Mitochondrial ATP dependent potassium channels mediate non-ischemic preconditioning by tachycardia in dogs.
Brief episodes of tachycardia without myocardial ischemia prior to a coronary occlusion decrease myocardial infarct size in dogs. This non-ischemic preconditioning is mediated by adenosine. Because ischemic preconditioning is mediated through ATP dependent potassium channels, particularly the mitochondrial ones, we studied whether non-ischemic preconditioning is also mediated through these channels. In anesthetized dogs heart rate was kept constant at 120 cycles/min and aortic pressure changes were damped. Myocardial infarction was induced by occlusion of the anterior descending coronary artery for 60 min and reperfusion for 270 min. In a control group the infarct size (necrotic volume/risk region volume x 100) was 15.8+/-1.5%. Preconditioning with five periods of tachycardia, 5 min in duration each at 213 cycles/min with intervening periods of 5 min of basal heart rate at 120 cycles/min, reduced the infarct size by 45.6% (p < 0.05) with respect to the control group. This effect was completely reverted by the blockade of ATP dependent potassium channels with glibenclamide or 5 hydroxydecanoate (a specific blocker of mitochondrial ATP dependent potassium channels) prior to preconditioning. These effects were not due to differences in collateral flow, risk region size or hemodynamic variables between the groups. These results show that mitochondrial ATP dependent potassium channels mediate non-ischemic preconditioning by tachycardia in dogs.
Macho
P
P
Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago.
Solis
E
E
Sánchez
G
G
Schwarze
H
H
Domenech
R
R
D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001783:Blood Flow Velocity; D003652:Decanoic Acids / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006339:Heart Rate; D006439:Hemodynamics; D006880:Hydroxy Acids / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009203:Myocardial Infarction; D009206:Myocardium / Q000378:metabolism*; D009336:Necrosis; D015221:Potassium Channels / Q000378:metabolism*; D013610:Tachycardia; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D007004:Hypoglycemic Agents; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D000241:Adenosine; D005905:Glyburide