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CI-930, a new cardiotonic and vasodilating agent: hemodynamic comparison to dobutamine and long-term clinical effects
D Mancini1, G Keren, E H Sonnenblick
1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Insights
CI-930, a phosphodiesterase type III inhibitor, improved hemodynamics in severe heart failure patients. Both oral and intravenous CI-930 offered benefits, with subjective improvements in about half of patients.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Severe congestive heart failure (CHF) patients often have refractory symptoms despite conventional therapies.
- Phosphodiesterase type III (PDE III) inhibitors offer potential therapeutic benefits through combined vasodilator and inotropic actions.
Purpose of the Study:
- To evaluate the hemodynamic and clinical effects of a novel PDE III inhibitor, CI-930, in patients with severe CHF.
- To compare the efficacy of CI-930 with dobutamine, a standard inotropic agent.
Main Methods:
- A study involving 12 patients with severe CHF refractory to existing treatments.
- Administration of intravenous and oral CI-930, with subsequent hemodynamic monitoring.
- Determination of maximal response to dobutamine for comparative analysis.
Main Results:
- Intravenous CI-930 significantly increased cardiac index and reduced pulmonary capillary wedge pressure, right atrial pressure, and systemic vascular resistance.
- Oral CI-930 demonstrated equivalent hemodynamic benefits to the intravenous form, with a duration of action of 9-12 hours.
- While dobutamine produced a greater increase in cardiac index, CI-930 showed a comparable or greater reduction in pulmonary capillary wedge pressure.
Conclusions:
- CI-930 exhibits significant hemodynamic benefits in severe congestive heart failure patients, with both parenteral and oral administration showing efficacy.
- Chronic CI-930 therapy led to subjective clinical improvement in approximately 50% of patients without significant adverse effects.
- CI-930 represents a promising therapeutic option for managing severe, refractory congestive heart failure.
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.