The Prophylactic Effects of Metoprolol, Diltiazem, and Pilocarpine on Hypoglycemia-Induced Prolongation of QT Interval

Abstract

Background Insulin-induced hypoglycemia has been demonstrated to prolong the corrected QT (QTc) interval. Prolongation of the QTc interval, especially in diabetic patients using insulin, can cause fatal ventricular arrhythmias. The aim of this study was to evaluate the effects of metoprolol, diltiazem, and pilocarpine on hypoglycemia-induced QTc prolongation. Methods Thirty male rats were randomly distributed into the following five groups: Group 1 (1 mL/kg saline, n=6), Group 2 (40 U/kg crystalline insulin + saline, n=6), Group 3 (40 U/kg crystalline insulin + 1 mg/kg metoprolol, n=6), Group 4 (40 U/kg crystalline insulin + 0.8 mg/kg pilocarpine, n=6), and Group 5 (40 U/kg crystalline insulin + 2 mg/kg diltiazem, n=6). Three hours after insulin injection, the blood glucose level was measured in all groups. Blood glucose <40 mg/dl was defined as hypoglycemia. Electrocardiograms (ECG) were taken in lead I (DI), and QTc was calculated by using Bazett's formula. Results Group 2 (insulin + saline) showed that it had a significantly prolonged QTc interval as compared to the control group (p<0.0001). However, treatments of the rats with metoprolol, pilocarpine, and diltiazem significantly prevented prolongation of the QTc interval as compared to the insulin + saline group (p<0.005, p<0.005, and p<0.01, respectively). Conclusion The findings of the present study demonstrated the efficacy of metoprolol, pilocarpine, and diltiazem in the prevention of hypoglycemia-induced QTc prolongation in male rats.