Severe Hypoglycemia Induced Fatal Cardiac Arrhythmias are Mediated By the Parasympathetic Nervous System In Rats复制标题

严重低血糖诱导的致死性心律失常是由大鼠副交感神经系统介导的。

The contribution of the sympathetic (SNS) versus parasympathetic (PSNS) nervous system in mediating fatal cardiac arrhythmias during insulin-induced severe hypoglycemia is not well understood. Therefore, experimental protocols were performed in non-diabetic, Sprague Dawley rats to test SNS with 1) adrenal demedullation and 2) chemical sympathectomy, and to test PSNS with 3) surgical vagotomy, 4) nicotinic receptor (mecamylamine) and muscarinic receptor (AQ-RA 741) blockade, and 5) heart perfusions with normal or low glucose, acetylcholine and/or mecamylamine. In protocols 1-4, 3-hour hyperinsulinemic (0.2U·kg·min)-hypoglycemic (10-15 mg/dl) clamps were performed. Adrenal demedullation and chemical sympathectomy had no effect on mortality or arrhythmias during severe hypoglycemia compared to controls. Vagotomy led to a 6.9-fold decrease in mortality, reduced 1 and 2 degree heart block 4.6- and 4-fold, respectively, and prevented 3 degree heart block compared to controls. Pharmacological blockade of nicotinic receptors, but not muscarinic receptors, prevented heart block and mortality versus controls. heart perfusions demonstrated that neither low glucose nor acetylcholine alone caused arrhythmias, but their combination induced heart block that could be abrogated by nicotinic receptor blockade. Taken together, acetylcholine activation of nicotinic receptors via the vagus nerve is the primary mediator of severe hypoglycemia-induced fatal cardiac arrhythmias.

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