Endothelial cell dysfunction occurs after hemorrhage in nonheparinized but not in preheparinized models.
Although hemorrhage produces alterations in hemodynamics and cellular functions, it is not known whether endothelial cell function is depressed under such conditions and, if so, whether preheparinization has any protective effect on this function. To study this, rats (with or without heparinization prior to hemorrhage, 1 U/g body wt) were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximal bleedout volume was returned in the form of lactated Ringer's solution (LR). The rats were then resuscitated with four times the volume of maximal bleedout in the form of LR. At 1.5 hr postresuscitation, the thoracic aorta was removed, cut into approximately 2.5-mm rings, and placed in organ chambers. Norepinephrine (2 x 10(-7) M) was applied to achieve near-maximal contraction, and dose responses for an endothelium-dependent vasodilator, acetylcholine, were determined. Hypoxia-induced contraction (an endothelium-dependent process) was also carried out using 95% N2:5% CO2. The results indicate that endothelium-dependent relaxation and contraction were markedly depressed following hemorrhage and resuscitation in nonheparinized, but not in preheparinized models. However, there was no significant difference in the relaxation induced by an endothelium-independent vasodilator, nitroglycerin, irrespective of heparinization. Thus, endothelial cell dysfunction (i.e., the depressed capacity of aortic endothelium to maximally release endothelium-derived relaxing and contracting factors) occurs after hemorrhage in nonheparinized, but not in preheparinized animals. Since trauma victims are not heparinized before the injury and since preheparinization protects endothelial cell function, pharmacologic agents to restore the depressed cellular function should be tested only in nonheparinized models of hemorrhage and resuscitation.
Wang
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Department of Surgery, Michigan State University, East Lansing 48824.
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Chaudry
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006493:Heparin / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D006493:Heparin; D005996:Nitroglycerin; D000109:Acetylcholine