Petein M, Heppner B, Bache R J, Cohn J N, Pierpont G L
J Pharmacol Exp Ther. 1987 Jun;241(3):956-60.
This study compares the effects of piroximone (MDL 19,205), a new inotropic agent, with dobutamine in dogs with congestive heart failure. With dobutamine, (15 micrograms/kg/min) left ventricular (LV) dp/dt increased from 2220 +/- 215 (mean +/- S.E.M.) to 2815 +/- 280 mm Hg/sec and cardiac index increased from 2.9 +/- 0.2 to 3.7 +/- 0.4 liters/min/m2, whereas LV filling pressure was essentially unchanged (18.7 +/- 2.6-16.3 +/- 2.4 mm Hg). The hemodynamic effects of piroximone (50 micrograms/kg/min) were more pronounced. LV dp/dt increased from 2615 +/- 260 to 3760 +/- 410 mm Hg/sec and cardiac index from 3.0 +/- 0.1 to 4.4 +/- 0.6 liters/min/m2, whereas LV filling pressure decreased from 15.6 +/- 2.4 to 6.4 +/- 1.8 mm Hg (all P less than .05). Systemic vascular resistance index decreased from 2730 +/- 225 to 1905 +/- 256 dynes sec cm-5 m-2. Regional blood flow to the myocardium increased 48% with dobutamine and 24% with piroximone, whereas skeletal muscle flow increased 59% with dobutamine and 36% with piroximone. Renal blood flow remained unchanged with either drug. We conclude that piroximone is an inotropic agent with vasodilator properties that has an interesting hemodynamic profile somewhat similar to that of dobutamine but with the advantage of being orally active; therefore piroximone could be useful in the treatment of heart failure.
本研究比较了新型正性肌力药物吡罗昔酮(MDL 19,205)与多巴酚丁胺对充血性心力衰竭犬的影响。使用多巴酚丁胺(15微克/千克/分钟)时,左心室(LV)dp/dt从2220±215(平均值±标准误)增加到2815±280毫米汞柱/秒,心脏指数从2.9±0.2增加到3.7±0.4升/分钟/平方米,而左心室充盈压基本不变(18.7±2.6 - 16.3±2.4毫米汞柱)。吡罗昔酮(50微克/千克/分钟)的血流动力学效应更为显著。左心室dp/dt从2615±260增加到3760±410毫米汞柱/秒,心脏指数从3.0±0.1增加到4.4±0.6升/分钟/平方米,而左心室充盈压从15.6±2.4降低到6.4±1.8毫米汞柱(所有P值均小于0.05)。全身血管阻力指数从2730±225降低到1905±256达因秒厘米⁻⁵米⁻²。多巴酚丁胺使心肌区域血流量增加48%,吡罗昔酮使其增加24%,而多巴酚丁胺使骨骼肌血流量增加59%,吡罗昔酮使其增加36%。两种药物对肾血流量均无影响。我们得出结论,吡罗昔酮是一种具有血管舒张特性的正性肌力药物,其血流动力学特征与多巴酚丁胺有些相似,但具有口服活性的优势;因此,吡罗昔酮可能对心力衰竭的治疗有用。