Accentuated Antagonism in Cold Induced Sympathetic Activation

Title: Accentuated Antagonism in Cold Induced Sympathetic Activation Introduction: Accentuated antagonism (AA) is a physiological phenomenon where sympathetic nerve activity (SNA) potentiates the action of the vagus nerve on heart rate slowing. This concept has been thoroughly investigated in animals but has not sufficiently been studied in humans. Exploring AA has significant public health relevance because in states when SNA is high, any given activation of the vagus may slow heart rate to a dangerous degree. Therefore, giving cardio-selective sympathetic blocking agents may have significant clinical utility in these settings. Hence, we hypothesize that R-R interval (RRI) will be higher when background SNA is high during 4 degree Celsius cold pressor test (CPT) compared to a room temperature control, and that this difference will be mitigated by giving intravenous metoprolol. Methods 4 healthy human subjects were recruited and informed consent was obtained according to the Declaration of Helsinki. Subjects first underwent baseline -60 mm Hg neck suctions to stimulate vagal nerve-mediated heart rate slowing through the baroreflex. These suctions were repeated after submersion of the hand at wrist level in 4°C water and then 23°C water. These conditions were repeated with infusion of 10 mL saline placebo and up to 10 mg of intravenous metoprolol. We were able to differentiate between the vagal and sympathetic effects on the heart by either infusing saline or blocking the SNA with metoprolol at both temperatures. Results: In comparison of the placebo group with the Metoprolol group in 25°C water, we did not see a significant different in the RR interval (Difference of Means=58.007 milliseconds; P=0.344). In addition we did not see a statistical difference when comparing the RR interval of the placebo group with the Metoprolol group in 4°C water (Difference of Means=72.073 milliseconds; P=0.247). However, there are significant trends within the data that deserve further study. Conclusions: We believe the lack in statistical significance of the data presented is due to the small number of participants in the study. This study warrants further elucidation of the concept of accentuated antagonism in human subjects.