Severe hypoglycemia causes fatal cardiac arrhythmias. The extent to which the parasympathetic nervous system regulates hypoglycemia-induced fatal arrhythmias remains unknown. To investigate the role of vagal innervation in regulating arrhythmias during severe hypoglycemia, Sprague Dawley rats underwent vagotomy (left vagus nerve transection adjacent to the carotid artery; n = 15) or sham surgery (control; n = 13). One week after surgery, all rats underwent hyperinsulinemic (0.2 U/kg/min) severe hypoglycemic (10-15 mg/dl) clamps with electrocardiogram recordings. Rats with vagotomy had increased heart rate at baseline and throughout the clamp, indicating successful vagotomy. Glucose infusion rates during hypoglycemia were increased 1.7-fold in rats with vagotomy, but epinephrine values were similar between the groups. Vagotomy resulted in fewer cardiac arrhythmias including a 12-fold decrease in 2nd degree heart block. Reduction in arrhythmias was associated with a 7-fold decrease in severe hypoglycemia-induced mortality in rats with vagotomy (7%) compared to controls (46%).
In summary, vagal transection reduces mortality and cardiac arrhythmias during severe hypoglycemia. Since vagal innervation mediates severe hypoglycemia-induced sudden death, targeting the parasympathetic nervous system may be a logical approach to prevent sudden death for at-risk people with insulin treated diabetes.
C.M. Reno: None. A.J. Skinner: None. J. Bayles: None. S.J. Fisher: None.