Reperfusion after Cardiac Ischemia

Varadarajan, Srinivasan G., Jianzhong An, Enis Novalija, Steven C. Smart, and David F. Stowe. Changes in [Na]i, compartmental [Ca ], and NADH with dysfunction after global ischemia in intact hearts. Am J Physiol Heart Circ Physiol 280: H280–H293, 2001.—We measured the effects of global ischemia and reperfusion on intracellular Na, NADH, cytosolic and mitochondrial (subscript mito) Ca, relaxation, metabolism, contractility, and Ca sensitivity in the intact heart. Langendorff-prepared guinea pig hearts were crystalloid perfused, and the left ventricular (LV) pressure (LVP), first derivative of LVP (LV dP/dt), coronary flow, and O2 extraction and consumption were measured before, during, and after 30-min global ischemia and 60-min reperfusion. Ca, Na, and NADH were measured by luminescence spectrophotometry at the LV free wall using indo 1 and sodium benzofuran isophthalate, respectively, after subtracting changes in tissue autofluorescence (NADH). Mitochondrial Ca was assessed by quenching cytosolic indo 1 with MnCl2. Mechanical responses to changes in cytosolic-systolic (subscript sys), diastolic (subscript dia), and mitochondrial Ca were tested over a range of extracellular [Ca] before and after ischemia-reperfusion. Both [Ca]sys and [Ca ]dia doubled at 1-min reperfusion but returned to preischemia values within 10 min, whereas [Ca]mito was elevated over 60-min reperfusion. Reperfusion dissociated [Ca]dia and [Ca]sys from contractile function as LVPsys-dia and the rise in LV dP/dt (LV dP/dtmax) were depressed by one-third and the fall in LV dP/dt (LV dP/dtmin) was depressed by one-half at 30-min reperfusion, whereas LVPdia remained markedly elevated. [Ca]sys-dia sensitivity at 100% LV dP/dtmax was not altered after reperfusion, but [Ca]dia at 100% LV dP/ dtmin and [Ca ]mito at 100% LV dP/dtmax were markedly shifted right on reperfusion (ED50 136 and 1125 nM [Ca ], respectively) with no change in slope. NADH doubled during ischemia but returned to normal on initial reperfusion. The intracellular [Na] ([Na]i) increased minimally during ischemia but doubled on reperfusion and remained elevated at 60-min reperfusion. Thus Na and Ca temporally accumulate during initial reperfusion, and cytosolic Ca returns toward normal, whereas [Na]i and [Ca ]mito remain elevated on later reperfusion. Na loading likely contributes to Ca overload and contractile dysfunction during reperfusion. cardiac injury; contractility and relaxation; cytosolic Ca; mitochondrial Ca; myocardium; intracellular sodium concentration