Induction of Paradoxic Bradycardia in Rats by Inferior Vena Cava Occlusion During the Administration of Isoproterenol

INTRODUCTION: Testing human susceptibility for vasodepressor reactions involves combining venous return restriction by passive upright tilting and administering isoproterenol. While sympathetic tone is usually increased by the stimuli that incite a vasodepressor reaction, it is not known if the increased sympathetic tone is an essential or passive component of the mechanism that triggers the reaction. Given that paradoxic bradycardia is a major manifestation of vasodepressor reactions and allowing for the possible extrapolation between paradoxic bradycardia in rats and vasodepressor reactions, we examined the role of sympathetic tone in the paradoxic bradycardia reaction. Paradoxic bradycardia was induced in rats by inferior vena cava occlusion during an isoproterenol infusion. To examine the role of increased sympathetic tone on this reaction, we studied whether carotid artery perfusion (80 to 100 mmHg) during inferior vena cava occlusion, a maneuver that blunts the rise in sympathetic tone, inhibits paradoxic bradycardia. METHODS AND RESULTS: The maximum changes in R-R were measured during 60 seconds of inferior vena cava occlusion as follows: (a) in control the heart rate accelerated (delta R-R - 10.2 +/- 2.3 msec, P < 0.001); (b) during an infusion of isoproterenol, paradoxic bradycardia occurred (delta R-R + 140.6 +/- 18.2 msec, P < 0.001), and this was inhibited by common carotid artery perfusion (delta R-R - 6.6 +/- 1.5 msec, P < 0.001); and (c) following carotid sinus denervation and during an infusion of isoproterenol, paradoxic bradycardia was induced without and with carotid artery perfusion (delta R-R + 122.6 +/- 12.0 msec, P < 0.001; delta R-R + 151.8 +/- 12.7 msec, P < 0.001, respectively). CONCLUSIONS: Since carotid artery perfusion during inferior vena cava occlusion inhibits paradoxic bradycardia only when the carotid sinus is innervated, we conclude that carotid artery perfusion blocks the reaction by increasing carotid sinus afferents, thereby limiting the increased sympathetic tone during inferior vena cava occlusion, and not as a result of cerebral perfusion. Thus, the paradoxic bradycardia resulting from inferior vena cava occlusion requires activation of sympathetic tone as a result of carotid sinus hypotension.