title: Activation of pyruvate dehydrogenase improves heart function and metabolism after hemorrhagic shock.
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=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.
authors.affiliation: Research Division, Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC 28232, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Kline
authors.forename: P C
authors.initials: PC
authors.lastname: Maiorano
authors.forename: J D
authors.initials: JD
authors.lastname: Schroeder
authors.forename: R M
authors.initials: RM
authors.lastname: Grattan
authors.forename: T C
authors.initials: TC
authors.lastname: Vary
authors.forename: J A
authors.initials: JA
authors.lastname: Watts
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001158:Arteries; D001774:Blood Chemical Analysis; D001794:Blood Pressure; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004734:Energy Metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010710:Phosphates; D011768:Pyruvate Dehydrogenase Complex / Q000187:drug effects / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000378:metabolism*; D016276:Ventricular Function
chemical_list: D010710:Phosphates; D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D003999:Dichloroacetic Acid