A characteristic of the maturing cardiovascular system is that the maximum contractile responses of cardiac and vascular muscles increase. This increase may result from one or more of the following: a change in the tissue content of actin and myosin; an increase in the availability and/or effectiveness of calcium; or an increase in the supply of ATP or alteration in its usage. Our proposal is designed to determine the role of each of these in ventricular muscle, aortic, carotid and femoral arteries, and femoral veins from immature (5 days; 3-4 weeks) and adult dogs. Specifically, the contractility of in vitro muscle preparations will be correlated with: 1) The tissue content of actin, myosin, collagen and elastin. This will allow a more precise determination of the force generating ability of the contractile units. 2) The metabolic properties determined by simultaneously measuring O2, consumption lactate production and force development in the presence of various substrates and metabolic inhibitors. This will indicate whether the substrate requirements of these tissues change during maturation thereby contributing to altered contractility. 3) The mechanical response of intact muscles to specific probes of excitation-contraction coupling and the response of in situ chemically skinned muscles. This will enable determining the availability and effectiveness of calcium for activation of the myofilaments. Many cardiovascular drugs exert different effects in newborn compared to adult. Our long term goal is to understand the complex mechanisms operative to produce these differences so that imprved drugs and therapy may be implemented
