Watkins J M, Spain D A, Krysztopik R J, Downard P J, Wilson M A, Garrison R N
Department of Surgery, University of Louisville School of Medicine, Kentucky 40292, USA.
J Surg Res. 1996 Dec;66(2):154-8. doi: 10.1006/jsre.1996.0388.
Multiple system organ failure (MOF) remains a major source of morbidity and mortality in trauma patients. Despite restoration of central hemodynamics, intestinal hypoperfusion can persist. Mucosal ischemia and barrier breakdown are factors in the genesis of MOF. Heparan sulfate is a gycosaminoglycan similar to heparin, but with minimal anticoagulant properties. As an adjunct to resuscitation, it improves immunologic function and restores mucosal oxygenation and function. We hypothesized that resuscitation with heparan following hemorrhage wound prevents intestinal hypoperfusion.
In vivo videomicroscopy was used to study small intestine microcirculation in rats. Animals were hemorrhaged to 50% of baseline mean arterial pressure (MAP) and maintained there. Resuscitation was initiated when the return of 10% shed blood was required to keep MAP at 50%. Animals received either heparan (7 mg/kg/1 ml saline) or saline (1 ml) followed by the remaining shed blood and an equal volume of saline. MAP, cardiac output (CO), A1 arteriole diameters, and flow were determined.
Resuscitation of the saline control group resulted in normal MAP with elevation of CO to 25-40% above baseline. The heparan group had return of MAP but only a moderate increase in CO (7-15%). Saline resuscitation led to progressive deterioration in A1 diameters and flow. The addition of heparan prevented delayed A1 constriction and significantly improved perfusion.
Heparan prior to resuscitation improved intestinal perfusion, despite a relative reduction in CO. Improvement in nutrient blood flow may protect the mucosal barrier, reducing the incidence of MOF, and suggests that heparan may be useful in resuscitation of trauma patients.
多系统器官功能衰竭（MOF）仍是创伤患者发病和死亡的主要原因。尽管中心血流动力学已恢复，但肠道灌注不足可能持续存在。黏膜缺血和屏障破坏是MOF发生的因素。硫酸乙酰肝素是一种类似于肝素的糖胺聚糖，但抗凝特性极小。作为复苏的辅助手段，它可改善免疫功能并恢复黏膜氧合和功能。我们假设出血性创伤后用硫酸乙酰肝素复苏可预防肠道灌注不足。
采用体内视频显微镜研究大鼠小肠微循环。将动物放血至基线平均动脉压（MAP）的50%并维持在该水平。当需要回输10%的失血以将MAP维持在50%时开始复苏。动物接受硫酸乙酰肝素（7mg/kg/1ml生理盐水）或生理盐水（1ml），随后回输剩余失血和等量生理盐水。测定MAP、心输出量（CO）、A1小动脉直径和血流量。
生理盐水对照组复苏后MAP正常，CO升高至基线以上25 - 40%。硫酸乙酰肝素组MAP恢复，但CO仅适度增加（7 - 15%）。生理盐水复苏导致A1直径和血流量逐渐恶化。添加硫酸乙酰肝素可防止A1延迟收缩并显著改善灌注。
尽管CO相对降低，但复苏前使用硫酸乙酰肝素可改善肠道灌注。营养血流的改善可能保护黏膜屏障，降低MOF的发生率，这表明硫酸乙酰肝素可能对创伤患者的复苏有用。
