Contractile responses of myocytes isolated from patients with cardiomyopathy.
Single cardiac myocytes isolated from failing and non-failing human ventricles were superfused at 32 degrees C and electrically stimulated at 0.2 Hz. Their contraction amplitude and velocities of contraction and relaxation were continuously during challenge with isoprenaline or high extracellular calcium. Action potentials were monitored with intracellular microelectrodes, and calcium transients followed using the fluorescent dye fura-2. Changes in contractility were correlated with severity of disease, as defined by New York Heart Association class, dose of diuretics, left ventricular ejection fraction and left ventricular end-diastolic pressure. Beta-adrenoceptor desensitization was detected in these cells as a decreased response to isoprenaline relative to that of calcium in the same cell. Significant correlations were obtained between reduction of beta-adrenoceptor sensitivity and all four indicators of disease severity. No correlation between the maximum contraction amplitude in high extracellular calcium and severity of disease was observed, the same was true for contraction and relaxation velocity in high calcium. Some significant decline in contractility with age of the patient was noted. Analysis with respect to aetiology of disease showed a subpopulation with dilated or hypertrophic cardiomyopathy where relaxation of the single cells was impaired. This was related to a prolonged calcium transient and action potential. Isoprenaline accentuated the lengthened second phase of relaxation, whereas high extracellular calcium reduced it. These interventions had similar effects on action potential duration. The actions of isoprenaline and calcium were similar on cells from failing and non-failing human hearts and on normal guinea-pig myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Cardiac Medicine, National Heart and Lung Institute, London, U.K.
S E
SE
Harding
K T
KT
MacLeod
S M
SM
Jones
G
G
Vescovo
P A
PA
Poole-Wilson
D000200:Action Potentials / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D009202:Cardiomyopathies / Q000473:pathology / Q000503:physiopathology*; D004558:Electric Stimulation; D006330:Heart Defects, Congenital / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000473:pathology*; D016277:Ventricular Function, Left / Q000502:physiology
D007545:Isoproterenol; D002118:Calcium