Key result
In isolated guinea pig papillary muscles, milrinone-induced positive inotropy significantly correlated with increases in cAMP content (r=0.72, p<0.05) and cAPK activation (r=0.79, p<0.001).
Population
Isolated guinea pig cardiac muscle (papillary muscles)
Comparison
Milrinone (0.1-1000 microM) vs Isoproterenol, ouabain, and Bay K-8644
Design
Preclinical
Authors
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Supports cAMP/cAPK mechanism of milrinone inotropy in guinea pig model; leaves open translation to human heart failure therapy.
p-value: p=<0.05
Milrinone mediates positive inotropy in cardiac muscle through selective phosphodiesterase isozyme inhibition and subsequent activation of the cAMP/cAPK system.
Silver et al. (1989) studied this question. Milrinone vs. isoproterenol, ouabain, or Bay K-8644 was evaluated on Correlation between isometric force development and cAMP content or cAPK activity ratio (p=<0.05). In isolated guinea pig papillary muscles, milrinone-induced positive inotropy significantly correlated with increases in cAMP content (r=0.72, p<0.05) and cAPK activation (r=0.79, p<0.001).
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