Inotropic and lusitropic dysfunction in myocardium from patients with dilated cardiomyopathy.
Isometric force of contraction (DT), peak rate of tension increase (+T), peak rate of tension decrease (-T), time to peak tension (TPT), and time to half-relaxation (T 1/2 T) were measured in electrically driven human papillary muscle strips (New York Heart Association [NYHA] class IV heart transplants, dilated cardiomyopathy; nonfailing (NF) donor hearts, brain dead) (1 Hz, 37 degrees C) under basal conditions (1.8 mmol/L Ca2+) and after stimulation with isoprenaline, ouabain, and Ca2+. There was no difference in the isometric contraction (+T, -T, TPT, and T 1/2 T) between NYHA IV hearts and NF hearts under basal conditions. Inotropic stimulation above 300% of basal DT increased -T significantly more in NF hearts (p less than 0.05) compared with NYHA IV hearts. The effectiveness of ouabain and Ca2+ to increase DT was not significantly changed in NYHA IV hearts compared with NF hearts. The isoprenaline-mediated increase in DT was reduced (p less than 0.05) in NYHA IV hearts to a similar extent (70%) as beta-adrenoceptors were downregulated. When the rate of stimulation was increased to 3 Hz (force-frequency relationship), force of contraction increased only in NF preparations, whereas it decreased in NYHA IV myocardium (p less than 0.05). It was concluded that the contractile apparatus in terminally failing human myocardium is sufficient to maximally increase DT. During inotropic stimulation, abnormalities in diastolic rather than systolic contraction become evident. This may indicate abnormal intracellular Ca2+ handling.
Schwinger
R H
RH
Medizinische Klinik I, Universität München, Germany.
Böhm
M
M
Erdmann
E
E
D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010210:Papillary Muscles / Q000503:physiopathology; D011943:Receptors, Adrenergic, beta / Q000032:analysis
D011943:Receptors, Adrenergic, beta; D010042:Ouabain; D007545:Isoproterenol; D002118:Calcium