Abstract
Cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. Pioglitazone (PIO) is used for the treatment of type 2 diabetes mellitus and there is some evidence that it may improve ventricular function in diabetic patients. The effects of PIO on electrical conduction in the Goto-Kakizaki (GK) type 2 diabetic rat heart have been investigated. Transmitter devices were surgically implanted in GK and control rats aged 7 months. PIO at concentrations (2.5 to 20 mg/kg) was added to the drinking water. Animals received each concentration of PIO for 2 weeks. Bodyweight and blood glucose were measured periodically. The electrocardiogram was recorded throughout the study. Blood glucose was higher in GK rats compared to controls and was progressively reduced in GK rats treated with increasing concentrations of PIO. A modest reduction in heart rate was associated with a significant increase in PQ interval in GK rats compared to controls. Heart rate and PQ interval were not additionally altered by PIO. QRS complex and QT interval were not altered in GK compared to control or by PIO. In conclusion daily oral doses of PIO in the range 2.5 to 20 mg/ kg during a period of 14 weeks appeared to have little effect on electrical conduction in GK and control rat heart.
Highlights
It is well known that the prevalence of diabetes mellitus in the United Arab Emirates is among the highest in the world and that cardiovascular complications are the major cause of morbidity and mortality in diabetic patients [1]
Blood glucose was higher in GK rats compared to controls and was progressively reduced in GK rats treated with increasing concentrations of PIO
A modest reduction in heart rate was associated with a significant increase in PQ interval in GK rats compared to controls
Summary
It is well known that the prevalence of diabetes mellitus in the United Arab Emirates is among the highest in the world and that cardiovascular complications are the major cause of morbidity and mortality in diabetic patients [1]. In addition to an increased risk of heart attack and stroke, cardiac electrical conduction abnormalities are frequently observed in diabetic patients [9,10,11]. These include various arrhythmias [9,10,11], atrioventricular block [12], prolonged QT interval and sudden death [10,11,13]. The Goto-Kakizaki (GK) rat is a well characterized experimental model of type 2 diabetes mellitus displaying a variety of characteristics that are frequently observed in type 2 diabetic patients including elevated blood glucose, insulin resistance, and disturbances in cholesterol, triglyceride, high-density and low-density lipoproteins [15,16]. Previous studies in our laboratory have demonstrated a variety of electrical conduction distu-
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