ABSTRACT-The influence of 5-min global cerebral ischemia on the facilitatory modulation of the vagal baroreflex through central a2-adrenoceptors or by the electrical stimulation of the septum was investigated in anesthetized dogs. Reflex bradycardia was produced by a bolus injection of phenylephrine at a dose which produces about a 25-mmHg increase in mean blood pressure. The ischemia was produced by the oc clusion of the brachiocephalic and the left subclavian arteries with preceding ligation of the intercostal arteries. Clonidine at 10 pg, administered intracisternally, decreased the blood pressure and heart rate and facilitated the vagal reflex bradycardia. During the reperfusion period following ischemia, however, clonidine failed to affect the reflex bradycardia. Electrical stimulation of the septal region facilitated the reflex bradycardia without marked influences on the basal blood pressure and heart rate. The facilitatory effect was dependent on the frequency (10 to 75 Hz) and amplitude (3 to 15 V) of stimulation and was not observed after vagotomy or ischemic insult. These results suggest that 5-min global cerebral ischemia may produce the dysfunction of the neurons which are closely related to the baroreflex loop and receive the facilitatory modulation through a2-adrenoceptors and/or from the forebrain structures, leading to the dysfunction of the vagal baroreflex.Keywords: Ischemia (cerebral), Baroreflex (vagal), a2-Adrenoceptor, Septum Global cerebral ischemia of 5 min produces a selective dysfunction of the vagal component of the baroreflex in dogs (1). Since the pretreatments with a2-adrenoceptor blocking agents (2), but not MK-801 (3), a non-competi tive N-methyl-D-aspartate (NMDA) antagonist, provided cerebral protection in this experimental model, it could be speculated that a2-adrenoceptors, but not NMDA recep tors, might play a pathogenetical role. On the other hand, stimulation of the central a2-adrenoceptors has been shown to facilitate the vagal baroreflex (4-6). Thus, one of the hypotheses was that excessive activation of a2 adrenoceptors during ischemia and the early reperfusion period might alter the a2-adrenergic system, or injure the neurons with a2-adrenoceptors, leading to the dysfunction of neuronal networks that are essential to the vagal baroreflex and/or its modulatory systems.In this context, we investigated firstly the influence of 5 min global cerebral ischemia on the effects of intracister nally administered clonidine to confirm the post-ischemic dysfunction of the central a2-adrenergic systems. Second ly, we attempted to investigate further the influence of ischemia on another neurogenic modulation of the baroreflex. For this purpose, we performed the electrical stimulation of the forebrain structure within the septum, which has been shown to selectively facilitate the vagal component of the baroreflex (7).
MATERIALS AND METHODS
AnimalsForty-eight mongrel dogs of either sex weighing 8 to 19 kg were anesthetized with sodium pentobarbital at 32 mg/kg, i.v., followed by an inf...