Activation of Phosphorylase by Cyclic AMP without Augmentation of Contractility in the Perfused Guinea Pig Heart
Why the study?
Does increased intracellular cyclic AMP directly augment myocardial contractility in isolated guinea pig hearts?
Population
Isolated guinea pig hearts
Comparison
Perfusion with media containing 10^-4 M cyclic… vs Control, DMSO alone, or 5'-AMP with DMSO
Design
Preclinical
Authors
Discussion
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Implication
cAMP elevation alone does not increase contractility in isolated hearts; supports consensus that catecholamine inotropy is not mediated by direct cAMP action on the contractile apparatus.
Key Points
- To determine whether intracellular cyclic AMP directly augments myocardial contractility in the absence of adrenergic stimulation.
- Perfused isolated guinea pig hearts with media containing 10^-4 M cyclic AMP or adenine nucleotides, with or without 3% dimethylsulfoxide (DMSO) to facilitate cellular uptake.
- Measured heart rate, left ventricular pressure, and dP/dt in isovolumic preparations while fluorometrically assaying phosphorylase b to a transformation as a marker of cyclic AMP activity.
- Phosphorylase activation increased from a control level of 16.5±1.44% (N=12) to 40.0±3.1% (N=19) following perfusion with 10^-4 M cyclic AMP plus 3% DMSO.
- Perfusion with 10^-4 M cyclic AMP with or without DMSO modestly depressed left ventricular pressure and dP/dt, even when heart rate was held constant by electrical pacing.
Structured PICO
Does increased intracellular cyclic AMP directly augment myocardial contractility in isolated guinea pig hearts?
P
Population
Isolated guinea pig hearts
I
Intervention
Perfusion with media containing 10^-4 M cyclic AMP with or without 3% dimethylsulfoxide (DMSO)
C
Comparator
Control, DMSO alone, or 5'-AMP with DMSO
O
Outcome
Myocardial contractility (left ventricular pressure and dP/dt) and phosphorylase b to a transformationsurrogate
Increased intracellular cyclic AMP does not directly increase myocardial contractility, suggesting that the positive inotropic effect of catecholamines is not mediated by a direct action of cyclic AMP on the contractile apparatus.
Cite This Study
Kjekshus et al. (1971) studied this question.