Wang P, Ba Z F, Chaudry I H
Department of Surgery, Michigan State University, East Lansing 48824-1315.
Surgery. 1994 Aug;116(2):169-75; discussion 175-6. doi: 10.1016/0300-9572(95)91008-b.
Although heparinization before hemorrhagic shock improves tissue perfusion and organ function, the anticoagulant properties of conventional heparin preclude its clinical use. The purpose of this study was to determine whether chemically modified heparin (CMH), which does not have any significant anticoagulant activity, produces any beneficial effects on hepatocellular and cardiovascular function and microcirculation after trauma-hemorrhage and resuscitation.
After induction of tissue trauma (that is, laparotomy), rats were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximum bleedout volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with three times the volume of shed blood with RL over 45 minutes, followed by two times RL and CMH (7 mg/kg body wt; approximately 10% of the anticoagulant activity of conventional heparin), conventional heparin (7 mg/kg), or normal saline solution over 60 minutes. Hepatocellular function, cardiac output, and microvascular blood flow were determined thereafter.
The results indicate that hepatocellular function, cardiac output, and microvascular blood flow in the liver, kidney, spleen, and small intestine decreased markedly after trauma-hemorrhage and resuscitation. Infusion of CMH or conventional heparin during resuscitation, however, restored or significantly improved the mentioned parameters.
Because CMH does not have any significant anticoagulant properties and because it restores or significantly improves hepatocellular function, cardiac output, and tissue perfusion, this agent appears to be a useful adjunct in the treatment of trauma and hemorrhagic shock, even in the absence of blood resuscitation.
尽管出血性休克前进行肝素化可改善组织灌注和器官功能，但传统肝素的抗凝特性使其无法用于临床。本研究的目的是确定化学修饰肝素（CMH），即无显著抗凝活性的肝素，在创伤性出血和复苏后对肝细胞、心血管功能及微循环是否具有任何有益作用。
诱导组织创伤（即剖腹术）后，将大鼠放血至平均动脉压为40 mmHg并维持该水平，直至以乳酸林格液（RL）形式回输40%的最大放血量。然后在45分钟内用3倍失血量的RL对动物进行复苏，随后在60分钟内用2倍RL以及CMH（7 mg/kg体重；约为传统肝素抗凝活性的10%）、传统肝素（7 mg/kg）或生理盐水进行复苏。此后测定肝细胞功能、心输出量及微血管血流量。
结果表明，创伤性出血和复苏后，肝细胞功能、心输出量以及肝、肾、脾和小肠的微血管血流量均显著下降。然而，复苏期间输注CMH或传统肝素可恢复或显著改善上述参数。
由于CMH无显著抗凝特性，且能恢复或显著改善肝细胞功能、心输出量及组织灌注，因此即使在未进行血液复苏的情况下，该药似乎也是治疗创伤和出血性休克的有用辅助药物。
