Cardiovascular effects of a phosphodiesterase III inhibitor in the presence of carvedilol in dogs.
The aim of this study was to determine whether dobutamine, dopamine, or milrinone (a phosphodiesterase [PDE] III inhibitor) would support cardiac function that had been attenuated by administration of the beta-blocker, carvedilol (0.2, 0.4, or 0.8 mg/kg). Hemodynamic and cardiac parameters including the heart rate (HR), left-ventricular fractional shortening (FS), and arterial pressure were measured in six healthy dogs without cardiac disease. Carvedilol did not affect FS or arterial pressure, but decreased the HR significantly. The positive inotropic and chronotropic responses to dobutamine and dopamine were attenuated by carvedilol, whereas arterial pressure was unaffected. Milrinone did not affect the HR and decreased arterial pressure, whereas FS was significantly greater both in the control and carvedilol-treated groups. Although milrinone affect the negative chronotropic effects of carvedilol, milrinone increased FS and prevented the decrease in arterial pressure. These results suggest that inhibition of PDE III preserves cardiac contractility and hemodynamic function in the presence of carvedilol.
Uechi
Masami
M
Veterinary Teaching Hospital, School of Veterinary Medicine & Animal Science, Kitasato University, Aomori, Japan.
Hori
Yasutomo
Y
Fujimoto
Keiko
K
Ebisawa
Takashi
T
Yamano
Shigeki
S
Maekawa
Shinnosuke
S
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D000077261:Carvedilol; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004280:Dobutamine / Q000494:pharmacology*; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D020105:Milrinone / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D004280:Dobutamine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D020105:Milrinone; D004298:Dopamine