Rumsey W L, Kilpatrick L, Wilson D F, Erecinska M
Department of Biochemistry, University of Pennsylvania School of Medicine, Philadelphia 19104.
Am J Physiol. 1988 Dec;255(6 Pt 2):H1295-304. doi: 10.1152/ajpheart.1988.255.6.H1295.
The effects of sublethal endotoxemia on the regulation of coronary flow by myocardial metabolism were examined in the isolated perfused heart preparation. Fasted Sprague-Dawley rats were injected (ip) with either endotoxin (0.5 mg/kg of body wt) or 5% dextrose 12 h before heart perfusion. The efficacy of endotoxin treatment was determined by measurement of plasma [NH3] and [urea] and colonic temperature. During perfusion with buffer containing glucose-pyruvate, oxygen consumption and coronary flow were increased by 17 and 42%, respectively, in hearts from endotoxin-treated rats as compared with those from controls. In the hearts from endotoxemic animals, the mitochondrial [NAD+]/[NADH] was decreased by approximately 25%, and the active form of pyruvate dehydrogenase was increased by 36% as compared with control hearts. [ATP]f/[ADP]f[Pi] was unaltered. The enhanced metabolic rate was associated with comparable changes in peak systolic pressure development, maximal positive and negative dP/dt, and the tension-time index when measured in the isovolumetric preparation. In these hearts, stimulation of respiration by perfusion with an alternate source of fuel or inhibition by infusion of amytal elicited large, transient increases in the level of coronary flow that returned rapidly to prestimulus values. By contrast, in hearts from controls, the transient increase in flow was coupled to sustained vasodilation, i.e., approximately 30% rise in flow for either metabolic condition. In both groups, [ATP]f/[ADP]f[Pi] either increased or decreased with stimulation or inhibition of respiration, respectively. Adenosine (1.2 microM) produced a 35% increase in flow in the hearts from the control animals, whereas it was without significant effect in those from the endotoxin-treated animals. It is concluded that sublethal endotoxemia causes 1) an increased metabolic rate and enhanced mechanical activity in the heart and 2) an uncoupling of flow from regulation by cardiac metabolism.
在离体灌注心脏标本中研究了亚致死性内毒素血症对心肌代谢调节冠脉血流的影响。在心脏灌注前12小时，给禁食的斯普拉格-道利大鼠腹腔注射内毒素（0.5mg/kg体重）或5%葡萄糖。通过测定血浆[NH₃]、[尿素]和结肠温度来确定内毒素处理的效果。在用含葡萄糖-丙酮酸的缓冲液灌注期间，与对照组相比，内毒素处理大鼠心脏的耗氧量和冠脉血流量分别增加了17%和42%。在内毒素血症动物的心脏中，线粒体[NAD⁺]/[NADH]降低了约25%，与对照心脏相比，丙酮酸脱氢酶的活性形式增加了36%。[ATP]f/[ADP]f[Pi]未改变。在等容标本中测量时，代谢率的提高与收缩压峰值、最大正负dP/dt以及张力-时间指数的类似变化相关。在这些心脏中，用替代燃料源灌注刺激呼吸或用戊巴比妥钠输注抑制呼吸会引起冠脉血流水平的大幅短暂增加，并迅速恢复到刺激前的值。相比之下，在对照组心脏中，血流的短暂增加与持续的血管舒张相关，即在任何一种代谢条件下血流增加约30%。在两组中，[ATP]f/[ADP]f[Pi]分别随着呼吸的刺激或抑制而增加或降低。腺苷（1.2μM）使对照动物心脏的血流增加35%，而对内毒素处理动物的心脏无显著影响。结论是亚致死性内毒素血症导致：1）心脏代谢率增加和机械活动增强；2）血流与心脏代谢调节解偶联。
