Effects of barium and 5-hydroxydecanoate on the electrophysiologic response to acute regional ischemia and reperfusion in rat hearts.
The aim of this work was to investigate the role of the inward rectifying (K1) and the sarcolemmal ATP-sensitive K+ (K-ATP) channels in the electrical response to regional ischemia and the subsequent development of ventricular tachyarrhythmias on reflow (RA). Surface electrograms (ECG) and the transmembrane potential from subepicardial left ventricular cells were recorded in spontaneously beating rat hearts perfused with buffer alone (controls) or exposed to 100 microM BaCl2 or 100 microM 5-hydroxydecanoate (5-HD) to block either K1 or K-ATP channels respectively. After 20 min of equilibration and 10 min of control recordings, the left anterior descending coronary artery was occluded for 10 min. This was followed by reperfusion. The effects of regional ischemia as well as those of reperfusion (10 min) were recorded throughout. In the three groups, ischemia induced a modest decrease in heart rate and a sharp reduction in resting potential within 3 min. The latter as well as the accompanying depression of propagated electrical activity were enhanced by Ba2+. A partial recovery of the resting potential was observed in all groups during the last 2 min of coronary occlusion. Concomitantly, a slight reduction in the action potential duration was found in the control hearts. This effect was blocked by 5-HD. Under Barium the action potential duration increased by a factor of 3 and its ischemic variations were minimized. Severe sustained ventricular tachyarrhythmias developed on reflow in the controls and in the 5-HD exposed hearts. Barium limited the duration of arrhythmic episodes to a few seconds. Our data indicate that the initial electrical effects of ischemia are unrelated to activation of ATP sensitive K+ channels and that gK1 dominates the K+ membrane conductance at this stage. Furthermore, they show that action potential lengthening limits the duration of arrhythmic episodes triggered by reperfusion. This suggests that electrical heterogeneity plays an important role in the perpetuation of reperfusion arrhythmias.
Baiardi
Gustavo
G
Department of Morphophysiology, University of Cuyo, Mendoza, Argentina.
Zumino
Amira Ponce
AP
Petrich
Elena Ruiz
ER
D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology*; D003652:Decanoic Acids / Q000494:pharmacology*; D004569:Electroencephalography; D004594:Electrophysiology / Q000379:methods*; D006321:Heart / Q000502:physiology; D006880:Hydroxy Acids / Q000494:pharmacology*; D007511:Ischemia; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D015221:Potassium Channels / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015427:Reperfusion Injury; D017180:Tachycardia, Ventricular / Q000473:pathology; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; D001464:Barium; C052853:5-hydroxydecanoic acid