Comparative response of the developing canine myocardium to inotropic agents

Developmental changes in cardiac muscle function were assessed in isolated dog ventricular muscle strips obtained from dogs of three age groups: 2 day, 4 wk, and adult. Active tension (AT) and maximum rate of contraction and relaxation (+dT/dt, -dT/dt) increased significantly with age. Total contraction time increased with age. Time to peak tension increased between 4 wk and adulthood, and relaxation time increased between 2 day and 4 wk (P less than 0.05). The degree of post-"extra stimulus" potentiation in response to a single premature extra stimulus (SPES) or to sustained paired stimulation (SPS) was similar in all age groups. However, a longer period of SPS was necessary to reach peak AT in young animals than in adults. AT, +dT/dt, -dT/dt, and (-dT/dt)/T increased significantly in all age groups in response to increasing concentrations of isoproterenol. However, while (+dT/dt)/T increased significantly in the 4-wk and adult groups, it remained unchanged from control in the 2-day group with increasing concentration of isoproterenol. The ED50 of isoproterenol was significantly greater in the 2-day and 4-wk groups than in the adult group. AT increased significantly in young muscles but not in adult muscles when additional calcium was added to the bath containing the highest concentration of isoproterenol. In adult muscles SPS produced the greatest AT but not in the 2-day group, which required increased calcium concentration as well as isoproterenol. Maturation of several membrane systems is implicated.