title: CI-930, a new cardiotonic and vasodilating agent: hemodynamic comparison to dobutamine and long-term clinical effects.
abstract: The hemodynamic and clinical effects of parenteral and oral CI-930, a new phosphodiesterase type III inhibitor with combined vasodilator and inotropic properties, were studied in 12 patients with severe congestive heart failure refractory to therapy including captopril. The maximum response to dobutamine was also determined. Intravenous CI-930 increased cardiac index from 1.73 +/- 0.48 to 2.38 +/- 0.55 L/min/m2, and reduced pulmonary capillary wedge pressure from 19.2 +/- 7.9 to 12.5 +/- 6.4 mm Hg, mean right atrial pressure from 7.5 +/- 6.3 to 3.6 +/- 4.0 mm Hg, and systemic vascular resistance from 2288 +/- 860 to 1711 +/- 611 dynes . sec . cm-5 (p less than 0.001 for all). Heart rate and mean systemic arterial pressure were unchanged. The increment in cardiac index produced by dobutamine was higher than for CI-930, 2.68 +/- 0.55 vs 2.38 +/- 0.55 L/min/m2, p less than 0.001. However, reduction in pulmonary capillary wedge pressure tended to be less with dobutamine, 15.7 +/- 7.9 vs 12.5 +/- 6.4 mm Hg (NS). Hemodynamic benefits of oral CI-930 were equivalent to that of the parenteral drug. Duration of action was 9 to 12 hours. Chronic therapy resulted in subjective improvement in approximately 50% of patients. Exercise capacity, assessed by maximum oxygen consumption, was unchanged, 8.4 +/- 3.3 vs 9.8 +/- 3.4 ml/kg/min (NS). No overt laboratory manifestations of toxicity were observed.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: D
authors.initials: D
authors.lastname: Mancini
authors.forename: G
authors.initials: G
authors.lastname: Keren
authors.forename: E H
authors.initials: EH
authors.lastname: Sonnenblick
authors.forename: T H
authors.initials: TH
authors.lastname: LeJemtel
mesh_terms: D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004280:Dobutamine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011724:Pyridazines / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D004280:Dobutamine; C042528:4,5-dihydro-6-(4-(imidazol-1-yl)phenyl)-5-methyl-3(2H)-pyridazinone