Response of the neonatal heart to a new inotropic agent, RO2-2985 (X537A).
The ionophore RO2-2985 did not produce a positive inotropic response in 1-day-old canine isolated ventricle. A gradual increase in inotropic response was seen with age. Isolated atria, however, exhibited a positive inotropic response at birth (50% increased dF/dt), which became progressively greater with age (100% increase in dF/dt at 15 days of age). In the neonatal heart in situ there was a positive inotropic response in 1-day-old puppies (40% increase in left ventricular dF/dt) with progressively greater responses with age (135% increase in left ventricular dF/dt at 11 days of age). There was a positive chronotropic (75-125% increase) response to RO2-2985 at all ages studied. The drug elevated systemic arterial pressure (150% increase in mean arterial pressure) to a similar degree in all ages studied. RO2-2985 depressed total calcium binding by both neonatal and adult isolated cardiac sarcoplasmic reticulum approximately 50%.
D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002264:Carboxylic Acids / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D007476:Ionophores / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D014439:Tyramine / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002264:Carboxylic Acids; D007476:Ionophores; D002118:Calcium; D014439:Tyramine