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 muscle contractility undergoes to age-related changes. Experiments were carried out on papillary muscles isolated from right ventricle of Brown Norway rats belonging to two different age groups: 2 month old and 18 month old. The effect of milrinone (10-100 microM) on rat cardiac muscle in vitro preparations was characterized by a reduction of peak developed tension and of contraction duration. Furthermore, the recovery of contractility after a contractile cycle, i.e. the mechanical restitution was faster in the presence of milrinone than in control conditions. All these effects were reduced in preparations from 18 month old rats compared to preparations from 2 month old rats. The decrease of milrinone effect on the mechanical restitution was particularly pronounced. The reduction of the milrinone effects is likely connected with the reduction of the maximal effect of adrenergic stimulation, although the molecular basis of this link is not yet clearly understood.