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Custalow Catherine B.; Watts, John A.; Thornton, Lisa; O'Malley, Patrick; Barbee, Wayne R.; Grattan, Robert M.; Lopaschuk, Gary D.; Kline, Jeffrey A.
Shock: March 2001
Basic Science Investigations: PDF Only
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ABSTRACT—

This study tested the hypothesis that removal of fatty acids as a fuel source would improve cardiac efficiency at the expense of reduced cardiac contractile function in the isolated working heart after hemorrhageretransfusion. Non-heparinized male Sprague-Dawley rats were anesthetized with ketamine-xylazine and were hemorrhaged to a mean arterial blood pressure of 40 mmHg for 1 h. Two-thirds volume of shed blood was reinfused together with 0.9% NaCI in a volume equal to 2.3 times the shed blood volume, followed by continuous infusion of 0.9% NaCI at 10 mL/kg per h for 3 h. Hearts were removed and perfused in closed, recirculating working mode for 60 min to measure hydraulic work and cardiac efficiency. Rates of glycolysis and glucose oxidation were assessed with [5-3H/U-14C] glucose (11 mM) in the absence or presence of 0.4 mM palmitate. Compared to baseline measurements, hemorrhageretransfusion significantly reduced arterial blood glucose (228 ± 7 versus 118 ± 12 mg/dL) and non-esterified fatty acid concentrations (0.36 ± 0.01 versus 0.30 ± 0.02 mM), while elevating blood lactate (0.8 ± 0.1 versus 2.5 ± 0.4 mM). Perfusion of sham hearts with glucose-only did not alter cardiac work compared to shams perfused with glucose plus palmitate. However, shocked hearts perfused with glucose-only demonstrated a significant reduction in cardiac work compared to shocked hearts perfused with glucose plus palmitate and compared to sham hearts perfused with glucose only (P < 0.05, repeated measures ANOVA). Shocked hearts perfused with glucose plus palmitate showed no reduction in cardiac work compared to shams. Shocked hearts perfused with glucose-only had increased glucose oxidation rates compared to shams perfused with glucose plus palmitate. In sham hearts perfused with glucose-only, myocardial glycogen and triacylglycerol contents were significantly reduced compared to hearts freeze-clamped in situ. These endogenous fuels were not decreased in shocked hearts. These data indicate that hemorrhagic shock renders the heart unable to mobilize endogenous fuels, and suggest that withdrawal of fatty acid oxidation will impair myocardial energy metabolism during resuscitation.

*Department of Emergency Medicine, Division of Emergency Medicine Research, Carolinas Medical Center, Charlotte, North Carolina 28232; and †Department of Pharmacology and Pediatrics, University of Alberta, Edmunton, Canada

Received 17 Jul 2000, first review completed 18 Aug 2000; accepted in final form 30 Aug 2000

Address reprint requests to Jeffrey A. Kline, MD, Department of Emergency Medicine, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232-2861.

Supported by the Society of Academic Emergency Medicine Resident Research Award (C.B.C.) and the American Heart Association (J.A.K.).

©2001The Shock Society