Reduced beta-agonist sensitivity in single atrial cells from failing human hearts.
Human myocytes were isolated from right atrial appendage, and contractile responses to inotropic agents were studied. Responses to inotropic agents of cells isolated from patients with mild heart disease [New York Heart Association (NYHA) classes I and II] were compared with those of myocytes from rabbit atria. Maximally effective concentrations of calcium, forskolin, and isoproterenol increased contraction amplitude to a similar extent (11.9, 11.5, and 11.3% change in cell length, respectively), but histamine produced a smaller effect (7.1%). The maximum responses of rabbit atrial cells to calcium (18.5%) and isoproterenol (15.0%) were significantly greater than human. In human cells, the velocity of contraction or relaxation was accelerated more by isoproterenol (P less than 0.05) or forskolin (P less than 0.01) than by high calcium. Only relaxation velocity was increased by isoproterenol in rabbit cells (P less than 0.05). Rabbit myocytes contracted and relaxed 10-30% faster than human (P less than 0.05). Cells from the atria of patients with New York Heart Association (NYHA) heart failure class III or IV were less responsive to isoproterenol than those from class I or II (P less than 0.01). Omitting data from patients who had been taking calcium-channel blockers or beta-adrenoceptor agonist or antagonist drugs did not affect the conclusions. Analysis of variance revealed a significantly greater between-patient than within-patient variation (P less than 0.001), indicating that cells from the same patient have a tendency to respond in a similar way. Responses to high calcium did not differ among NYHA classes. The effect of forskolin was not reduced in NYHA class III, although there was a decreased response in cells from two patients in NYHA class IV.(ABSTRACT TRUNCATED AT 250 WORDS)
Harding
S E
SE
Department of Cardiac Medicine, National Heart and Lung Institute, London, United Kingdom.
Jones
S M
SM
O'Gara
P
P
Vescovo
G
G
Poole-Wilson
P A
PA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002303:Cardiac Output, Low / Q000188:drug therapy / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002469:Cell Separation; D004232:Diuretics / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006325:Heart Atria; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology; D012016:Reference Values; D013318:Stroke Volume
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D004232:Diuretics; D007545:Isoproterenol; D002118:Calcium