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An improved model for assessment of positive inotropic activity in vitro
Author(s) -
Anderson William G.
Publication year - 1983
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430030506
Subject(s) - inotrope , ouabain , calcium , chemistry , amrinone , calcium in biology , tyramine , pharmacology , medicine , endocrinology , sodium , biochemistry , organic chemistry
Responses of guinea pig paced left atria to positive inotropic agents that probably act by different mechanisms were compared at two different calcium concentrations in vitro (1.25 and 2.50 mM). Consistently good results were obtained with isoproterenol, ouabain, amrinone, and 3‐isobutyl‐1‐methylxanthine only at the lower calcium concentration, which resulted in a greater percentage of responsive preparations, greater response discrimination, lower incidence of spontaneous and drug‐induced arrhythmias, and therefore a better quantitative assessment of concentration‐response relationships. Satisfactory responses were also obtained with the indirect‐acting agent tyramine and with the new agent, vardax. An excellent correlation between the magnitude of tension developed and the maximum rate of tension development was obtained for various inotropic stimuli. The partial beta agonists, prenalterol and dichloroisoproterenol, gave relatively poor responses under both sets of experimental conditions. It is concluded that the use of a low calcium concentration in the bathing medium enhances responsiveness to a variety of inotropic agents acting by different mechanisms, providing a useful and more reliable model for testing in vitro. It is suggested that a low external calcium concentration results in a smaller predrug sarcolemmal calcium flux, which may be markedly enhanced by inotropic agents.