Endothelial cell dysfunction occurs very early following trauma-hemorrhage and persists despite fluid resuscitation.
Although hemorrhage produces alterations in hemodynamics and cellular functions, it remains unknown if endothelial cell function is depressed in a nonheparinized model of trauma-hemorrhage and resuscitation. To study this, rats underwent a 5-cm midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleed-out volume was returned in the form of Ringer lactate (RL). They were then resuscitated with four times the volume of the shed blood with RL over 60 min. At the time of maximal bleed out (approximately 50 min from the onset of hemorrhage), 1.5, and 4 h after the completion of resuscitation, aortic rings (approximately 2.5 mm in length) were isolated and mounted in organ chambers. Dose responses for an endothelium-dependent vasodilator (acetylcholine) and endothelium-independent vasodilator (nitroglycerin) were determined. The results indicate that endothelium-dependent relaxation was depressed at the time of maximal bleed out and persisted even after resuscitation. However, there was no significant difference in nitroglycerin-induced relaxation at any point during the study period. In addition, hypoxia-induced contraction, a process mediated by endothelium-derived contracting factor, decreased significantly following hemorrhage and resuscitation. Thus endothelial cell dysfunction (i.e., reduced release of endothelium-derived relaxing and contracting factors) occurs very early after trauma-hemorrhage and persists despite fluid resuscitation.
Wang
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Department of Surgery, Michigan State University, East Lansing 48824.
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D006400:Hematocrit; D006470:Hemorrhage / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D000860:Hypoxia / Q000503:physiopathology; D007552:Isotonic Solutions / Q000627:therapeutic use; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D000077325:Ringer's Lactate; D014661:Vasoconstriction; D014664:Vasodilation; D014950:Wounds, Penetrating / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*
D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D005996:Nitroglycerin; D000109:Acetylcholine; D009638:Norepinephrine