In vivo demonstration of maturational changes of the chronotropic response to α-adrenergic stimulation

In vitro studies suggest that neonates and adults may have different cardiac chronotropic responses to α-adrenergic stimulation. To investigate these differences in vivo, three groups of dogs were studied. Group I = 12 puppies, ages 3-7 days; group II = 12 puppies ages 8-15 days, and group III = seven adult dogs. Heart rate and blood pressure determinations were made in the control setting and then after combined β-adrenergic and parasympathetic blockade (propranolol 0.6 mg/kg and bilateral vagotomies). Alpha-stimulation was then achieved with phenylephrine given in doses of 0.5, 1.0, and 10.0 μg/kg/min. A second, high dose of propranolol (1.0 mg/kg intravenously) was administered after the highest phenylephrine infusion dosage to assure complete β-blockade. Finally, α-blockade was achieved with phentolamine (groups I and II: 0.5 mg intravenously; group III: 5.0 mg intravenously). An α-mediated positive chronotropic effect was observed in 42 and 100% of subjects in groups I and II, respectively, but never observed in the adults. Whereas α-blockade with phentolamine resulted in a large decrease in heart rate of all puppies (groups I and II), it had no effect on adults. Blood pressure responses were similar in all three groups. Thus, there are important maturational changes in the chronotropic response to α-adrenergic stimulation and blockade demonstrable in the intact neonatal canine.