Search

Vasodepressor reactions, characterized by paradoxic bradycardia, were induced in rats when the inferior vena cava was occluded during an infusion of isoproterenol. The effects of alpha-adrenergic receptors and their interaction with beta-adrenergic receptors on the vasodepressor reaction were examined. Inferior vena cava occlusion was performed for 60 s, and the maximum changes in R-R were measured in 44 rats: (i) in control conditions, during phenylephrine (alpha 1-adrenergic agonist), and during a combined infusion of phenylephrine and isoproterenol the R-R shortened significantly (-16.8 +/- 1.4, -24.1 +/- 2.2, and -4.9 +/- 1.2 ms, respectively); (ii) isoproterenol and phentolamine and prazosin (nonselective and selective alpha-adrenergic antagonists) prolonged the R-R paradoxically (+89.2 +/- 9.5, +58.9 +/- 4.1, and +64.4 +/- 10.2 ms, respectively); (iii) atropine and right vagotomy did not affect the phentolamine-induced R-R prolongation (+66.0 +/- 2.4 and +73.8 +/- 13.7 ms, respectively), but it was blocked by left vagotomy (-9.6 +/- 1.1 ms); (iv) propranolol inhibited the prazosin-induced R-R prolongation (-14.3 +/- 2.8 ms,); (v) epinephrine (alpha- and beta-adrenergic agonist) shortened the R-R interval (-9.5 +/- 2.2 ms), but following prazosin, epinephrine induced R-R prolongation (+13.7 +/- 6.0 ms,); (vi) norepinephrine induced R-R prolongation (+21.0 +/- 6.7 ms). It was concluded that (i) paradoxic bradycardia (vasodepressor reaction) dependent on vagal afferents can be induced by reduced venous return in the presence of excess exogenous beta 1-adrenergic stimulation (isoproterenol) or when endogenous alpha-adrenergic tone is antagonized (phentolamine or prazosin); (ii) the reaction can be blocked by alpha 1-adrenergic stimulation; and (iii) epinephrine does not induce paradoxic bradycardia, whereas norepinephrine does, and this may be due to the stronger alpha-stimulating properties of epinephrine.

Vasodepressor reactions were induced in 27 rats by a combination of inferior vena caval occlusion and an infusion of isoproterenol. A vasodepressor reaction was defined as paradoxical heart rate slowing during inferior vena caval occlusion. The R-R intervals were measured at 5-s intervals before, during, and after 60 s of inferior vena caval occlusion. The purpose of this study was to examine the role of the right and left vagus nerve and the right and left stellate ganglia in this reflex. Under control conditions inferior vena caval occlusion accelerated the rate (R-R, -15.9 +/- 0.9 ms). During an infusion of isoproterenol (0.5-1.0 micrograms.min-1), inferior vena caval occlusion produced paradoxical rate slowing, i.e., a vasodepressor reaction (R-R, +75.0 +/- 2.2 ms). The vasodepressor reaction was examined during inferior vena caval occlusion and isoproterenol under the following additional states: atropine methyl bromide or right vagotomy did not alter the reaction; left vagotomy eliminated the reaction; and right or left stellectomy greatly reduced the vasodepressor reaction. We conclude the following: (1) left vagal afferents mediate the vasodepressor reaction; (2) cardiac sympathetic fibers participate in the vasodepressor reaction by withdrawing efferent tone through the right stellate ganglion, and by generating the afferent signal, which triggers the vasodepressor reaction through the left stellate ganglion.

Ventricular tachycardia or ventricular fibrillation was electrically induced in 38 normal rats (group 1) and 24 sympathetically denervated rats (6-hydroxydopamine) (group 2). The time for spontaneous reversion to sinus rhythm was measured during (1) control, (2) isoproterenol, and (3) the combination of isoproterenol and phenylephrine. The time for spontaneous reversion was the same in both groups in the three states. The reversion time was prolonged threefold by isoproterenol, and restored to control values when phenylephrine was added to the infusion of isoproterenol. The tachycardia duration and the refractory period were inversely related: log10 (tachycardia duration) = 3.466-0.091 (refractory period). Ventricular tachycardia/fibrillation induction was examined as follows: (i) Ventricular tachycardia/fibrillation was induced in 100% of normal rats (group 1), but only 42% of the denervated rats (group 2, p less than 0.001); (ii) during isoproterenol, ventricular tachycardia/fibrillation was induced in 100% of rats of both groups; and (iii) when phenylephrine was added to isoproterenol, ventricular tachycardia/fibrillation was induced in 100% of group 1 rats versus 82% of group 2 rats, (p = NS). These observations suggest (1) the induction of ventricular tachycardia/fibrillation is highly dependent on intact sympathetic innervation, and (2) exogenous adrenergic agonists modulate the duration of ventricular fibrillation through their effects on ventricular refractory period, independent of sympathetic innervation.

