Severe hypoglycemia can lead to fatal cardiac arrhythmias, specifically 3rd degree heart block. During hypoglycemia, the brain senses low glucose and activates the sympathetic nervous system leading to epinephrine and norepinephrine secretion. It is hypothesized that norepinephrine increases severe hypoglycemia induced fatal cardiac arrhythmias. To test this hypothesis, nondiabetic Sprague Dawley rats underwent hyperinsulinemic/severe hypoglycemic (10-15 mg/dl) clamps for 3 hours with continuous electrocardiogram recording. Rats were continuously infused with either 1) brain norepinephrine (ICV; n =15), 2) brain control (ICV aCSF; n = 11), 3) IV norepinephrine nerve terminal blocker (reserpine; n = 7), or 4) IV control (DMSO/saline; n = 6). Severe hypoglycemia induced mortality was increased to 40% with brain norepinephrine infusion compared to 27% in aCSF. Similarly, heart block was increased to 40% with brain norepinephrine infusion compared to 25% in aCSF (p < 0.05). Blockade of norepinephrine completely prevented mortality and heart block during severe hypoglycemia compared to 17% and 25% (p < 0.05), respectively, in controls.

In summary, norepinephrine increases while blockade of norepinephrine prevents fatal heart block during severe hypoglycemia. Drugs that target norepinephrine action may have therapeutic potential in people with diabetes at risk for severe hypoglycemia.

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Disclosure

E.H. Nuibe: None. M. Chambers: None. C.M. Reno-Bernstein: None.

Funding

National Institutes of Health (1R56HL160835-01); University of Utah

© 2023 by the American Diabetes Association
2023
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