Beneficial Effects of Magnesium Treatment on Heart Rate Variability and Cardiac Ventricular Function in Diabetic Rats

Abstract

Background: Diabetes mellitus induces life-threatening cardiovascular complications such as cardiac autonomic neuropathy and ventricular dysfunction and is associated with hypomagnesemia. In this study, we investigated the short-term effects of magnesium (Mg2+) treatment on streptozotocin (STZ)-induced diabetic cardiac complications. Methods: Adult Wistar rats were treated once with STZ (50 mg/kg, intraperitoneally [ip]) or vehicle (citrate) and then daily for 7 days with MgSO4 (270 mg/kg, ip) or saline. On the eighth day, in vivo tail-pulse plethysmography was recorded for heart rate variability (HRV) analysis, and ex vivo Langendorff-based left ventricular (LV) pressure–volume parameters were measured using an intraventricular balloon. Measurements of plasma lipid and Mg2+ levels as well as blood glucose and cardiac tissue Mg2+ levels were also performed. Results: Treatment with Mg2+ prevented diabetes-induced alterations in the standard deviation of the averages of normal-to-normal (NN) intervals (SDANN), root mean square differences of successive NN intervals (RMSSD), heart rate, and low-frequency (LF) power–high-frequency (HF) power ratio. In addition, Mg2+ restored orthostatic stress-induced changes in SDANN, RMSSD, and LF–HF ratio in diabetic rats. In isolated hearts, Mg2+ reversed the diabetes-induced decrease in LV end-diastolic elastance and the right shift of end-diastolic equilibrium volume intercept, without altering LV-developed pressure or end-systolic elastance. However, Mg2+ did not prevent the elevation in blood glucose, total cholesterol, and triglycerides or the decrease in high-density lipoprotein cholesterol in diabetes. Plasma- or cardiac tissue Mg2+ was not different among the treatment groups. Conclusion: These results suggest that Mg2+ treatment may attenuate diabetes-induced reduction in HRV and improve LV diastolic distensibility, without preventing hyperglycemia and dyslipidemia. Thus, Mg2+ may have a modulatory role in the early stages of diabetic cardiovascular complications.