Unlabelled: Testing for the susceptibility for vasodepressor reaction in humans involves the combination of restriction of venous return by passive upright tilting and the administration of isoproterenol. To explore the basis of the vasodepressor test in humans, the present experiment examined whether a reduced cardiac volume coupled with adrenergic stimulation causes a vasodepressor reaction in rats. Vasodepressor reaction was defined as paradoxical heart rate slowing in conjunction with hypotension during inferior vena caval occlusion. Inferior vena caval occlusion was performed for 60 s and the maximum changes in R-R were measured during seven states as follows. (A) Under control conditions inferior vena caval occlusion alone accelerated the rate in 32 of 32 rats (delta R-R, -13.9 +/- 1.7 ms, p less than 0.001). (B) When inferior vena caval occlusion was performed during an infusion of isoproterenol (0.5-1.0 micrograms.min-1), a vasodepressor reaction was observed in all rats as the heart rate slowed (delta R-R, +138.1 +/- 14.8 ms, p less than 0.001). The vasodepressor reaction was further examined during isoproterenol and inferior vena caval occlusion under five additional states. (C) After atropine the vasodepressor reaction was unchanged (delta R-R, +132.7 +/- 24.8 ms, p less than 0.001). (D) After bilateral vagotomy the paradoxical slowing was eliminated. (E) After intrapericardial lidocaine the paradoxic slowing was eliminated. (F) After bilateral stellectomy nonsignificant slowing was still present, but this was markedly reduced when compared with B (p less than 0.001). (G) Following chronic chemical sympathetic denervation with 6-hydroxydopamine the paradoxic bradycardia was eliminated., Conclusions: (1) Reduced cardiac volume combined with adrenergic stimulation can stimulate a vasodepressor reaction; (2) the vasodepressor reaction requires signalling by the afferent but not efferent vagal fibers; (3) the bradycardia is mainly due to withdrawal of sympathetic efferent tone.

Parasympathetic neural activity modulates some ventricular arrhythmias in man. Therefore, a canine model of arrhythmias produced by the interaction of halothane and catecholamines was used to study the effects of vagal stimulation on the induction of ventricular fibrillation. The dose of catecholamine required to induce ventricular fibrillation was determined during a constant heart rate. Vagal stimulation reversibly raised the norepinephrine dose that produced ventricular fibrillation from 16.4 +/- 2.4 to 30.0 +/- 3.8 micrograms (p less than 0.001, n = 10), and the epinephrine dose from 15.5 +/- 2.0 to 22.5 +/- 2.6 micrograms (p less than 0.001, n = 5). Following atropine, vagal stimulation failed to raise the threshold dose of norepinephrine (16.8 +/- 2.4 vs. 18.3 +/- 3.3 micrograms, nonsignificant, n = 6) or epinephrine (15.5 +/- 2.0 vs. 16.0 +/- 2.3 micrograms, nonsignificant, n = 5). Ligation of the cervical vagus nerves did not affect the epinephrine threshold dose (16.3 +/- 3.3 vs. 17.5 +/- 2.7 micrograms, nonsignificant, n = 5). Following elevation of basal vagal tone by morphine premedication, the norepinephrine threshold of 53.0 +/- 9.2 micrograms declined by a nonsignificant amount to 46.5 +/- 11.5 micrograms after vagotomy (nonsignificant, n = 5). Thus resting vagal tone does not prevent catecholamine-halothane-induced ventricular fibrillation, whereas increasing vagal tone by electrical stimulation substantially protects against this arrhythmia. The protection is mediated through a muscarinic cholinergic receptor.

Three methods of inducing focal conduction disturbances in free-running sheep Purkinje fibers (symmetric and asymmetric focal cooling and asymmetric focal crushing) were explored in 50 preparations. Complete unidirectional block was induced in only a minority of symmetrically cooled preparations whereas the asymmetric lesions generated this conduction disturbance in 80-85% of preparations. The block was more stable when induced by crushing than by asymmetric cooling but was more readily reversible with the latter. The direction of block coincided with the least abrupt gradient in the intensity of the lesion (82-94%), was reversible upon reorientation of the cooling lesion, and was independent of anatomic orientation or pre-existing asymmetries of conduction. The models of unidirectional block described in this paper may be useful in the elucidation of the mechanism of asymmetric conduction disturbances and in studies of the mechanism of action of antiarrhythmic drugs.