Effects of forskolin on left ventricular function in dilated cardiomyopathy.
The adenylate cyclase activator 17 beta-acetoxy-8, 13-epoxy-1 alpha,6 beta,9 alpha-trihydroxylabd-14-en-11-one (forskolin) was studied for its beneficial effect as therapeutic agent for the treatment of dilated cardiomyopathy (DCM). In 7 DCM-patients with normal (group A) and 8 DCM-patients with pathological dP/dtmax-values (group B), we analyzed serially (computer-assisted) the pressure/volume (P/V) effects as P/V-loops (microtip catheter/Tc-99m scintigraphy) and on-line MV02 (indirectly: Bretschneider equation) under dobutamine, 10 micrograms/kg/min i.v., and forskolin, 3 micrograms/kg/min i.v. For the total group (A + B) there was no change of contractility during forskolin (p greater than 0.05); with dobutamine, however, it rose by an average of +25%. The preload decline was more pronounced with forskolin (LVEDP by -27%) as compared to dobutamine (by-19%); while left ventricular (LV-)function improved moderately only with forskolin (by +9%) and significantly (by +34%) with dobutamine. Thus, forskolin improved LV-function primarily via reduction of preload in DCM-hearts and without rising metabolic costs. Beneficial hemodynamic effects with forskolin are quantitatively less as compared to those with dobutamine (accompanied by higher MVO2-costs). It is concluded that residual myocardial reserves in DCM are mobilized by dobutamine rather than forskolin. Serial P/V-loop and on-line MVO2 registration aided in the demonstration of forskolin efficacy as compared to dobutamine.
D000792:Angiography; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D005576:Colforsin / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects
D005576:Colforsin; D004280:Dobutamine