Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia.
OBJECTIVE
To test the hypothesis that fluid resuscitation with Ringer's solution enriched with pyruvate (PR), a physiological antioxidant and energy substrate, affords protection of myocardial metabolism and electrophysiological performance superior to lactated Ringer's (LR) during hypovolemia and hindlimb ischemia-reperfusion.


METHODS
Male domestic goats (25-30 kg) were exsanguinated to a mean arterial pressure of 48 ± 1 mmHg. Right hindlimb ischemia was imposed for 90 min by applying a tourniquet and femoral crossclamp. LR or PR, infused iv, delivered 0.05 mmol/kg per minute L-lactate or pyruvate, respectively, from 30 min hindlimb ischemia until 30 min post-ischemia. Time controls (TC) underwent neither hemorrhage, hindlimb ischemia nor resuscitation. Goats were sacrificed and left ventricular myocardium biopsied at 90 min fluid resuscitation (n = 6 per group) or 3.5 h later (n = 9 LR, 10 PR, 8 TC).


RESULTS
Myocardial 8-isoprostane content, phosphocreatine phosphorylation potential, creatine kinase activity, and heart rate-adjusted QT interval (QTc) variability were evaluated at 90 min resuscitation and 3.5 h post-resuscitation. PR sharply lowered pro-arrhythmic QTc variability vs LR (P < 0.05); this effect persisted 3.5 h post-resuscitation. PR lowered myocardial 8-isoprostane content, a product of oxidative stress, by 39 and 37% during and 3.5 h after resuscitation, respectively, vs LR. Creatine kinase activity fell 42% post-LR vs TC (P < 0.05), but was stable post-PR (P < 0.02 vs post-LR). PR doubled phosphocreatine phosphorylation potential, a measure of ATP free energy state, vs TC and LR (P < 0.05); this energetic enhancement persisted 3.5 h post-resuscitation.


CONCLUSIONS
By augmenting myocardial energy state and protecting creatine kinase activity, pyruvate-enriched resuscitation stabilized cardiac electrical function during central hypovolemia and hindlimb ischemia-reperfusion.
Hunaid A Gurji, Daniel W White, Jie Sun, Albert H Olivencia-Yurvati, Robert T Mallet, Departments of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
Hunaid A
HA
Gurji
Hunaid A Gurji, Daniel W White, Jie Sun, Albert H Olivencia-Yurvati, Robert T Mallet, Departments of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
Daniel W
DW
White
Hunaid A Gurji, Daniel W White, Jie Sun, Albert H Olivencia-Yurvati, Robert T Mallet, Departments of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
Besim
B
Hoxha
Hunaid A Gurji, Daniel W White, Jie Sun, Albert H Olivencia-Yurvati, Robert T Mallet, Departments of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
Jie
J
Sun
Hunaid A Gurji, Daniel W White, Jie Sun, Albert H Olivencia-Yurvati, Robert T Mallet, Departments of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
Albert H
AH
Olivencia-Yurvati
Hunaid A Gurji, Daniel W White, Jie Sun, Albert H Olivencia-Yurvati, Robert T Mallet, Departments of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107, United States.
Robert T
RT
Mallet
8-Isoprostane; Creatine kinase; Electrocardiogram; Hypovolemia; Phosphocreatine; Reactive oxygen species; Ringer’s lactate