Pyruvate improves cardiac electromechanical and metabolic recovery from cardiopulmonary arrest and resuscitation

Arti B. Sharma, E. Marty Knott, Jian Bi, Rodolfo R. Martinez, Jie Sun, Robert T. Mallet

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Abstract

Severe depletion of myocardial energy and antioxidant resources during cardiac arrest culminates in electromechanical dysfunction following recovery of spontaneous circulation (ROSC). A metabolic fuel and natural antioxidant, pyruvate augments myocardial energy and antioxidant redox states in parallel with its enhancement of contractile performance of stunned and oxidant-challenged hearts. This study tested whether pyruvate improves post-arrest cardiac function and metabolism. Beagles were subjected to 5 min cardiac arrest and 5 min open-chest cardiac compression (OCCC: 80 compressions min-1; aortic pressure 60-70 mmHg), then epicardial dc countershocks (5-10 J) were applied to restore sinus rhythm. Pyruvate was infused i.v. throughout OCCC and the first 25 min ROSC to a steady-state arterial concentration of 3.6 ± 0.2 mM. Control experiments received NaCl infusions. Phosphocreatine phosphorylation potential (∼PCr) and glutathione/glutathione disulfide ratio (GSH/GSSG), measured in snap-frozen left ventricle, indexed energy and antioxidant redox states, respectively. In control experiments, left ventricular pressure development, dP/dt and carotid flow initially recovered upon defibrillation, but then fell 40-50% by 3 h ROSC. ST segment displacement in lead II ECG persisted throughout ROSC. ∼PCr collapsed and GSH/GSSG fell 61% during arrest. Both variables recovered partially during OCCC and completely during ROSC. Pyruvate temporarily increased ∼PCr and GSH/GSSG during OCCC and the first 25 min ROSC and enhanced pressure development, dP/dt and carotid flow at 15-25 min ROSC. Contractile function stabilized and ECG normalized at 2-3 h ROSC, despite post-infusion pyruvate clearance and waning of its metabolic benefits. In conclusion, intravenous pyruvate therapy increases energy reserves and antioxidant defenses of resuscitated myocardium. These temporary metabolic improvements support post-arrest recovery of cardiac electromechanical performance.

Original languageEnglish
Pages (from-to)71-81
Number of pages11
JournalResuscitation
Volume66
Issue number1
DOIs
Publication statusPublished - 1 Jul 2005

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Keywords

  • Cardiac arrest
  • Electrocardiography
  • Free radical
  • Metabolism
  • Myocardial
  • Open-chest cardiac compression (OCCC)
  • Stunning

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