RO13-6438, a new inotrope-vasodilator: systemic and coronary hemodynamic effects in congestive heart failure.
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.
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011799:Quinazolines / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use
D002316:Cardiotonic Agents; D011799:Quinazolines; D014665:Vasodilator Agents; C040850:quazinone; D009638:Norepinephrine