Effects of metformin on QT and QTc interval dispersion of diabetic rats.
BACKGROUND
Several drugs can cause prolonged QT interval, as well as prolonged QT dispersion (QTd) in electrocardiographic (EKG) recordings. QTd may be a potentially sensitive marker of increased risk of cardiac arrhythmias and sudden cardiac death. Metformin is an effective antihyperglycemic agent used in the treatment of diabetes. However, studies have correlated dose-dependent effects of metformin on glycemia and cardiovascular risk markers.


OBJECTIVE
To evaluate the dose-response effects of metformin on QT and QTd of diabetic rats.


METHODS
Male Wistar rats were distributed in five groups: non-treated control (C), non-treated diabetics (D), diabetics treated with metmorfin at the doses of 3.5, 30 and 74 microg/kg/bw (DM 3.5, DM 30 and DM 74). Diabetes was induced by an alloxan injection (40 mg/kg, IV). EKG was recorded (days 1, 15 and 30) using four electrodes inserted into the subcutaneous layer of the paws. Both RR and QT intervals were measured, and then corrected QT and QT dispersion values were calculated.


RESULTS
The DM 3.5 and DM 30 groups showed a significant reduction of glycemia (p< 0.05) when compared with the high dose (DM 74). Rats of the DM 74 group presented prolonged QTc, QTd and QTcd intervals, whereas rats of the DM 3.5 and DM 30 groups presented less prolonged intervals.


CONCLUSIONS
Metformin at high doses provided greater dispersion of the QT interval probably because of the increased ventricular repolarization inhomogeneity, whereas at low doses decreased QT intervals were observed in diabetic rats.
Costa
Eunice Cristina da Silva
EC
Universidade Estadual de Campinas, Campinas, SP - Brasil. nicrisilva@uol.com.br
Gonçalves
Antonio Ari
AA
Areas
Miguel Arcanjo
MA
Morgabel
Rafael Gustavo Birochi
RG
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008133:Long QT Syndrome / Q000000981:diagnostic imaging*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D023421:Models, Animal; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar
D007004:Hypoglycemic Agents; D008687:Metformin