Pyruvate Stabilizes electrocardiographic and hemodynamic function in pigs recovering from cardiac arrest

Purpose: Cardiac electromechanical dysfunction may compromise recovery of patients who are initially resuscitated from cardiac arrest, and effective treatments for this post-arrest cardiac dysfunction 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. Methods: Yorkshire swine (30 ± 0.7 kg; 23 male, 19 female) underwent pacing-induced ventricular fibrillation and, after 6 min pre-intervention arrest, 4 min precordial compressions followed by transthoracic countershocks. After 4 min CPR, direct current countershocks were administered with external paddles to restore cardiac rhythm. Up to three 6-7 J/kg countershocks were applied, followed by up to three 8-12 J/kg countershocks, at 30 s intervals with intervening CPR, until spontaneous cardiac rhythm was restored. After defibrillation and recovery of spontaneous circulation, the pigs were monitored for another 4 h. Sodium pyruvate (n=11) or NaCl control (n=12) were infused iv (0.1 mmol-1 kg-1 min-1) throughout precordial compressions and the first 60 min recovery. Sham control pigs (n=7; 3 male, 4 female) were instrumented, anesthetized, and mechanically ventilated, but not subjected to cardiac arrest, CPR or defibrillation. The sham protocol was the same duration as the cardiac arrest-resuscitation protocol, and these pigs received intravenous NaCl infusion for a period corresponding to that of treatment infusions in the cardiac arrest experiments. Results: In 8 of the 24 NaCl-infused cardiac arrests, the first countershock converted ventricular fibrillation to pulseless electrical activity unresponsive to subsequent countershocks, but only 1 of 18 pyruvate-treated arrests 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, hastened clearance of excess glucose, elevated arterial bicarbonate, and raised arterial pH; these effects persisted up to 3h after pyruvate infusion. Conclusion: Pyruvate-enriched resuscitation fosters electrocardiographic and hemodynamic stability in swine recovering from cardiac arrest.