Attenuation of burn-induced changes in hemodynamics and glucose metabolism by the PAF antagonist SRI 63-675

Charles Lang, Cornel Dobrescu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The importance of platelet-activating factor (PAF) in producing hypotension, hemoconcentration and alterations in carbohydrate metabolism following thermal injury was investigated in chronically catheterized rats. Animals were fasted overnight, anesthetized with pentobarbital, and then injected with saline or the PAF antagonist SRI 63-675 prior to a 25% body surface area scald injury. Burned animals showed a sustained 20-30 fall in mean arterial pressure that was attenuated by the PAF antagonist. Burn also produced a prolonged increased in hematocrit. Animals pretreated with SRI 63-675 showed a similar degree of polycythemia after 1 h, but thereafter hematocrit fell and was not different from sham-burned animals. Burn increased the plasma glucose (45-52%) and lactate (5-6 fold) concentrations, and tended to produce an early increase and a later decrease in the rate of glucose appearance (Ra). These metabolic changes were associated with elevated plasma levels of glucagon and catecholamines. The PAF antagonist prevented the hyperglycemia, reduced the hyperlactacidemia, and prevented the late fall of glucose Ra. Treated animals still showed increased levels of glucagon, while catecholamine concentrations were reduced by 50%. Short-term survival (4 h) was markedly improved (86 vs. 43%). These results suggest that PAF produced following thermal injury is responsible, at least in part, for the early hemodynamic changes and hemoconcentration. However, the role of PAF as a mediator of burn-induced glucose dyshomeostasis appears secondary to its hemodynamic effects.

Original languageEnglish (US)
Pages (from-to)207-214
Number of pages8
JournalEuropean Journal of Pharmacology
Volume156
Issue number2
DOIs
StatePublished - Nov 1 1988

All Science Journal Classification (ASJC) codes

  • Pharmacology

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