Disparity between improvement in left ventricular function and changes in clinical status and exercise capacity during chronic enoximone therapy.

Twenty patients with moderately severe congestive heart failure were randomized to chronic enoximone (n = 10) or placebo (n = 10) therapy in a double-blind manner and serially evaluated over a 16-week-period. The purpose of the study was to determine if the addition of standard doses (1 and 2 mg/kg) of this new phosphodiesterase inhibitor to conventional therapy (digitalis and diuretics) would alter the clinical and laboratory course of this patient population. Except for a transient improvement in the quality of life score, none of the symptomatology indicators were significantly affected by enoximone. Similarly, maximal exercise capacity was not altered. Enoximone did elicit a statistically significant augmentation of echocardiographic, radionuclide angiographic, and systolic time interval parameters of left ventricular function. These enoximone-induced effects were accompanied by a significant increase (7% to 11%) in resting heart rate. Enoximone is capable of improving ventricular function when added to digitalis-diuretic therapy in moderately severe congestive heart failure. While individual patients may benefit from enoximone, the ability of standard doses of this agent to improve symptoms and exercise capacity over a 16-week period appears somewhat limited in a moderately severe heart failure population as a whole. Furthermore, a disparity between improvement in ventricular function parameters and changes in clinical status and exercise performance is apparent in this heart failure population.

Usefulness of a free radical scavenger in preventing doxorubicin-induced heart failure in dogs.

This study was designed to investigate whether either of 2 dosage schedules of N-acetylcysteine (NAC) was effective in preventing chronic doxorubicin-induced heart failure in dogs. Thirty-eight dogs were randomly assigned to 1 of 4 groups: controls, 10 dogs; doxorubicin only, 12 dogs; doxorubicin + low dose NAC, 8 dogs; and doxorubicin + high dose NAC, 8 dogs. All dogs except the controls received 1 mg/kg of doxorubicin weekly for 8 weeks and then every other week for 8 weeks. The doxorubicin + low-dose NAC group received 140 mg/kg of NAC 30 minutes before each dose of doxorubicin. The doxorubicin + high-dose NAC group received NAC before and then twice a day for 5 days. Systolic time intervals and echocardiograms were obtained weekly; cardiac catheterization was performed at the conclusion of the study. Of the 38 dogs in the study, 9 died; all deaths were in the doxorubicin treatment groups. The incidence of death was not different between the doxorubicin-only, the doxorubicin + low-dose and the doxorubicin + high-dose NAC groups. The noninvasive and the invasive and the catheterization data generally revealed poorer cardiac function of the doxorubicin treatment groups than in controls. However, no significant differences existed between the doxorubicin-only and doxorubicin + low-dose and doxorubicin + high-dose NAC groups. In conclusion, NAC in a low- or high-dose regimen did not significantly ameliorate doxorubicin cardiac toxicity. Because NAC is a free radical scavenger, perhaps doxorubicin cardiac toxicity is not a result of free radical generation.

Nifedipine in congestive heart failure: effects on resting and exercise hemodynamics and regional blood flow.

Ten patients with moderate to severe congestive heart failure (CHF) underwent central and regional hemodynamic measurements at rest and central hemodynamic measurements during exercise before and after the oral administration of nifedipine (0.2 mg/kg). Nifedipine significantly decreased systemic blood pressure, systemic vascular resistance, pulmonary artery pressure, pulmonary vascular resistance, and pulmonary capillary wedge pressure. Stroke volume and cardiac output increased after nifedipine. The measured parameters of left ventricular inotropy did not change significantly for this calcium channel blocker. While blood flow to renal, hepatic, and limb vascular beds increased (p less than 0.05 for renal and limb) after nifedipine, only limb blood flow increased in proportion to the increase in cardiac output, suggesting preferential dilatation of limb vasculature. Although initial-dose nifedipine did not increase exercise duration, it elicited an improvement in exercise hemodynamics by reducing systemic vascular resistance and pulmonary capillary wedge pressure and increasing stroke volume and cardiac output. The calcium channel blocker, nifedipine, can be administered safely in the setting of ventricular failure and appears to favorably alter resting and exercise hemodynamics. A select number of patients with CHF may benefit from its long-term administration.