Goldman S, Olajos M, Morkin E
J Pharmacol Exp Ther. 1982 Jul;222(1):270-5.
The interaction of verapamil with three known positive inotropic stimuli, ouabain, dopamine and postextrasystolic potentiation (PESP), was studied in 10 conscious dogs. Implanted sonomicrometer crystals and solid state pressure transducers were used to evaluate left atrial (LA) and left ventricular (LV) function while heart rate was held constant by atrial pacing. Ouabain (0.025 mg/kg) and dopamine (3-5 micrograms/kg/min) were administered in amounts sufficient to increase LV dP/dt by about 20%. PESP was achieved by using a programmed stimulator to introduce atrial premature beats. Each of these inotropic interventions caused significant (P less than .05) increases in LV dp/dt, LV fractional shortening, LA fractional shortening LV-velocity of circumferential fiber shortening (Vcf) and LA-Vcf. Administration of a single i.v. dose of verapamil (0.03 mg/kg) caused no change in base-line mechanical and hemodynamic parameters. However, when verapamil was given during the increased inotropic state resulting from ouabain or dopamine administration, significant (P less than .05) decreases occurred in LV dP/dt, LV fractional shortening, LA fractional shortening, LV-Vcf and LA-VCf. Verapamil did not alter the positive inotropic response to PESP in the LV or LA. Thus, a dose of verapamil that did not change resting indices of myocardial contractility depressed function significantly during positive inotropic responses to ouabain and dopamine. This negative inotropic effect seemed to be selective because verapamil did not alter the response to PESP.
在10只清醒犬中研究了维拉帕米与三种已知的正性肌力刺激物（哇巴因、多巴胺和期前收缩后增强，PESP）之间的相互作用。植入的超声微测晶体和固态压力传感器用于评估左心房（LA）和左心室（LV）功能，同时通过心房起搏使心率保持恒定。给予哇巴因（0.025mg/kg）和多巴胺（3 - 5μg/kg/min），剂量足以使左心室dp/dt增加约20%。通过使用程控刺激器引入房性早搏来实现PESP。这些正性肌力干预措施中的每一种均使左心室dp/dt、左心室缩短分数、左心房缩短分数、左心室圆周纤维缩短速度（Vcf）和左心房Vcf显著（P<0.05）增加。静脉注射单剂量维拉帕米（0.03mg/kg）对基线机械和血流动力学参数无影响。然而，当在哇巴因或多巴胺给药导致的正性肌力增强状态期间给予维拉帕米时，左心室dp/dt、左心室缩短分数、左心房缩短分数、左心室Vcf和左心房Vcf显著（P<0.05）降低。维拉帕米并未改变左心室或左心房对PESP的正性肌力反应。因此，一剂不改变心肌收缩力静息指标的维拉帕米在对哇巴因和多巴胺的正性肌力反应期间显著抑制功能。这种负性肌力作用似乎具有选择性，因为维拉帕米并未改变对PESP的反应。
