Attenuation of burn-induced changes in hemodynamics and glucose metabolism by the PAF antagonist SRI 63-675.
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 increase 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.
Lang
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Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Dobrescu
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D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D001794:Blood Pressure / Q000187:drug effects; D002056:Burns / Q000097:blood* / Q000150:complications / Q000401:mortality; D002395:Catecholamines / Q000097:blood*; D005934:Glucagon / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000097:blood / Q000209:etiology; D007328:Insulin / Q000097:blood; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D010972:Platelet Activating Factor; D011804:Quinolines; C053130:SRI 63-675; D005934:Glucagon