Daly P A, Chatterjee K, Viquerat C E, Parmley W W, Curran D, Scheinbaum M, Anderson S
Am J Cardiol. 1985 Jun 1;55(13 Pt 1):1539-44. doi: 10.1016/0002-9149(85)90969-5.
Systemic and coronary hemodynamics and transmyocardial norepinephrine release were determined before and after oral administration of RO13-6438, a new inotrope-vasodilator agent, in 12 patients with severe chronic heart failure unresponsive to conventional and vasodilator therapy. Improvement in left ventricular (LV) function was evident from a marked increase in cardiac index (from 2.09 +/- 0.45 to 3.30 +/- 0.73 liters/min/m2, p less than 0.01), stroke volume index (from 23 +/- 7 to 36 +/- 11 ml/m2, p less than 0.01), and stroke work index (from 23 +/- 11 to 36 +/- 14 g-m/m2, p less than 0.01), and concomitant fall in pulmonary capillary wedge pressure (from 26 +/- 7 to 16 +/- 8 mm Hg, p less than 0.01). Myocardial oxygen consumption did not change significantly (from 15.3 +/- 6.8 to 14.9 +/- 6.8 ml/min), but the ratio of minute work/myocardial oxygen consumption, an index of LV efficiency, increased significantly (p less than 0.05). Although average coronary sinus flow did not change, coronary sinus oxygen increased (from 3.2 +/- 0.8 to 4.2 +/- 1.5 vol%, p less than 0.05), and arterial-coronary sinus oxygen difference decreased (from 11.8 +/- 2.1 to 10.4 +/- 1.9 vol%, p less than 0.05), suggesting a primary vasodilating effect of RO13-6438 on the coronary vascular bed. Net transmyocardial norepinephrine release did not change despite the marked hemodynamic improvement. These findings suggest that RO13-6438 has the potential to cause marked improvement in LV function and LV efficiency in patients with severe, refractory congestive heart failure.
对12例对传统治疗和血管扩张剂治疗无效的严重慢性心力衰竭患者，在口服新型强心-血管扩张剂RO13 - 6438之前和之后，测定了全身和冠状动脉血流动力学以及经心肌去甲肾上腺素释放情况。左心室（LV）功能改善明显，表现为心脏指数显著增加（从2.09±0.45升至3.30±0.73升/分钟/平方米，p＜0.01）、每搏量指数（从23±7升至36±11毫升/平方米，p＜0.01）和每搏功指数（从23±11升至36±14克-米/平方米，p＜0.01），同时肺毛细血管楔压下降（从26±7降至16±8毫米汞柱，p＜0.01）。心肌耗氧量无显著变化（从15.3±6.8降至14.9±6.8毫升/分钟），但作为左心室效率指标的每分功/心肌耗氧量比值显著增加（p＜0.05）。虽然平均冠状窦血流量未变，但冠状窦血氧含量增加（从3.2±0.8升至4.2±1.5容积%，p＜0.05），动脉-冠状窦血氧差减小（从11.8±2.1降至10.4±1.9容积%，p＜0.05），提示RO13 - 6438对冠状动脉血管床有主要的血管扩张作用。尽管血流动力学有显著改善，但经心肌去甲肾上腺素的净释放量未变。这些发现表明，RO13 - 6438有潜力使严重难治性充血性心力衰竭患者的左心室功能和左心室效率得到显著改善。
