Arbogast R, Brandt C M, Fincker J L, Schechter P J
J Cardiovasc Pharmacol. 1986 Jan-Feb;8(1):82-9. doi: 10.1097/00005344-198601000-00014.
Piroximone (MDL 19,205), a new imidazolone derivative, was given intravenously to 14 patients with congestive heart failure (NYHA class II-III), while under constant daily doses of digitalis and diuretics. In the first 3 patients, we determined the dose safely eliciting a favorable hemodynamic response. The subsequent 11 patients received 1 mg/kg of piroximone intravenously, and the hemodynamic effects were compared with those of sodium nitroprusside (SN) at a dose-lowering mean blood pressure by 10-20 mm Hg. Piroximone increased heart rate (13.2 +/- 2.0 beats/min, mean +/- SEM) and lowered mean arterial pressure (9 +/- 2.3 mm Hg). Both agents reduced similarly wedge pressure (6.5 +/- 2.9 and 9 +/- 2.9 mm Hg, respectively, for SN and piroximone) and total peripheral resistance. Cardiac index was increased less by SN (15%) than piroximone (48%) (p less than 0.001), and stroke work index significantly enhanced only by piroximone (p less than 0.001). The changes in loading conditions induced by the two agents being similar, it is likely that piroximone not only acts by peripheral vasodilation, but also possesses positive inotropic properties. Myocardial oxygen demand, assessed indirectly by tension-time index, was not affected by piroximone. Thus, piroximone appears to combine well-balanced vasodilator and inotropic properties which make this new agent potentially very useful for the management of congestive heart failure.
匹罗昔酮(MDL 19,205)是一种新型咪唑啉酮衍生物,在14例充血性心力衰竭(纽约心脏协会II - III级)患者持续每日服用恒定剂量洋地黄和利尿剂的情况下,对其进行静脉给药。在最初3例患者中,我们确定了能安全引发良好血流动力学反应的剂量。随后的11例患者静脉注射1mg/kg匹罗昔酮,并将其血流动力学效应与硝普钠(SN)降低平均血压10 - 20mmHg时的效应进行比较。匹罗昔酮使心率增加(13.2±2.0次/分钟,平均值±标准误),并降低平均动脉压(9±2.3mmHg)。两种药物对楔压(SN和匹罗昔酮分别为6.5±2.9和9±2.9mmHg)和总外周阻力的降低作用相似。硝普钠使心脏指数增加15%,低于匹罗昔酮增加的48%(p<0.001),且仅匹罗昔酮能显著提高每搏功指数(p<0.001)。两种药物引起的负荷条件变化相似,匹罗昔酮可能不仅通过外周血管舒张起作用,还具有正性肌力特性。通过张力 - 时间指数间接评估的心肌需氧量不受匹罗昔酮影响。因此,匹罗昔酮似乎兼具平衡良好的血管舒张和正性肌力特性,这使得这种新药在充血性心力衰竭的治疗中可能非常有用。