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Cardiovascular effects of medorinone in β‐adrenoreceptor‐blocked and non‐blocked anesthetized dogs
Author(s) -
Lee King C.,
Ezrin Alan M.,
Pagani Edward D.,
Canniff Paul C.,
Hamel Douglas W.,
Fort Dorothy J.,
Silver Paul J.
Publication year - 1990
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430210205
Subject(s) - preload , chronotropic , hemodynamics , chemistry , fissipedia , heart rate , medicine , phenylephrine , endocrinology , blood pressure , ventricular pressure , anesthesia
The hemodynamic effects of the low K m cAMP peak III PDE inhibitor medorinone (0.01–0.3 mg/kg, i. v. ) were evaluated in anesthetized dogs in the presence and absence of β‐adrenoreceptor blocked. Medorinone increased the peak derivative of left ventricular pressure (+ dP/dt) in non‐blocked (all doses) and β‐blocked dogs (≥0.03 mg/kg) (2,766±259 and 1,403±262 mm Hg/sec, respectice max. changes). Heart rate (HR) was increased by medorinone in non‐blocked (≥0.1 mg/kg) and β‐blocked dogs (≥0.03 mg/kg) (77.4±8.9 and 25.5±4.3 beats/min, respective max. changes). In non‐blocked dogs only, medorinone (all doses) decreased left ventricular end‐diastolic pressure (LVEDP) (7.7±1.7 mm Hg, max. change). Mean arterial pressure (MAP) was similarly decreased by medorinone (<0.03 mg/kg) in β‐blocked and non‐blocked dogs (max. approx. −27 mm Hg). Medorinone did not affect cardiac output or renal blood flow. The hemodynamics of medorinone and milrinone (another peak III PDE inhibitor) in non‐blocked dogs were similar, except meddorinone was less potent in increasing +dP/dt (2,766±259 vs. 3,747±388, max. changes) and more potent in reducing LVEDP (−7.7±1.7 vs. −1.8±1.2 mm Hg, max. changes). In conclusion, medorinone similarly reduced MAP, but more effectively decreased preload, increased inotropy and chronotropy in non‐blocked than β‐blocked anesthetized dogs. Medorinone is more potent in reducing preload, but less potent in enhancing inotropy when compared to milrinone in anesthetized dogs.