Pagel P S, McGough M F, Hettrick D A, Lowe D, Tessmer J P, Jamali I N, Warltier D C
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
J Cardiovasc Pharmacol. 1997 May;29(5):563-73. doi: 10.1097/00005344-199705000-00001.
We examined the left ventricular (LV) mechanical actions of levosimendan (LSM) before and after the development of pacing-induced cardiomyopathy in conscious dogs chronically instrumented for measurement of aortic and LV pressure, +dP/dt, subendocardial segment length, and cardiac output (CO). The slope (Mw) of the regional preload recruitable stroke work relation was used to assess myocardial contractility. Diastolic function was evaluated with a time constant of isovolumic relaxation (tau), the maximal rate of segment-lengthening velocity (dL/dt), and a regional chamber-stiffness constant (Kp). On different experimental days, dogs were assigned to receive LSM (12- or 24-microgram/kg loading dose and 0.2 or 0.4 microgram/kg/min infusion) before rapid ventricular pacing was initiated. Dogs were then paced at 240 beats/min for 22 +/- 2 days, and the low and high doses of LSM were repeated on separate days. LSM increased Mw and +dP/dt in dogs before the initiation of pacing, consistent with enhanced myocardial contractility. LSM also improved indices of LV diastolic function (decreases in tau and Kp and increases in dL/dt) in dogs before pacing. Rapid ventricular pacing over a 3-week period increased LV end-diastolic pressure and produced systolic (decreases in Mw and +dP/dt) and diastolic (increases in tau and Kp and decreases in dL/dt) dysfunction. LSM significantly (p < 0.05) increased Mw (54 +/- 3 to 98 +/- 6 mm Hg) +dP/dt and dL/dt (57 +/- 13 to 72 +/- 13 mm/s) and decreased tau (66 +/- 4 to 52 +/- 3 ms) and Kp (1.14 +/- 0.14 to 0.71 +/- 0.03 mm-1) in the presence of LV dysfunction. In contrast to the findings in normal dogs, however, LSM did not alter heart rate and calculated indices of myocardial oxygen consumption in dogs after pacing. The findings indicate that LSM produces favorable alterations in hemodynamics and positive inotropic and lusitropic effects in conscious dogs with left ventricular dysfunction.
我们在长期植入用于测量主动脉和左心室压力、+dP/dt、心内膜下节段长度和心输出量（CO）的清醒犬中，研究了起搏诱导性心肌病发生前后左西孟旦（LSM）对左心室（LV）的机械作用。用局部可募集的前负荷搏功关系的斜率（Mw）来评估心肌收缩力。用等容舒张时间常数（tau）、节段最大延长速度（dL/dt）和局部心室僵硬度常数（Kp）来评估舒张功能。在不同的实验日，在开始快速心室起搏前，将犬分为接受LSM（负荷剂量12或24微克/千克，输注速度0.2或0.4微克/千克/分钟）的组。然后将犬以240次/分钟的频率起搏22±2天，并在不同的日子重复给予低剂量和高剂量的LSM。在起搏开始前，LSM增加了犬的Mw和+dP/dt，这与心肌收缩力增强一致。LSM还改善了起搏前犬左心室舒张功能指标（tau和Kp降低，dL/dt增加）。为期3周的快速心室起搏增加了左心室舒张末期压力，并导致收缩功能障碍（Mw和+dP/dt降低）和舒张功能障碍（tau和Kp增加，dL/dt降低）。在存在左心室功能障碍的情况下，LSM显著（p<0.05）增加了Mw（从54±3至98±6毫米汞柱）、+dP/dt和dL/dt（从57±13至72±13毫米/秒），并降低了tau（从66±4至52±3毫秒）和Kp（从1.14±0.14至0.71±0.03毫米-1）。然而，与正常犬的结果不同，LSM在起搏后并未改变犬的心率和计算得出的心肌氧耗指标。这些结果表明，LSM在患有左心室功能障碍的清醒犬中产生了有利的血流动力学改变以及正性肌力和舒张期促松弛作用。
