A hemodynamic excitatory response to veratridine in the in utero lamb

The inhibitory hemodynamic effects of the Bezold-Jarisch reflex in the adult animal, which play a role in the response to disease states, are elicited by veratridine and are mediated by vagal afferents. We tested whether the reported excitatory response to veratridine in the fetal animal may be caused by a maturational phase in the Bezold-Jarisch response. The effects of proprananol and atropine on the hemodynamic response to veratridine were examined at 124-141 d (mean, 133 d) of gestation in 11 fetal lambs instrumented long-term (instrumentation, 111-129 d of gestation). Seven lambs had intact vagal nerves, and four had bilateral cervical vagotomies. Veratridine injected into the superior vena cava (0.3 to 2.8 micrograms/kg) and the left atrium (0.2 to 0.8 microgram/kg) increased heart rate, arterial pressure, and left ventricular output, with the responses to left atrial injections occurring more rapidly. Propranolol markedly inhibited the increase in arterial pressure; atropine had no effect. Neither carbocaine, perfused around the cervical vagi, nor bilateral transection of the vagal nerves altered the hemodynamic excitatory response to veratridine. These findings demonstrate that the fetal excitatory response to veratridine is not mediated by vagal afferents, indicating the Bezold-Jarisch reflex does not undergo a maturational change from an excitatory reflex to an inhibitory one and suggesting the maturational loss of a sympathetically mediated hemodynamic reflex.