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Divergent cardiac effects of the first and second generation hypoglycemic sulfonylurea compounds
G Ballagi-Pordány1, A Köszeghy, M Z Koltai
1National Institute of Cardiology, Research Department, Budapest, Hungary.
Abstract:
The effects of first and second generation hypoglycemic sulfonylureas on the incidence of ventricular ectopic beats and on the duration of transitional ventricular fibrillation in the ischemic rat heart were investigated. First generation sulfonylurea compounds (tolbutamide, carbutamide and gliclazide) in 105 preparations increased, while second generation sulfonylurea compounds (glibenclamide and glipizide) in 50 preparations decreased in a dose-dependent manner both the number of ventricular ectopic beats and the duration of transitional ventricular fibrillation during the first 30 min after ligation of the left anterior descending coronary artery. Therefore, second generation sulfonylureas should be preferred in the treatment of type 2 diabetics with ischemic heart diseases, if satisfactory metabolic control cannot be achieved by a treatment regimen and diet alone.
Insights
Second-generation sulfonylureas reduce ventricular arrhythmias in ischemic rat hearts, unlike first-generation drugs. This suggests they are preferable for type 2 diabetics with heart disease when diet alone is insufficient.
Area of Science:
- Cardiology
- Pharmacology
- Endocrinology
Background:
- Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular complications, including ischemic heart disease.
- Sulfonylureas are commonly prescribed oral hypoglycemic agents for T2DM management.
- The impact of different sulfonylurea generations on cardiac electrophysiology during ischemia requires further clarification.
Purpose of the Study:
- To investigate the differential effects of first-generation and second-generation sulfonylureas on cardiac electrophysiological parameters during myocardial ischemia.
- To assess the influence of these agents on ventricular ectopic beats and ventricular fibrillation duration in an ischemic rat heart model.
Main Methods:
- The study utilized an in vivo rat model of myocardial ischemia induced by ligation of the left anterior descending coronary artery.
- Ventricular ectopic beats and the duration of transitional ventricular fibrillation were measured following drug administration.
- First-generation (tolbutamide, carbutamide, gliclazide) and second-generation (glibenclamide, glipizide) sulfonylureas were administered in a dose-dependent manner.
Main Results:
- First-generation sulfonylureas significantly increased the incidence of ventricular ectopic beats and prolonged ventricular fibrillation duration.
- Second-generation sulfonylureas demonstrated a dose-dependent reduction in both ventricular ectopic beats and ventricular fibrillation duration.
- These effects were observed during the initial 30 minutes following coronary artery ligation.
Conclusions:
- Second-generation sulfonylureas exhibit cardioprotective electrophysiological effects during myocardial ischemia, contrasting with first-generation agents.
- The findings suggest that second-generation sulfonylureas may be a preferred therapeutic option for type 2 diabetic patients with ischemic heart disease, particularly when glycemic control is challenging with diet and exercise alone.