Hypoglycemia-induced electrocardiogram changes in a rodent model of type 1 diabetes

Retrospective data was obtained from studies conducted by Reno et al. Adult male Sprague-Dawley rats (weight, 250–300 g; Charles River Laboratories, Malvern, PA) were housed individually in temperature- and light-controlled environments and fed ad libitum a standard chow diet and water. Rats underwent surgery for carotid artery and jugular vein cannulation as previously described. ECG leads were also placed subcutaneously during surgery. One wire was placed over the lower left rib cage and one was placed over the right supraclavicular fossa. A reference wire was placed over the back. Two days after cannulation, one set of rats received intraperitoneal injections of streptozotocin (65 mg/kg; Sigma, St. Louis, MO) to induce diabetes (n = 37). A second group of rats received sodium citrate buffer and acted as a control, non-diabetic group (n = 54). Blood glucose was measured from the tail vein with a glucometer (Ascensia Contour; Bayer HealthCare, Mishawaka, IN) to ensure diabetes. Rats were diabetic for two weeks prior to the hypoglycemic clamp. Overnight fasted, awake, unrestrained non-diabetic and diabetic rats underwent hyperinsulinemic (0.2 units ⋅ kg−1 ⋅ min−1; Humulin R), severe hypoglycemic (10–15 mg/dL) single step clamps with continuous ECGs for 3 hours, as previously described  ECGs were recorded every millisecond (ms) using PowerLab 26T software (LabChart; ADInstruments, Colorado Springs, CO). Arterial blood was used to determine glucose levels during the clamp with a glucometer (Ascensia Contour BG monitors; Bayer Healthcare Mishawaka, IN) every 15-minutes.

Reno CM, Daphna-Iken D, Chen YS, VanderWeele J, Jethi K, Fisher SJ. Severe hypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoadrenal activation. Diabetes. 2013;62(10):3570-81.

Reno CM, VanderWeele J, Bayles J, Litvin M, Skinner A, Jordan A, et al. Severe Hypoglycemia-Induced Fatal Cardiac Arrhythmias Are Augmented by Diabetes and Attenuated by Recurrent Hypoglycemia. Diabetes. 2017;66(12):3091-7.