AGE-DEPENDENT REDUCTION OF THE RESPONSE OF RAT CARDIAC-MUSCLE TO THE PHOSPHODIESTERASE INHIBITOR MILRINONE

This study aimed to investigate whether milrinone effect on cardiac mu scle contractility undergoes to age-related changes. Experiments were carried out on papillary muscles isolated from right ventricle of Brow n Norway rats belonging to two different age groups : 2 month old and 18 month old. The effect of milrinone (10-100 mu M) on rat cardiac mus cle in vitro preparations was characterized by a reduction of peak dev eloped tension and of contraction duration. Furthermore, the recovery of contractility after a contractile cycle, i.e. the mechanical restit ution was faster in the presence of milrinone than in control conditio ns. All these effects were reduced in preparations from 18 month old r ats compared to preparations from 2 month old rats. The decrease of mi lrinone effect on the mechanical restitution was particularly pronounc ed. The reduction of the milrinone effects is likely connected with th e reduction of the maximal effect of adrenergic stimulation, although the molecular basis of this link is not yet clearly understood.