GLYCOLYSIS AND GLUCOSE-OXIDATION DURING REPERFUSION OF ISCHEMIC HEARTS FROM DIABETIC RATS

Stimulation of glucose oxidation by dichloroacetate (DCA) treatment is beneficial during recovery of ischemic hearts from non-diabetic rats. We therefore determined whether DCA treatment of diabetic rat hearts (in which glucose use is extremely low), increases recovery of functio n of hearts reperfused following ischemia. Isolated working hearts fro m 6 week streptozotocin-diabetic rats were perfused with 11 mM [2-H-3/ U-C-14]glucose, 1.2 mM palmitate, 20 mu U/ml insulin, and subjected to 30 min of no flow ischemia followed by 60 min reperfusion. Heart func tion (expressed as the product of heart rate and peak systolic pressur e), prior to ischemia, was depressed in diabetic hearts compared to co ntrols (HR x PSP x 10(-3) was 18.2 +/- 1 and 24.3 +/- 1 beats/mm Hg/mi n in diabetic and control hearts respectively) but recovered to pre-is chemic levels following ischemia, whereas recovery of control hearts w as significantly decreased (17.8 +/- 1 and 11.9 +/- 3 beats/mm Hg/min in diabetic and control hearts respectively). This enhanced recovery o f diabetic rat hearts occurred even though glucose oxidation during re perfusion was significantly reduced as compared to controls (39 +/- 6 and 208 +/- 42 nmol/min/g dry wt, in diabetic and control hearts respe ctively). Glycolytic rates ((H2O)-H-3 production) during reperfusion w ere similar in diabetic and control hearts (1623 +/- 359 and 2071 +/- 288 nmol/min/g dry wt, respectively). If DCA (1 mM) was added at reper fusion, hearts from control animals exhibited a significant improvemen t in function (HR x PSP x 10(-3) recovered to 20 +/- 4 beats/mm Hg/min ) that was accompanied by a 4-fold increase in glucose oxidation (from 208 +/- 42 to 753 +/- 111 nmol/min/g dry wt). DCA was without effect on functional recovery of diabetic rat hearts during reperfusion but d id significantly increase glucose oxidation from 39 +/- 6 to 179 +/- 4 4 nmol/min/g dry wt). These data suggest that, unlike control hearts, low glucose oxidation rates are not an important factor in reperfusion recovery of previously ischemic diabetic rat hearts.