Reversal of permeability transition during recovery of hearts from ischemia and its enhancement by pyruvate

We have used mitochondrial entrapment of 2-deoxy-D[H-3]glucose (2-DG) to de monstrate that recovery of Langendorff-perfused rat hearts from ischemia is accompanied by reversal of the mitochondrial permeability transition (MPT) . In hearts loaded with 2-DG before 40 min of ischemia and 25 min of reperf usion, 2-DG entrapment [expressed as 10(5) x (mitochondrial 2-[H-3]DG dpm p er unit citrate synthase)/ (total heart 2-[H-3]DG dpm/g wet wt)] increased from 11.1 +/- 1.3 (no ischemia, n = 4) to 32.5 +/- 1.9 (n = 6; P < 0.001). In other experiments, 2-DG was loaded after 25 min of reperfusion to determ ine whether some mitochondria that had undergone the MPT during the initial phase of reperfusion subsequently "resealed" and thus no longer took up 2- DG. The reduction of 2-DG entrapment to 20.6 +/- 2.4 units (n = 5) confirme d that this was the case. Pyruvate (10 mM) in the perfusion medium increase d recovery of left ventricular developed pressure from 57.2 +/- 10.3 to 98. 9 +/- 10.8% (n = 6; P < 0.05) and reduced entrapment of 2-DG loaded preisch emically and postischemically to 23.5 +/- 1.5 (n = 4; P < 0.001) and 10.5 /- 0.5 (n = 4; P < 0.01) units, respectively. The presence of pyruvate incr eased tissue lactate content at the end of ischemia and decreased the efflu ent pH during the initial phase of reperfusion concomitant with an increase in lactate output. We suggest that pyruvate may inhibit the MPT by decreas ing pH(i) and scavenging free radicals, thus protecting hearts from reperfu sion injury.