Helium-induced preconditioning in young and old rat heart: impact of mitochondrial Ca(2+) -sensitive potassium channel activation.

摘要

BACKGROUND: The noble gas helium induces cardiac preconditioning. Whether activation of mitochondrial K(+) channels is involved in helium preconditioning (He-PC) is unknown. The authors investigated whether He-PC (1) is mediated by activation of Ca(2+) -sensitive potassium channels, (2) results in mitochondrial uncoupling, and (3) is age dependent. METHODS: Anesthetized Wistar rats were randomly assigned to six groups (n = 10 each). Young (2-3 months) control (Con) and aged (22-24 months) control animals (Age Con) were not treated further. Preconditioning groups (He-PC and Age He-PC) inhaled 70% helium for 3 x 5 min. The Ca(2+) -sensitive potassium channel blocker iberiotoxin was administered in young animals, with and without helium (He-PC+Ibtx and Ibtx). Animals underwent 25 min of regional myocardial ischemia and 120 min of reperfusion. In additional experiments, cardiac mitochondria were isolated, and the respiratory control index was calculated (state 3/state 4). RESULTS: Helium reduced infarct size in young rats from 61 +/- 7% to 36 +/- 14% (P < 0.05 vs. Con). Infarct size reduction was abolished by iberiotoxin (60 +/- 11%; P < 0.05 vs. He-PC), whereas iberiotoxin alone had no effect (59 +/- 8%; not significant vs. Con). In aged animals, helium had no effect on infarct size (Age Con: 59 +/- 7% vs. Age He-PC: 58 +/- 8%; not significant). Helium reduced respiratory control index in young animals (2.76 +/- 0.05 to 2.43 +/- 0.15; P < 0.05) but not in aged animals (Age Con: 2.87 +/- 0.17 vs. Age He-PC: 2.87 +/- 0.07; not significant). Iberiotoxin abrogated the helium effect on respiratory control index (2.73 +/- 0.15; P < 0.05 vs. He-PC) but had no effect itself on mitochondrial respiration (2.75 +/- 0.05; not significant vs. Con). CONCLUSION: Helium causes mitochondrial uncoupling and induces preconditioning in young rats via Ca(2+) -sensitive potassium channel activation. However, these effects are lost in aged rats.