Author + information
- Received February 6, 1984
- Revision received June 5, 1984
- Accepted June 15, 1984
- Published online November 1, 1984.
- Jack L. Martin, MD, FACC*,1,
- Mariell J. Likoff, MD, FACC1,
- Joseph S. Janicki, PhD1,
- Warren K. Laskey, MD1,
- John W. Hirshfeld Jr., MD, FACC1 and
- Karl T. Weber, MD, FACC1
- ↵*Address for reprints: Jack L. Martin, MD, 654 Ravdin Building, Hospita: of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104.
Cardiotonic agents may prove useful in the long-term treatment of chronic heart failure provided myocardial efficiency is enhanced and clinical status is improved. Accordingly, the short-term hemodynamic and clinical response to the phosphodiesterase inhibitor, MDL 17043, was evaluated. Intravenous increments of 0.05 mg/kg (maximal total 3 mg/kg) were given to a peak cardiac output response in 13 patients with New York Heart Association functional class IV heart failure secondary to ischemic or myopathic disease. Significant (p < 0.05) responses at peak effect (1.7 mg/kg) included an increase in cardiac output (3.5 to 4.6 liters/min) and heart rate (86 to 90 beats/min) and a decrease in pulmonary capillary wedge (25 to 17 mm Hg), mean arterial (85 to 78 mm Hg) and right atrial (10 to 7 mm Hg) pressures. Coronary sinus flow (measured in nine patients) increased (122 to 144 ml/min, p < 0.01) as did myocardial oxygen uptake (14.1 to 15.1 ml/min, p < 0.01), whereas myocardial extraction of oxygen (78 to 72%, p < 0.01) and lactate (24 to 9%, p < 0.01) decreased with three patients producing lactate at the time of their peak cardiac output response. Nine of the 12 patients given longterm oral therapy improved at least one functional class at 2 weeks. This improvement was sustained at 20 weeks in five patients.
Thus, MDL 17043 acutely improves the function of the failing heart. However, the decrease in oxygen extraction occurring with increased myocardial oxygen uptake suggests that intracoronary shunting may occur along with an increase in oxygen demand and contribute to myocardial anaerobiosis in some patients. Hence, to assure an optimal response in myocardial energetics to MDL 17043, individual dose titration and hemodynamic monitoring are recommended.
- Received February 6, 1984.
- Revision received June 5, 1984.
- Accepted June 15, 1984.
- American College of Cardiology Foundation