Cardiovascular effects of forskolin and phosphodiesterase-III inhibitors

In the first part of this presentation, data is reported on the hemodynamic effects of forskolin given to patients with dilated cardiomyopathy in a concentration of 3 micrograms/kg/min and 4 micrograms/kg/min. At the lower dosage, forskolin had no effect on dP/dtmax, cardiac index, ejection fraction, or myocardial oxygen consumption. With small dosages of dobutamine, however, an increase of all four parameters has been observed in the same group of patients. Systemic vascular resistance and left ventricular enddiastolic pressure fell with forskolin given at the lower concentration. Forskolin administered at a dosage of 4 micrograms/kg/min induced an increase in dP/dtmax by 19% and a 16% rise in heart rate. However, these changes were associated with symptomatic flush syndromes. Therefore, forskolin may serve as a vasodilating substance in lower concentrations, but cannot be used as a positive inotropic compound because of the subjective symptoms. In the second part, a study is reported in which an anti-ischemic effect of the phosphodiesterase inhibitor enoximone was observed in patients with proven significant coronary heart disease. With respect to the hemodynamic parameters, the most striking findings were the decreases in left ventricular enddiastolic pressure and systemic vascular resistance. Furthermore, when left ventricular stroke work index was plotted as a function of the left ventricular enddiastolic pressure, enoximone shifted the left ventricular function curve to the left. Therefore, the anti-ischemic effect of enoximone may not only be due to a reduction in preload and afterload but may rather reflect an effect on diastolic compliance. Studies with intracoronary injections of enoximone and animal experiments support this hypothesis.