Acute hemodynamic and hormonal effects of CI-930, a new phosphodiesterase inhibitor, in severe congestive heart failure.
The phosphodiesterase inhibitor CI-930 hydrochloride exerts a positive inotropic and vasodilator effect in experimental animals. The acute hemodynamic and hormonal effects of intravenous CI-930 were studied in 9 patients with severe congestive heart failure. At 60 minutes of drug infusion, there was an increase in cardiac index (2.7 +/- 0.9 vs 2.0 +/- 0.7 liters/min/m2, p less than 0.01) and positive dP/dt (1,390 +/- 470 vs 1,100 +/- 300 mm Hg/s, p less than 0.02). Additionally, there were decreases in mean systemic arterial (78 +/- 16 vs 86 +/- 15 mm Hg, p less than 0.01), mean right atrial (5 +/- 3 vs 9 +/- 4 mm Hg, p less than 0.02), mean pulmonary arterial (27 +/- 11 vs 37 +/- 9 mm Hg, p less than 0.01) and LV end-diastolic (19 +/- 8 vs 28 +/- 6 mm Hg, p less than 0.01) pressures. Heart rate did not change (97 +/- 17 vs 97 +/- 22 beats/min). The inotropic response correlated significantly (r = 0.70, p less than 0.05) with the dose of CI-930. Plasma renin activity did not change significantly (from 16 +/- 9 to 23 +/- 15 ng/ml/hour), nor did plasma norepinephrine or arginine vasopressin levels. The plasma atrial natriuretic peptide level decreased (from 153 +/- 97 to 83 +/- 35 pg/ml, p less than 0.02). These findings suggest that intravenous CI-930 hydrochloride is a useful therapeutic agent in congestive heart failure and that its use does not appear to further activate potentially deleterious hormonal systems.
D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011724:Pyridazines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors
D006728:Hormones; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; C042528:4,5-dihydro-6-(4-(imidazol-1-yl)phenyl)-5-methyl-3(2H)-pyridazinone