Abnormal intracellular calcium handling, a major cause of systolic and diastolic dysfunction in ventricular myocardium from patients with heart failure.

摘要: Intracellular Ca2+ release and reuptake are necessary for normal contraction relaxation of the human heart. transients were recorded with aequorin during isometric myocardium from patients end-stage heart failure. In contrast to controls, contractions muscles failing hearts markedly prolonged, exhibited two distinct components. Muscles showed a diminished capacity restore low resting level diastole. These data obtained in actively contracting suggest that intracellular handling is abnormal might cause both systolic diastolic dysfunction The inotropic effectiveness drugs act increase levels cyclic adenosine monophosphate (AMP), such as beta-adrenergic agonists phosphodiesterase inhibitors, was reduced contrast, stimulation by AMP-independent mechanisms, cardiotonic steroids DPI 201-106, preserved. Stimulation AMP production adenylate cyclase activator forskolin restored response inhibitors. studies indicate an abnormality may be fundamental defect failure diminish agents depend on generation this nucleotide positive effect. Moreover, deficient seems, at least part, account reversal force-frequency relation characterizes myocardium. Of interest, direct measurement total cellular content protein kinase activity did not reveal significant differences between control myopathic tissue, suggesting presence ventricular muscle physiologically compartmentalized pools AMP. Finally, changes sensitivity contractile apparatus also seem play important role differential responsiveness versus