title: Pyruvate stabilizes electrocardiographic and hemodynamic function in pigs recovering from cardiac arrest.
abstract: Cardiac electromechanical dysfunction may compromise recovery of patients who are initially resuscitated from cardiac arrest, and effective treatments remain elusive. Pyruvate, a natural intermediary metabolite, energy substrate, and antioxidant, has been found to protect the heart from ischemia-reperfusion injury. This study tested the hypothesis that pyruvate-enriched resuscitation restores hemodynamic, metabolic, and electrolyte homeostasis following cardiac arrest. Forty-two Yorkshire swine underwent pacing-induced ventricular fibrillation and, after 6 min pre-intervention arrest, 4 min precordial compressions followed by transthoracic countershocks. After defibrillation and recovery of spontaneous circulation, the pigs were monitored for another 4 h. Sodium pyruvate or NaCl were infused i.v. (0.1 mmol·kg(-1)·min(-1)) throughout precordial compressions and the first 60 min recovery. In 8 of the 24 NaCl-infused swine, the first countershock converted ventricular fibrillation to pulseless electrical activity unresponsive to subsequent countershocks, but only 1 of 18 pyruvate-treated swine developed pulseless electrical activity (relative risk 0.17; 95% confidence interval 0.13-0.22). Pyruvate treatment also lowered the dosage of vasoconstrictor phenylephrine required to maintain systemic arterial pressure at 15-60 min recovery, hastened clearance of excess glucose, elevated arterial bicarbonate, and raised arterial pH; these statistically significant effects persisted up to 3 h after sodium pyruvate infusion, while infusion-induced hypernatremia subsided. These results demonstrate that pyruvate-enriched resuscitation achieves electrocardiographic and hemodynamic stability in swine during the initial recovery from cardiac arrest. Such metabolically based treatment may offer an effective strategy to support cardiac electromechanical recovery immediately after cardiac arrest.
authors.affiliation: Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA Institute of Aging and Alzheimer's Disease Research, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA.
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Cherry
authors.affiliation: Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA.
authors.forename: Anh Q
authors.initials: AQ
authors.lastname: Nguyen
authors.affiliation: Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Hollrah
authors.affiliation: Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA.
authors.forename: Arthur G
authors.initials: AG
authors.lastname: Williams
authors.affiliation: Department of Emergency Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Besim
authors.initials: B
authors.lastname: Hoxha
authors.affiliation: Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA Department of Surgery, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA.
authors.forename: Albert H
authors.initials: AH
authors.lastname: Olivencia-Yurvati
authors.affiliation: Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA Department of Surgery, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA Robert.mallet@unthsc.edu.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Mallet
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D016887:Cardiopulmonary Resuscitation / Q000379:methods; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006323:Heart Arrest / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006943:Hyperglycemia / Q000209:etiology / Q000517:prevention & control; D006955:Hypernatremia / Q000209:etiology / Q000517:prevention & control; D007262:Infusions, Intravenous; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D019289:Pyruvic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D014662:Vasoconstrictor Agents; D019289:Pyruvic Acid
keywords: acidemia; bicarbonate; cardiopulmonary resuscitation; phenylephrine; pulseless electrical activity; ventricular fibrillation