Reperfusion induced enzyme release: washout effect or manifestation of reperfusion damage?

Abstract

Isolated isovolumically contracting rat hearts were subjected to ischaemia and subsequent reperfusion to determine whether reperfusion induced release of lactate dehydrogenase from the heart was due to washout of previously unperfused areas by reflow or a manifestation of myocardial damage occurring during reperfusion. Hearts were exposed to 2 h of ischaemia alone or to 2 h of ischaemia followed by reperfusion for at least 2 h. Below an ischaemic coronary flow rate of 40% of the preischaemic value drainage of enzymes liberated from irreversibly damaged myocytes was impaired owing to the presence of unperfused myocardium. The lactate dehydrogenase activity released during 2 h of ischaemia was maximally 60 U per heart and during 2 h of reperfusion maximally 251 U per heart (comprising together 89% of cardiac lactate dehydrogenase content). Lactate dehydrogenase activity released during reperfusion correlated with ischaemic coronary flow rate (r=−0.93). Reperfusion induced reflow of previously unperfused regions resulted in washout of liberated but trapped lactate dehydrogenase, predominantly responsible for lactate dehydrogenase release if ischaemia was severe (ischaemic flow rate below 40%). After the onset of reperfusion there was partial initial recovery of left ventricular developed pressure, with a gradual decline thereafter. In experiments in which ischaemia induced unperfused areas could be excluded — that is, at ischaemic flow rates of 40% or higher — reperfusion gave rise to lactate dehydrogenase release closely associated in time with die decline of left ventricular developed pressure. It is concluded that in this rat heart preparation reperfusion damage — namely, irreversible damage of myocardium occurring during reperfusion — takes place in previously underperfused (low flow) myocardium. The massive enzyme release observed immediately after the onset of reperfusion is a manifestation of ischaemia induced cell death occurring in myocardium that was completely deprived of perfusion during ischaemia (no flow).