Cardiovascular effects of levosimendan in the early stages of endotoxemia

被引:20
作者
Cunha-Goncalves, Doris [1 ]
Perez-de-Sa, Valeria [1 ]
Dahm, Peter [1 ]
Grins, Edgars [1 ]
Thoerne, Johan [1 ]
Blomquist, Sten [1 ]
机构
[1] Lund Univ, Dept Clin Sci, Fac Med, S-22100 Lund, Sweden
来源
SHOCK | 2007年 / 28卷 / 01期
关键词
coronary circulation; cardiotonic agents; lactates; myocardial oxygen consumption; sepsis; swine;
D O I
10.1097/shk.0b013e31804d18f6
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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(-1) . h(-1). After baseline measurements (0 min), an infusion of Escherichia coli LPS (2 mu g . kg(-1) . min(-1)) was started in all animals. Beginning at 100 min, six animals received levosimendan (50 mu g . kg(-1) . h(-1)), 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.
引用
收藏
页码:71 / 77
页数:7
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