TITLE: PYRUVATE IMPROVES THE CORTICAL REDOX AND PHOSPHORYLATION POTENTIAL DURING HEMORRHAGIC SHOCK IN SWINE

AUTHORS: John Capacchione, MD, J Fontana, MD, Paul Mongan, MD
AFFILIATION: Uniformed Services University of the Health Sciences, Bethesda, MD.

INTRODUCTION: Severe hemorrhagic hypotension causes decreased cerebral blood flow and cerebral dysfunction. We evaluated if metabolic intervention with pyruvate could ameliorate these deleterious effects of hemorrhagic shock.
METHODS: 10 swine (32-37kg) anesthetized with halothane (0.8% ET) underwent rapid isobaric controlled arterial hemor- rhage (mean arterial pressure, MAP, 40mmHg). The MAP was maintained at 40mmHg for 4 hours. 30 minutes after hemorrhage, swine were given pyruvate (PYR, n=5) to attain blood levels of 5mM or osmotically matched hypertonic saline (HTS, n=5). Before and during hemorrhagic shock, cerebral cortical func- tional and metabolic status was monitored with cortical micro- dialysis and an electroencephalogram (EEG). In addition, freeze clamp cerebral cortical biopsies were performed before and at 1, 2 and 4 hours after the start of hemorrhage. Microdialysate was analyzed for glutamate (CMA 600). Biopsies were analyzed for lactate (L), pyruvate (P), ATP, phospho-creatine (PCr) and creatine (Cr) enzymatically by spectro-photometer. Changes in the EEG were scored by a blinded evaluator.
RESULTS: MAP was maintained at 40 mmHg during shock. While groups had similar hemorrhage volumes (1406 vs. 1415ml) and changes in serum osmolality, PYR extended the time until hemorrhage volume reinfusion to maintain the MAP at 40 mmHg (97 vs. 78 min p<0.05). Basal biopsy levels of ATP, PCr and Cr were similar in all animals. PYR improved the cortical redox (L/P ratio) and phosphorylation potential (ATP*PCr/Cr) during hemorrhage (FIG). PYR also delayed the time and peak levels of glutamate release (p<0.05) and showed less attenuation of EEG scores.
DISCUSSION: PYR 30 minutes after the start of hemorrhagic shock (MAP 40mmHg) delayed vascular decompensation. Despite equivalent perfusion pressures, PYR also improved the cerebral metabolic (redox and phosphorylation potential, glutamate release) and functional status.