The transport of metabolites between mitochondria and cytosol via the α-ketoglutarate-malate carrier serves to balance flux between the two spans of the tricarboxylic acid (TCA) cycle but is reduced in stunned myocardium. To examine the mechanism for reduced transporter activity, we followed the postischemic response of metabolite influx/efflux from mitochondria to stimulation of the malate-aspartate (MA) shuttle. Isolated rabbit hearts were either perfused with 2.5 mM [2-13C]acetate ( n = 7) or similarly reperfused ( n = 5) after 10-min ischemia. In other hearts, the MA shuttle was stimulated with a high cytosolic redox state (NADH) induced by 2.5 mM lactate in normal ( n = 6) or reperfused hearts ( n = 7). In normal hearts, the MA shuttle response accelerated transport from 8.3 ± 3.4 to 16.2 ± 5.0 μmol ⋅ min−1 ⋅ g dry wt−1. Although transport was reduced in stunned hearts, the MA shuttle was responsive to cytosolic NADH load, increasing transport from 3.4 ± 1.0 to 9.8 ± 3.7 μmol ⋅ min−1 ⋅ g dry wt−1. Therefore, metabolite exchange remains intact in stunned myocardium but responds to changes in TCA cycle flux regulation.
EFFECTS OF INESCAPABLE SHOCK UPON SUBSEQUENT FIXED RATIO-2 SHUTTLE RESPONSE
