Age-dependence of the chronotropic response to noradrenaline, acetylcholine and transmural stimulation in isolated rabbit atria.

The chonotropic response to noradrenaline, tyramine, acetylcholine and transmural electrical stimulation was compared in atria isolated from rabbits at different stages of developmental after birth (day 2 to day 210). Pacemaker rates understeady state conditions were related inversely to days after birth; the rate in atria from rabbits at day 2 was significantly greater than that at days 10-210. The rate of neonatal rabbit atria was not significantly reduced by propranolol and the positive chontropic response to noradrenaline was not significantly reduced by propranolol and the positive chronotropic response to noradrenaline was not significantly different in atria from ages of rabbits as far as threshold concentrations for inducing tachycardia and ED50's were concerned. The maximum rate induced by noradrenaline was higher in neonatal rabbit atria than in adult rabbit atria. The effect of tyramine was approx. the same regardless of age. Increase in the pacemaker rate induced by transmural neural stimulation varied directly with age. The negative chronotropic effect of acetylcholine was greater in neonatal than in adult rabbit atria; the ED50 in the former was significantly less than in the latter. Bradycardia induced by transmural stimulation of intracardiac cholinergic nerves was related directly to age. Tachycardia in the neonatal rabbit atria may be due to electrogenic characteristics of pacemaker cells which differ from those in adult rabbit atria. Our evidence strongly suggests that the adrenergic and cholinergic nerves innervating the S-A node develop at an early postnatal stage in the rabbit.