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Concerning the effect of the K+ channel blocking agent glibenclamide on ischaemic and reperfusion arrhythmias
1Department of Pharmacology, University of Freiburg, Germany.
Insights
Glibenclamide (glyburide), a drug modulating ATP-dependent K+ channels, did not prevent cardiac arrhythmias in rat hearts during ischemia and reperfusion. Instead, it intensified arrhythmias and decreased coronary flow, suggesting pro-arrhythmic effects.
Area of Science:
- Cardiovascular Pharmacology
- Cardiac Electrophysiology
Background:
- ATP-dependent K+ channel modulators' effects on ischemia-induced cardiac arrhythmias are poorly understood.
- Glibenclamide (glyburide) was investigated as a potential antiarrhythmic due to its antagonism of ischemic K+ efflux.
Purpose of the Study:
- To evaluate the effects of glibenclamide on cardiac arrhythmias induced by coronary occlusion and reperfusion in rat hearts.
- To investigate the impact of glibenclamide on coronary flow and adenosine release during ischemia and reperfusion.
Main Methods:
- Rat hearts subjected to coronary occlusion and reperfusion.
- Perfusion with glibenclamide (0.1 and 1.0 µmol/l).
- Measurement of arrhythmias, coronary flow, and adenosine release. Sodium nitroprusside and gallopamil used for comparison.
Main Results:
- Glibenclamide did not antagonize ischemia or reperfusion arrhythmias; it intensified them.
- Glibenclamide significantly decreased coronary flow and increased adenosine release.
- Sodium nitroprusside partially reversed the coronary flow reduction but not arrhythmias.
- Gallopamil (a Ca2+ channel blocker) increased coronary flow, reduced adenosine release, and antagonized arrhythmias.
Conclusions:
- Glibenclamide does not exhibit antiarrhythmic effects against ischemia-induced cardiac arrhythmias.
- Glibenclamide demonstrates pro-arrhythmic properties and negatively impacts coronary hemodynamics.
- The findings do not support the use of glibenclamide as an antiarrhythmic agent in this context.
Abstract:
Reports on effects of ATP-dependent K+ channel modulating drugs on ischaemia-induced cardiac arrhythmias have been scarce and contradictory. The channel blocking agent glibenclamide (glyburide) has been considered as an antiarrhythmic candidate, because it antagonizes the ischaemic K+ efflux and the shortening of the refractory period. In the present investigation its effects were tested, therefore, in rat hearts with coronary occlusion and reperfusion. In untreated hearts, tachyarrhythmias occurred during the reperfusion, and less pronounced during the coronary occlusion itself. Large amounts of adenosine and its degradation products were released during the coronary reperfusion, particularly from hearts which developed ventricular fibrillation. Glibenclamide (0.1 and 1.0 micromol/l perfusion fluid) neither antagonized the ischaemic nor the reperfusion arrhythmias. Ischaemic arrhythmias were even intensified. Also in control hearts without coronary occlusion, pro-arrhythmic effects of glibenclamide were observed. Furthermore, the coronary flow was considerably decreased by the drug, and the release of adenosine and its metabolites was significantly increased. Sodium nitroprusside antagonized the glibenclamide-induced decrease in the coronary flow, but did not prevent the arrhythmias. The Ca2+ channel blocking agent gallopamil increased the coronary flow, decreased the adenosine release, and antagonized the arrhythmias in hearts with and without glibenclamide. In conclusion, the present findings do not favour the idea of an antiarrhythmic effect of glibenclamide. Rather, some propensity to the occurrence of arrhythmias can be produced by the drug.