TY - JOUR
T1 - Pyruvate stabilizes electrocardiographic and hemodynamic function in pigs recovering from cardiac arrest
AU - Cherry, Brandon H.
AU - Nguyen, Anh Q.
AU - Hollrah, Roger A.
AU - Williams, Arthur G.
AU - Hoxha, Besim
AU - Olivencia-Yurvati, Albert H.
AU - Mallet, Robert T.
N1 - Funding Information:
This work was supported by research grants R01 NS076975 from the U.S. National Institute of Neurological Disorders and Stroke and P01 AG022550 from the U.S. National Institute on Aging. BHC was supported by a predoctoral fellowship from the National Institute of Aging, Training in the Neurobiology of Aging, grant T31 AG020494. This work was conducted in partial fulfillment of the requirements for the PhD degree for BHC.
Publisher Copyright:
© 2015, © 2015 by the Society for Experimental Biology and Medicine.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - acidemia
KW - bicarbonate
KW - cardiopulmonary resuscitation
KW - phenylephrine
KW - pulseless electrical activity
KW - ventricular fibrillation
UR - http://www.scopus.com/inward/record.url?scp=84958281074&partnerID=8YFLogxK
U2 - 10.1177/1535370215590821
DO - 10.1177/1535370215590821
M3 - Article
C2 - 26088865
AN - SCOPUS:84958281074
SN - 1535-3702
VL - 240
SP - 1774
EP - 1784
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 12
ER -