Greenberg S, Touhey B, Paul J
Department of Pharmacology, Berlex Laboratories, Inc., Cedar Knolls.
Am Heart J. 1990 Jun;119(6):1355-66. doi: 10.1016/s0002-8703(05)80186-3.
BTS 49465 (flosequinan), a putative selective, balanced arterial and venous vasodilator, displays positive inotropic effects in doses lower than those producing vasodilation. Thus rather than unloading the myocardium, flosequinan may increase myocardial work and oxygen consumption (MVO2), and may adversely affect the patient with myocardial ischemia or compromised coronary blood flow. This study compared the effects of flosequinan with milrinone, a mixed positive inotropic agent and vasodilator, and with nitroprusside (SNP), a standard direct-acting vasodilator, on myocardial dP/dT, MVO2, and myocardial energetics in the normal pentobartital-anesthetized dog. The effect of flosequinan on myocardial work was also evaluated in the dog with propranolol-induced heart failure (PIHF). Fifteen minutes after intraduodenal (id) administration of flosequinan (0.3, 1.0, and 3.0 mg/kg) to seven dogs, mean myocardial dP/dT was increased by 11%, 27%, and 54%, respectively, whereas stroke MVO2 was increased by 10%, 24%, and 47%, respectively. Doses of flosequinan greater than 0.3 mg/kg decreased left ventricular (LV) work but LV efficiency decreased in a dose-related manner. Milrinone (0.1, 0.3, and 1.0 mg/kg, id) increased LV dp/dt by 34%, 68%, and 104% above basal values, while increasing stroke MVO2 by 24%, 106%, and 249%, respectively (n = 7). LV work and LV efficiency decreased after each dose of milrinone. SNP (0.001, 0.003, and 0.01 mg/kg/min, intravenously) did not increase dP/dT but decreased LV work by 28%, 42%, and 46% (n = 5). In animals with PIHF, flosequinan (1 and 3 mg/kg, id) increased LV dP/dT 58% and 87% and increased LV work by 58% and 76% above control values. It was concluded that (1) flosequinan is a positive inotropic agent as well as a vasodilator; (2) in the normal animal the energy cost of positive inotropic activity is less with flosequinan than with milrinone, despite the lesser vasodilating action of the former; and (3) in the animal with a depressed myocardium, flosequinan may adversely affect myocardial work and wall tension.
BTS 49465（氟司喹南）是一种假定的选择性、平衡的动静脉血管扩张剂，在低于产生血管扩张的剂量下显示出正性肌力作用。因此，氟司喹南可能不会减轻心肌负荷，反而会增加心肌做功和氧耗（MVO2），并可能对心肌缺血或冠状动脉血流受损的患者产生不利影响。本研究比较了氟司喹南与米力农（一种混合的正性肌力药和血管扩张剂）以及硝普钠（SNP，一种标准的直接作用血管扩张剂）对正常戊巴比妥麻醉犬的心肌dP/dT、MVO2和心肌能量代谢的影响。还评估了氟司喹南对普萘洛尔诱导的心力衰竭（PIHF）犬心肌做功的影响。给7只犬十二指肠内（id）给予氟司喹南（0.3、1.0和3.0mg/kg）15分钟后，平均心肌dP/dT分别增加了11%、27%和54%，而每搏MVO2分别增加了10%、24%和47%。大于0.3mg/kg的氟司喹南剂量降低了左心室（LV）做功，但LV效率呈剂量相关下降。米力农（0.1、0.3和1.0mg/kg，id）使LV dp/dt比基础值增加了34%、68%和104%，同时每搏MVO2分别增加了24%、106%和249%（n = 7）。每次给予米力农后，LV做功和LV效率均下降。SNP（0.001、0.003和0.01mg/kg/min，静脉内）未增加dP/dT，但使LV做功降低了28%、42%和46%（n = 5）。在患有PIHF的动物中，氟司喹南（1和3mg/kg，id）使LV dP/dT增加了58%和87%，使LV做功比对照值增加了58%和76%。得出的结论是：（1）氟司喹南是一种正性肌力药也是一种血管扩张剂；（2）在正常动物中，尽管氟司喹南的血管扩张作用较小，但其正性肌力活性的能量消耗比米力农少；（3）在心肌功能低下的动物中，氟司喹南可能对心肌做功和壁张力产生不利影响。
