Activation of pyruvate dehydrogenase improves heart function and metabolism after hemorrhagic shock

Jeffrey A. Kline, Peggy C. Maiorano, J. David Schroeder, Robert M. Grattan, Thomas C. Vary, John A. Watts

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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 = HR x PSP) was 23,000 ± 2733 with no DCA treatment v 362,769 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.O μmol/g weight -DCA, v 15.1 ± 0.9 and 14.7 ± 1.0 μmol/g dry weight +DCA, P < 0.05, both measurements). DCA administration also significantly reduced myocardial lactate contents (14.6 ± 2.7 μmol/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 μmol/g dry weight/min -DCA v 29.7 ± 2.0 μmol/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.

Original languageEnglish (US)
Pages (from-to)2465-2474
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume29
Issue number9
DOIs
StatePublished - Sep 1997
Externally publishedYes

Keywords

  • DCA
  • Dichloroacetate
  • Energy metabolism
  • Hemorrhage
  • Hemorrhagic shock
  • Lactic acid
  • PDH
  • Pyruvate dehydrogenase
  • Resuscitation
  • Shock

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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