This study was designed to test the hypothesis that activation of myocardial pyruvate dehydrogenase (PDH) would improve recovery of heart function after brief, severe hemorrhagic shock. Pentobarbital-anesthetized rats were instrumented to monitor arterial blood pressure and right ventricular pressures. Rats were hemorrhaged via femoral artery to 25-30 mmHg mean arterial pressure (MAP) for 60 min, followed by retransfusion of shed blood with either 1.0 cc saline with no dichloroacetate (-DCA) or 1.0 cc saline containing 150 mg/kg sodium dichloroacetate (+DCA). Rats were observed for 3 h after retransfusion. Hearts were freeze-clamped in situ for analysis of adenosine triphosphate (ATP), creatine phosphate (CrP), lactate and pyruvate content as well as PDH activity (PDHa) and total PDH activity (PDHt). Three h after retransfusion, the rate pressure product (RPP=HRxPSP) was 23 000+/-2733 with no DCA treatment v 36 2769 mmHg/min with DCA treatment (P<0.05, ANOVA). Treatment with DCA also increased myocardial tissue content of high energy phosphates (ATP=10.1+/-1.1 and CrP=5.8+/-1.0 micromol/g weight-DCA, v 15.1+/-0.9 and 14.7+/-1.0 micromol/g dry weight+DCA, P<0.05, both measurements). DCA administration also significantly reduced myocardial lactate contents (14.6+/-2.7 micromol/g dry weight-DCA v 5.9+/-1.0+DCA). Hemorrhagic shock did not change PDHa or PDHt compared to hearts obtained during the pre-hemorrhage period. Retransfusion with DCA significantly increased PDHa activity (6.8+/-1.1 micromol/g dry weight/min-DCA v 29.7+/-2.0 micromol/g dry weight/min+DCA). PDHt was not different between controls and DCA-treated groups. These data indicate that activation of myocardial PDH by adding DCA to retransfused blood improved heart function and metabolism after severe hemorrhagic shock.