Glyburide enhancement of lactate production in ischemic heart is modified by preconditioning: an in vivo experimental study in pigs by microdialysis technique.
The concentrations of lactate, pyruvate, and adenosine, together with some of their derivatives, were determined in microdialysates from 12 pig hearts, 6 of which were subjected to preconditioning and 40 min of ischemia (index ischemia) and 6 of which were subjected to only 40 min of index ischemia. Two microdialysis probes were inserted in ischemic myocardium. Glyburide (10 mu M) in a modified isotonic Krebs-Ringer phosphate buffer was administered through one of the probes and plain isotonic phosphate buffer was administered through the other. Accordingly, the experimental setup permitted us to study the metabolic effects of glyburide on ischemic myocardium constituting two groups that were either preconditioned or unpreconditioned. The preconditioning effect was validated with area at risk and infarction area measurements in 12 other pigs. We noted no functional differences between the groups. In the unpreconditioned group glyburide infusion resulted in enhanced 60% lactate production during index ischemia. However, preconditioning attenuated the enhancing effect of glyburide on lactate production. The interplay between the effects of glyburide and preconditioning on ischemic myocardium is suggested to be dependent on the different modes of action on the K(+)(ATP) channel.
Wikström
B G
BG
Department of Cardiology, University Hospital, Uppsala, Sweden.
Ronquist
G
G
Waldenström
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D017202:Myocardial Ischemia / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology; D013552:Swine
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005905:Glyburide