Pyruvate‐fortified Fluid Resuscitation Suppresses Inflammation and Arrhythmogenesis During Hemorrhagic Shock and Hindlimb Ischemia

Fluid resuscitation for hemorrhagic shock can elicit inflammatory and metabolic stress. We tested whether resuscitation with pyruvate can mitigate these effects. Goats (~25kg) were hemorrhaged to mean arterial pressure (MAP) of 50 mmHg, subjected to hindlimb ischemia with a tourniquet, and then resuscitated (10 ml/min iv) with lactate‐ (LR; n=4) or pyruvate‐ (PR; n=6) enriched Ringers solution for 90 min; tourniquet was released at 60 min. Time controls (TC, n=5) experienced neither hemorrhage nor hindlimb ischemia. At 4 h recovery, left ventricular myocardium (LV) and ischemic gastrocnemius (IG) were biopsied to measure myeloperoxidase (MPO), a marker of neutrophil infiltration. Peak plasma pyruvate concentrations (mM) were 3.03±0.83 in PR, 0.46±0.15 in LR (p<0.05 vs. PR) and 0.15±0.002 in TC. Systemic lactate/pyruvate redox state was higher in LR (30.3±4.5) vs PR (1.9±0.3; p<0.001) and TC (3.7±0.1; p<0.01). Although MAP fell post‐resuscitation in all groups, pulse pressure, a measure of systemic vasodilation, increased only 15% following PR vs 133% post‐LR and 59% in TC. PR lowered MPO activity by 30% in LV and 23% in IG vs LR. Pro‐arrhythmic QTc dispersion was 25±6 ms post‐LR vs. 7.7±0.9 ms post‐PR (p<0.05). Resuscitation with pyruvate stabilized peripheral resistance and electrocardiographic function and suppressed tissue inflammation ‐ all goals for fluid resuscitation. US Dept Defense W911NF0910086.