[Age-dependent regulation of cardiac glycoside receptors]

Specific binding of cardiac glycosides to their receptors precedes their actions on the myocardium. Thus changes in the number and affinity of these membrane bound receptors will vary the response to cardiac glycoside therapy and the incidence of side-effects. Several studies have reported an age-dependent decrease in the number of cardiac glycoside receptors in animals as well as in human erythrocytes. These results may explain the increase in cardiac glycoside sensitivity with age which is not accounted for by the reduction in kidney function. Furthermore, changes in both binding affinity and capacity are known to occur in several diseases which are more common in older patients. Therefore, we have measured the number and affinity of cardiac glycoside receptors in atrial samples from 209 patients and in papillary muscle samples from 59 patients taken during coronary bypass graft surgery or mitral valve replacement. Further, the maximal increase in force of contraction was measured using papillary muscle strips from some of these patients. Our results show no significant age-dependent alteration in the characteristics of the cardiac glycoside receptors but a reduced myocardial receptor density in males (3.47 +/- 0.14 X 10(14)/g protein) compared with females (4.44 +/- 0.21 X 10(14)/g protein) (p less than 0.001) which is more pronounced in older patients. About 30% fewer cardiac receptors either per g protein or per g wet weight are present in patients with coronary heart disease or dilative cardiomyopathy. The maximal inotropic effect of ouabain in human papillary muscle strips is correlated with the number of cardiac glycoside receptors present.(ABSTRACT TRUNCATED AT 250 WORDS)