Decreased inotropic but relatively preserved relaxation response to cyclic adenosine monophosphate-dependent agents in myopathic human myocardium
Increased intracellular concentrations of cyclic adenosine monophosphate (AMP) stimulate a positive inotropic and lusitropic response in healthy myocardial tissue. Heart failure results in an attenuated inotropic response to cyclic AMP-dependent agents. This study compares the inotropic versus relax...
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Published in | Journal of cardiac failure Vol. 2; no. 4; pp. 285 - 292 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.12.1996
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Subjects | |
Online Access | Get full text |
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Summary: | Increased intracellular concentrations of cyclic adenosine monophosphate (AMP) stimulate a positive inotropic and lusitropic response in healthy myocardial tissue. Heart failure results in an attenuated inotropic response to cyclic AMP-dependent agents. This study compares the inotropic versus relaxation response to cyclic AMP-dependent and cyclic AMP-independent agents in myocardium from patients with end-stage heart failure and control patients without heart failure.
Fifty-four control and 59 myopathic human ventricular trabeculae, 1 mm or less in diameter were placed in physiologic saline, 2.5 mM Ca
2+, and stretched to the length at which maximal isometric force developed at 30°C, 0.33 Hz. Dose-response curves plotted as percentage change from baseline versus concentration of drug were determined for acetylstrophanthidin, isoproterenol, isobutylmethylxanthine, and milrinone. Acetylstrophanthidin, a cyclic AMP-independent agent, showed similar increases in peak tension relative to baseline over the entire dose range tested for both control and myopathic heart muscle; its effect on relaxation of control and failing cardiac muscle was equivalent over the dose range tested. In contrast, the inotropic actions of the cyclic AMP-dependent agents, isoproterenol and the phosphodiesterase inhibitors, were significantly decreased in myopathic muscle compared with control muscle, but effects on relaxation in the control and myopathic groups remained relatively preserved.
A relatively preserved relaxant effect is associated with the cyclic AMP-dependentagents, despite significant diminution of their inotropic effects. Thus, in advanced heart failure, patients may continue to benefit from the lusitropic effects of the cyclic AMP-dependent agents, even when the inotropic effects of these agents are severely attenuated. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1071-9164 1532-8414 |
DOI: | 10.1016/S1071-9164(96)80015-7 |