Ischemia-reperfusion injury and oxygen-derived free radicals in isolated perfused rat heart: sarcoplasmic reticulum Ca2+ handling dysfunction.:<I>sarcoplasmic reticulum Ca<SUP>2+</SUP> handling dysfunction</I>
スポンサーリンク
概要
- 論文の詳細を見る
It has been postulated that disturbances of ionic homeostasis may determine the vulnerability of the heart to reperfusion-induced injury, and that reactive oxygen species produced during reperfusion, cause oxidant stress to membrane protein or lipid that leads to disturbances of ionic homeostasis and arrhythmias. To test this hypothesis, we studied the efficacies of various reactive oxygen species scavengers in reducing ischemia-reperfusion (I/R) -induced myocardial injury in isolated perfused rat hearts. The effect of <I>in vitro</I> free radical generating system consisting of hypoxanthine (hyX) and xanthine oxidase (XO) on sarcoplasmic reticulum (SR) function was also investigated. In I/R hearts, the contractile function and coronary flow were reduced; reperfusion with histidine or a cocktail of superoxide dismutase (SOD) -catalase-mannitol resulted in significant protection against the effect of I/R. The incidence of arrhythmias during reperfusion was 100% in I/R hearts; the duration of arrhythmias was shortened with histidine or with SOD-catalase-mannitol. The decreased duration of normal sinus rhythm in I/R hearts was also protected with histidine or SOD-catalase-mannitol. The SR function assessed by oxalate-supported Ca<SUP>2+</SUP> uptake rate in cell free preparations in the presence or absence of ruthenium red, a selective SR Ca<SUP>2+</SUP>-release channel blocker, was depressed by exposure to hyX-XO reaction. The observed effect of hyX-XO was SOD-inhibitable and was protected by SOD-catalase-mannitol. In samples where the Ca<SUP>2+</SUP>-release channel was blocked with ruthenium red, no changes in Ca<SUP>2+</SUP> uptake rates were noted after ischemia only; the Ca<SUP>2+</SUP> uptake rates in the presence of ruthenium red decreased in samples from ischemia-reperfused hearts, suggesting Ca<SUP>2+</SUP>-release channel dysfunction caused by oxygen-derived free radicals generated during reperfusion. Exposure of isolated heavy SR to hyX-XO reaction produced potent increase in Ca<SUP>2+</SUP> efflux; the effect of hyX-XO reaction was protected by SOD or by established optimal conditions for specific closure of heavy SR Ca<SUP>2+</SUP>-release channel by ryanodine. Based on these lines of results, we conclude that the action of reactive oxygen species (possibly, superoxide radicals or singlet molecular oxygen) may be mediated in part through SR Ca<SUP>2+</SUP>-release channel, thereby causing Ca<SUP>2+</SUP> overload linked to arrhythmogenic electrophysiological changes.
- 日本炎症・再生医学会の論文
日本炎症・再生医学会 | 論文
- 新規キノリノン誘導体TA-270の炎症性気道疾患に対する効果
- Salazosulphapyridine, Predonizolone の好中球機能に及ぼす影響と Sodium ferrous citrate との併用効果についての検討
- Sodium ferrous citrate の好中球機能に及ぼす影響
- Mesalazine(Pentasa) の好中球機能に及ぼす影響と Sodium ferrous citrate(SFC) との併用効果についての検討
- 非ウイルスベクターによる細胞標的法の開発