Cunha-Goncalves Doris, Perez-de-Sa Valeria, Dahm Peter, Grins Edgars, Thörne Johan, Blomquist Sten
Faculty of Medicine, Department of Clinical Sciences, University of Lund, Lund, Sweden.
Shock. 2007 Jul;28(1):71-7. doi: 10.1097/shk.0b013e31804d18f6.
Sepsis-associated myocardial depression is associated with calcium desensitization and adrenergic uncoupling. We conducted a prospective randomized investigation on the effects of the calcium sensitizer, levosimendan, on hemodynamics, myocardial blood flow, and myocardial lactate metabolism during porcine endotoxemia. Twelve pigs were studied. Oxygen consumption was measured by indirect calorimetry, and myocardial blood flow was measured by retrograde thermodilution. Pulmonary, arterial, and venous indwelling catheters allowed measurements of cardiac output, vascular pressures, and blood sampling. Fluids were given at an average of 15 mL . kg . h. After baseline measurements (0 min), an infusion of Escherichia coli LPS (2 microg . kg . min) was started in all animals. Beginning at 100 min, six animals received levosimendan (50 microg . kg . h), whereas six control animals received placebo. The study lasted for 300 min. All animals responded to endotoxin with pulmonary hypertension, a transient decrease in cardiac output, tachycardia, and systemic hypotension. Levosimendan infusion decreased systemic vascular resistance (P = 0.001), coronary vascular resistance (P = 0.004), and mean arterial (P < 0.001) and coronary perfusion pressures (P < 0.001), whereas pulmonary hypertension was unaffected. Heart rate progressively increased in both groups and was significantly higher in the levosimendan group (P = 0.048). Myocardial blood flow remained unchanged in both groups; however, 80 min after the start of levosimendan infusion, left ventricular myocardial hypoxia ensued, as evidenced by a negative myocardial lactate gradient (P = 0.01). Two control and five levosimendan animals died before the end of the study. Early administration of levosimendan during porcine endotoxemia increased heart rate, caused arterial vasodilation, and decreased coronary perfusion pressure, resulting in myocardial hypoxia.
脓毒症相关的心肌抑制与钙脱敏和肾上腺素能解偶联有关。我们对钙增敏剂左西孟旦在猪内毒素血症期间对血流动力学、心肌血流量和心肌乳酸代谢的影响进行了一项前瞻性随机研究。研究了12头猪。通过间接量热法测量耗氧量，通过逆行热稀释法测量心肌血流量。肺动脉、动脉和静脉留置导管用于测量心输出量、血管压力和采血。平均每小时每千克体重给予15毫升液体。在基线测量（0分钟）后，所有动物开始输注大肠杆菌脂多糖（2微克·千克·分钟）。从100分钟开始，6只动物接受左西孟旦（50微克·千克·小时），而6只对照动物接受安慰剂。研究持续300分钟。所有动物对内毒素的反应均为肺动脉高压、心输出量短暂下降、心动过速和全身性低血压。输注左西孟旦可降低全身血管阻力（P = 0.001）、冠状动脉血管阻力（P = 0.004）以及平均动脉压（P < 0.001）和冠状动脉灌注压（P < 0.001），而肺动脉高压未受影响。两组心率均逐渐增加，且左西孟旦组显著更高（P = 0.048）。两组心肌血流量均保持不变；然而，在输注左西孟旦开始80分钟后，出现左心室心肌缺氧，心肌乳酸梯度为负即证明了这一点（P = 0.01）。2只对照动物和5只左西孟旦组动物在研究结束前死亡。在猪内毒素血症期间早期给予左西孟旦会增加心率、导致动脉血管舒张并降低冠状动脉灌注压，从而导致心肌缺氧。
