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Low and High Doses of Glibenclamide
Increase the Risk of Reperfusion-Induced
Arrhythmias in a Conscious Diabetic
Sheep Model

del Valle, Héctor F.; Negroni,
Jorge A.; Lascano, Elena C.

Department of Physiology, Pharmacology and Biochemistry,
Favaloro University, Buenos Aires, Argentina

Introduction: There are controversial findings regarding the sulfonylurea action on myocardial arrhythmias. Many works have mentioned them (with special emphasis about glibenclamide) as an antiarrhythmic drugs in the setting of ischemia and reperfusion in experimental models and perhaps in patients. However, other authors have found glibenclamide-induced arrhtyhmias and glibenclamide-worsening effects on myocardial recovery from stunning. The absence of studies in diabetic animal models is of particular interest.

Objective: The purpose was to assess whether glibenclamide (G) have an effect in malignant arrhythmia appearance in a conscious alloxan-induced (1gr total dose) diabetic sheep model.

Methods: The animals were instrumented with a pneumatic cuff occluder positioned at the distal third portion of the anterior descending coronary artery and a pair of steel multifilament wires sutured to the right ventricular surface for electrocardiographic recordings. Three groups of sheep were studied: a) control diabetic (C, n=7) = 12 min ischemia (I) followed by 10 min reperfusion (R), b) diabetic sheep plus glibenclamide 0.1 mg/Kg (G 0,1, n=6) and c) diabetic sheep plus glibenclamide 0.4 mg/Kg (G 0,4, n=6). In the last two groups the drug was infused 30 min before I-R. Arrhythmias were classified according to the Lambeth convention and an assessment of their severity was performed by using the Bernauer's arrhythmia severity index (ASI).

Results: Glibenclamide infusion resulted in a high incidence of reperfusion-induced arrhythmias as the following table shows: Table 1

Conclusion: Glibenclamide resulted in a high proarrhythmic intervention during reperfusion. This result would explain the reported elevated mortality rate in diabetic patients treated with oral hypoglycemic agents after an acute cardiovascular event.



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2nd Virtual Congress of Cardiology

Dr. Florencio Garófalo
Steering Committee
Dr. Raúl Bretal
Scientific Committee
Dr. Armando Pacher
Technical Committee - CETIFAC

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