by 15 min of ischemia but after 20 min 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. Although adenine nucleotide repletion occurs very slowly, the adenylate charge was restored after 3 min, indicating rapid resumption of mitochondrial ATP production. Ca overload was not detected, but myocardial edema and increased K persisted throughout the 20 min of reperfusion. The ultrastructural consequences of ischemia were nearly reversed after 20 min of reperfusion.