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Pyruvate‐fortified Fluid Resuscitation Suppresses Inflammation and Arrhythmogenesis During Hemorrhagic Shock and Hindlimb Ischemia
Author(s) -
Gurji Hunaid,
Hoxha Besim,
Flaherty Devin,
Sun Jie,
Schulz Diana,
Blaylock Jessica,
OlivenciaYurvati Albert,
Mallet Robert
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.591.5
Subject(s) - resuscitation , medicine , tourniquet , myeloperoxidase , ischemia , shock (circulatory) , mean arterial pressure , anesthesia , hindlimb , blood pressure , endocrinology , inflammation , heart rate
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.