Comparison of the Cardiovascular Effects of Intracellular Cyclic Adenosine 3',5'-Monophosphate (cAMP)-Modulating Agents in Isoflurane-Anesthetized Cats

Abstract

The inotropic, chronotropic, and vasodilatory effects of five commonly used cyclic adenosine 3',5'-monophosphate (cAMP)-modulating agents were evaluated. Hemodynamic functions were measured continuously in isoflurane-anesthetized cats during infusion of the following: dobutamine (DOB; 2.5, 5 and 10 μg/kg/min; n=8), dopamine (DOP; 1.25, 2.5, 5 and 10 μg/kg/min; n=5), milrinone (MIL; 2.5, 5 and 10 μg/kg/min; n=8), 6-(3-dimethyl-aminopropionyl) forskolin hydrochloride (COL; 0.2, 0.4, 0.8, and 1.6 μg/kg/min; n=7), and bucladesine sodium (BUC; 10, 20, and 40 μg/kg/min; n=9). At the highest infusion rate, DOB and DOP produced the greatest positive inotropic (increase in left ventricular (LV) dP/dt = 89 ± 4% and 75 ± 6%, respectively) and chronotropic (increase in heart rate (HR) = 42 ± 4% and 22 ± 6%, respectively) effects. MIL and COL produced similar albeit less pronounced positive inotropic (increase in LV dP/dt = 18 ± 3% and 22 ± 6%, respectively) and chronotropic (increase in HR = 13 ± 4% and 21 ± 4%, respectively) effects. Both also had significant vasodilatory effects (decrease in peripheral resistance (PR) = -30 ± 2% and -35 ± 7%, respectively). In contrast, BUC produced only vasodilatation (decrease in PR = -33 ± 6%). Hence, MIL, COL, and BUC had significant vasodilatory effects and less-pronounced inotropic effects than the catecholamines DOB and DOP. The vasodilatory effects of non-catecholamine drugs for treatment of congestive heart failure should translate into beneficial decreases in both pre-load and after-load. In contrast, the strong inotropic effects of DOB and DOP should be beneficial in the treatment of acute heart failure and anesthetic crisis.