Phosphodiesterase inhibition by enoximone in preparations from nonfailing and failing human hearts.

摘要: The effects of enoximone (MDL 17043, Perfan, CAS 77671-31-9) on the activities phosphodiesterase (PDE) isoenzymes I-IV and force contraction were investigated in ventricular preparations isolated from failing (end-stage myocardial failure, NYHA IV) non-failing human hearts. In both tissues four PDE (PDE I-IV) with similar properties separated by DEAE-sepharose chromatography. did not differ between As compared to I (IC50 2100 mumol/l) II 2900 is a selective III (cGMP-inhibited PDE, IC50 5.9 IV (cGMP-insensitive 21.1 inhibitor. Milrinone, 3-isobutyl-1-methylxanthine (IBMX) UD-CG 212 Cl, derivative pimobendan, studied heart for comparison. Milrinone inhibited enoximone, revealing values inhibition (1.2 3.3 which about two orders magnitude lower than that (173 306 mumol/l). Cl was most potent 0.05 inhibitor tested I, 175, 181 40.8 mumol/l, resp.), whereas IBMX nonselectively 15.3, 26.2, 5.6, 5.8 respectively). trabeculae carneae nonfailing hearts increased only marginally 18.0 +/- 9.1% (n = 8) 24.5 8.7% 9) predrug value.(ABSTRACT TRUNCATED AT 250 WORDS)