ROLE OF AGING ON ELECTRICAL, MECHANICAL, AND CORONARY MODIFICATIONS INDUCED BY OUABAIN AND EPININE IN ISOLATED RAT-HEART

Objective: The contractile response to digitalis and beta adrenoceptor agonists is lower in the senescent than in the adult myocardium, whil e the development of ventricular arrhythmias is increased. The aim of this study was to examine the effects of aging on cardiac response to digitalis and an adrenergic agonist used clinically. Methods: The elec trical and mechanical responses were tested in isolated and perfused h earts from 3-24 month old rats receiving 15 min infusion of digitalis drug (ouabain, 6 X 10(-5) M) alone, and after 5 min of beta adrenocept or agonist drug (epinine, 1.5 X 10(-7) M). Results: Ouabain action was associated with a rise in left ventricular end diastolic pressure (p < 0.01) which increased progressively with aging, and with an elevatio n of left ventricular developed pressure (p < 0.01) which decreased pr ogressively with aging. Epinine induced a reduction of left ventricula r end diastolic pressure (p < 0.01) and a rise in left ventricular dev eloped pressure (p < 0.01) but both effects decreased progressively wi th aging. Ouabain reduced coronary flow and this decrease was more pro nounced with aging (p < 0.01), while epinine caused an increase (p < 0 .01) that diminished in older hearts. Ouabain given after epinine resu lted in a greater increase in left ventricular end diastolic pressure than epinine (p < 0.01) but lower than that caused by ouabain alone (p < 0.01), a greater increase in left ventricular developed pressure th an epinine and ouabain (p < 0.01), and a smaller reduction of coronary flow rate than ouabain alone (p < 0.01). All these effects, however, diminished progressively with aging. Arrhythmia scores were higher dur ing ouabain than in control (p < 0.01) and in epinine treated hearts ( p < 0.01); pretreatment with epinine did not modify arrhythmia score d uring ouabain administration. The number and severity of arrhythmias, however, increased with aging in all groups. Conclusions: Aging has a negative effect on both the positive inotropic and the arrhythmogenic effects of ouabain and epinine, although these phenomena are more pron ounced during ouabain administration. However, when the two drugs are given simultaneously, epinine does not modify the arrhythmogenic effec t of ouabain but reduces some of its deleterious haemodynamic effects.