Glibenclamide effects on reperfusion-induced malignant arrhythmias and left ventricular mechanical recovery from stunning in conscious sheep

Abstract

Glibenclamide infusion resulted in adverse cardiovascular effects. The combined deleterious effects on reperfusion-induced arrhythmias and on myocardial recovery from stunning could be the cause of the unexplained high mortality in diabetic patients treated with sulfonylurea derivatives. The mechanism involved seems to be the blockade of the cardiac ATP sensitive potassium (K-ATP) channel.

Thrombin Receptor and Ventricular Arrhythmias after Acute Myocardial Infarction

“…On the other hand, there are disputes about the role of K ATP in cardiac arrhythmias during an acute ischemic insult. Most of the evidence supports a scenario whereby opening of myocardial K ATP channels by hypoxia and ischemia subsequently increases potassium efflux, which leads to a shortening of the action potential duration, a depolarization of the membrane by extracellular potassium accumulation, and inhomogeneities in repolarization; this scenario creates a substrate for reentry (28)(29)(30)(31). These potentially arrhythmogenic mechanisms are implicated in the genesis of ischemic arrhythmias.…”

Inhibition of Na+-K+ Pump and L-Type Ca2+ Channel by Glibenclamide in Guinea Pig Ventricular Myocytes

“…Similar inhibitory effect of 10 to 100 M glibenclamide on the I Ca,L was also observed in rat aortic smooth muscle (Yoshitake et al, 1991;Bian and Hermsmeyer, 1994). Some investigators did not observe a negative inotropic effect of glibenclamide in the heart (Sykes et al, 1977;Del Valle et al, 2001). They applied glibenclamide via oral administration or intravenous injection, and the concentration of glibenclamide in plasma might be around 0.5 to 2.5 M (Del Valle et al, 2001).…”

“…Some investigators did not observe a negative inotropic effect of glibenclamide in the heart (Sykes et al, 1977;Del Valle et al, 2001). They applied glibenclamide via oral administration or intravenous injection, and the concentration of glibenclamide in plasma might be around 0.5 to 2.5 M (Del Valle et al, 2001). Our results also revealed that glibenclamide had no significant effect on contraction at concentrations Ͻ 1 M, and the threshold concentration for the effect was between 1 and 10 M (Fig.…”

The Effect of Nicorandil on Small Intestinal Ischemia–Reperfusion Injury in a Canine Model

“…Regarding the role of glibenclamide on IR injury, del Valle et al reported that glibenclamide had combined proarrhythmic and cardiodepressant affects in cardiac IR injury models using sheep [32]. We could not find the reports of whether glibenclamide directly affects intestinal IR injury.…”