title: Beta-adrenoceptor function changes with age of subject in myocytes from non-failing human ventricle.
abstract: The contractile response to beta-adrenoceptor stimulation has been found to be reduced in single myocytes from failing human ventricle. A portion of that reduction was statistically related to the age of the patient. We have developed a method for obtaining viable contracting myocytes from small biopsies of human ventricle, enabling experiments to be performed on non-failing left ventricle from patients undergoing coronary artery surgery. These subjects are generally in an older age range than those we have previously obtained from donor hearts. The present study compares responses to isoproterenol and high Ca2+ between myocytes from older (> 50 years, n = 8) and younger (< 40 years, n = 5) subjects. Myocytes from older patients did not differ in their contraction amplitude (10.7 +/- 1.0 cf. 10.8 +/- 1.1% cell shortening), or contraction and relaxation velocities in high Ca2+ at a driving frequency of 0.2 Hz (32 degrees C). The sensitivity to isoproterenol, as determined from the EC50 value (concentration for half-maximal effect), was also similar between age groups (1.16 +/- 0.64 nM young, cf. 2.76 +/- 2.0 nM old), although higher than in myocytes from failing hearts (22.3 +/- 7.5 nM, n = 11). However, for the older group there was a significant depression in maximum contraction amplitude with isoproterenol (8.5 +/- 0.6 cf. 11.5 +/- 1.0% cell shortening, P < 0.05) and in the ratio between this and the maximum Ca2+ response (isoproterenol/Ca2+ ratio, 0.79 +/- 0.05 cf. 1.16 +/- 0.12, P < 0.05). Concomitantly, the maximum contraction and relaxation velocities achieved in the presence of isoproterenol were also depressed in older subjects (P < 0.02 for both). We conclude that age and/or coronary disease with unimpaired left ventricular function selectively reduces the maximum effect of isoproterenol but not the concentration at which this occurs.
authors.affiliation: Department of Cardiac Medicine, National Heart and Lung Institute, London, UK.
authors.forename: C H
authors.initials: CH
authors.lastname: Davies
authors.forename: N
authors.initials: N
authors.lastname: Ferrara
authors.forename: S E
authors.initials: SE
authors.lastname: Harding
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D003327:Coronary Disease / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D002118:Calcium