The blunted inotropic response to beta-adrenergic stimulation in failing human hearts may be causally related to an inadequate increase in cAMP content.
Highlights impaired cAMP response limiting inotropy in failing myocardium; leaves open therapeutic targeting in clinical HF.
We measured force of contraction and cAMP content in human isolated electrically driven right ventricular trabeculae carneae with and without the addition of isoprenaline (0.2 microM). Basal cAMP content was approximately 200% higher in preparations from nonfailing hearts than from hearts with end-stage myocardial failure. Isoprenaline was less effective in increasing force of contraction in failing (by approximately 100%) than in nonfailing cardiac preparations (by approximately 500%). With isoprenaline, cAMP content was approximately 50% lower in failing than in nonfailing preparations. We conclude that the reduced increase in force of contraction of failing human cardiac preparations with isoprenaline added may be causally related to an inadequately increased cAMP content.
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Danielsen et al. (1989) studied this question.
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