Horton J W, White J, Maass D, Sanders B
Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9160, USA.
J Appl Physiol (1985). 1998 Feb;84(2):695-702. doi: 10.1152/jappl.1998.84.2.695.
This study examined the effects of arginine supplement of fluid resuscitation from burn injury on cardiac contractile performance and bacterial translocation after a third-degree burn comprising 43% of the total body surface area in adult rats. Before burn injury, rats were instrumented to measure blood pressure; after burn (or sham injury), paired groups of sham-burned and burned rats were given vehicle (saline), L-arginine, D-arginine, or N-methyl-L-arginine (300 mg/kg in 0.3 ml of saline 30 min, 6 h, and 23 h postburn) plus fluid resuscitation; sham-burned rats received drug only. Twenty-four hours after burn trauma, hemodynamics were measured; the animals were then killed and randomly assigned to Langendorff heart studies or to studies examining translocation of gut bacteria. Burn rats treated with vehicle, D-arginine, or N-methyl-L-arginine had well-defined cardiocirculatory responses that included hypotension, tachycardia, respiratory compensation for metabolic acidosis, hypocalcemia, cardiac contractile depression, and significant bacterial translocation. Compared with values measured in vehicle-treated burn rats, L-arginine given after burn improved blood pressure, prevented tachycardia, reduced serum lactate levels, improved cardiac performance, and significantly reduced bacteria translocation, confirming that L-arginine administration after burn injury provided significant cardiac and gastrointestinal protection. Circulating neutrophil counts fell after burn trauma and serum glucagon levels rose, but these changes were not altered by pharmacological intervention. Our finding of significantly higher coronary perfusate guanosine 3',5'-cyclic monophosphate concentration in L-arginine-treated burn rats suggests that the beneficial effects of L-arginine were mediated by nitric oxide production.
本研究检测了烧伤后补充精氨酸进行液体复苏对成年大鼠心脏收缩功能及细菌移位的影响,这些大鼠的Ⅲ度烧伤面积达体表面积的43%。在烧伤前,对大鼠进行仪器植入以测量血压;烧伤(或假手术损伤)后,将配对的假烧伤和烧伤大鼠分为几组,分别给予赋形剂(生理盐水)、L-精氨酸、D-精氨酸或N-甲基-L-精氨酸(烧伤后30分钟、6小时和23小时,以0.3 ml生理盐水给予300 mg/kg)并进行液体复苏;假烧伤大鼠仅接受药物治疗。烧伤创伤24小时后,测量血流动力学;然后处死动物,随机分配用于Langendorff心脏研究或检测肠道细菌移位的研究。用赋形剂、D-精氨酸或N-甲基-L-精氨酸治疗的烧伤大鼠具有明确的心脏循环反应,包括低血压、心动过速、对代谢性酸中毒的呼吸代偿、低钙血症、心脏收缩功能抑制和显著的细菌移位。与赋形剂治疗的烧伤大鼠所测值相比,烧伤后给予L-精氨酸可改善血压、预防心动过速、降低血清乳酸水平、改善心脏功能并显著减少细菌移位,证实烧伤后给予L-精氨酸可提供显著的心脏和胃肠道保护。烧伤创伤后循环中性粒细胞计数下降,血清胰高血糖素水平升高,但这些变化未因药物干预而改变。我们发现L-精氨酸治疗的烧伤大鼠冠状动脉灌注液中3',5'-环磷酸鸟苷浓度显著更高,这表明L-精氨酸的有益作用是由一氧化氮生成介导的。