Superoxide Dismutase（SOD）とCatalase（CAT）併用の再灌流心の心機能回復，Ca2＋過剰およびエネルギー代謝回復に及ぼす二相性効果

Biphasic effects of a combined administration of SOD and CAT on Ca overload and recovery of function and metabolites

　〔目的〕SODとCATの併用が虚血心再灌流時のCa^2＋過剰発生，心機能およびエネルギー代謝回復に与える影響を検討する。〔方法〕ラット摘出心の30分完全虚血と30分再灌流を作成，虚血前後にSOD（5×10⁴−40×1O⁴U／l）とCAT（7.5×10⁴−60×10⁴U／l）を併用し，対照群と比較した。〔結果〕対照群では再灌流による左室発生圧の回復は30％で左室拡張末期圧の著明な上昇，ATPとCPは各々非虚血時の40％，60％へ低下，Ca^2＋摂取量は13倍に増加した。低濃度SODとCAT投与（各々5×10⁴，7.5×10⁴U／l）はCa^2＋摂取量の増加を20％減少させ，左室発生圧は虚血前値の60％まで回復したが，エネルギー代謝は改善しなかった。これに対して高濃度SOD＋CAT（各々40×10⁴，60×10⁴U／l）併用では逆に心機能回復は低下しCa^2＋過剰は増強され（14倍），エネルギー代謝の回復も増悪した。〔結論〕SOD＋CAT併用効果は二相性であり，安易な高濃度での使用はかえって再灌流傷害の増悪を招く危険性がある。

The present study was performed to clarify whether the combination of superoxide dismutase (SOD) and catalase (CAT) can reduce Ca²⁺ over-load and improve recovery of function and meta-bolites during reperfusion in isolated globally ischemic rat hearts. In non-treated hearts, left ventricular developed pressure (LVDP) recovered to only 30% of the preischemic value with ele-vation of left ventricular end-diastolic pressure (LVEDP) after 30 min of reperfusion following 30 min of global zero-flow ischemia. ATP and CP fell by 40% and 60%, respectively with 13 fold increase in Ca²⁺ uptake. A combined administration of SOD and CAT at low concentrations improved recovery of function (LVDP to 60%), reduced Ca ²⁺ uptake (10 fold) without any improvement in high energy phosphates. However a combination of SOD and CAT at higher concentrations did not improve, or even deteriorate functional and metabolic re-covery with increased Ca overload (12 to 14 fold). These results indicated that the extracellular free radical scavengers, SOD and CAT, had a biphasic effect on reperfusion injury and could be partially beneficial at low concentrations.