Ca2＋sensitizer pimobendanによる低灌流虚血後の再灌流傷害の軽減ならびに心機能回復改善

Ca2+Sensitizer, Pimobendan, Attenuates Myocardial Injury in Low-flow Ischemic but not in Total Ischemic Hearts

　虚血・再灌流においてCa^2＋sensitizerが有害か有益かは議論のあるところである．ラット摘出心をLangendorff手技にて灌流した．10分の前灌流の後2ml／min 30分間の低流量虚血（LF）か25分間の完全虚血（TI）を行い，30分間の再灌流を行った．Ca^2＋sensitizerであるpimobelldan 50μMを低流量虚血時に用いた群をLFp，完全虚血前に10分間用いたものをTlpとした．LFとLFpではLFpが左室収縮期圧（62.4％vs 93.6％），発生圧（57.0％vs 95.3％），左室圧微分陽性値（53.2％vs 97.3％），CK流出量（458.7vs 122.1IU／g dwt）と改善がみられた．しかし，エネルギー代謝産物に関しては両群に有意差はなかった．TIとTIp間では，左室圧に関し有意差はなく，いずれも低値であった．これらの結果はpimobendanがstunningやhibernationに繋がるような軽い虚血に対しては有益に働き，不可逆性要素の強い虚血に対しては有害であることを示唆した．

Whether Ca²⁺ sensitizer is beneficial in cases of is-chemic myocardium is still controversial. We examinedthe effect of pimobendan on ischemic-reperfusion injury.Isolated SD rat hearts were subjected to 30 minutes oflow-flow ischemia (LF) or 25 minutes of total ischemia(TI) after 10 minutes of preperfusion, and were follo-wed by 30 minutes of reperfusion. In another twogroups we used 50,uM of pimobendan during LF (LFp)or 10 minutes preperfusion before TI (TIp). LV systolicpressure (62.4% vs 93.6% of each control value), devel-oped pressure (57.0% vs 95.3%), and peak positive dp/dt (53.2% vs 97.3%) recovered better with reducedrelease of CK (458.7 vs 122.1 IU/g dwt) in the LFp groupthan in the LF group. ATP, creatine phosphate (CP)and lactate after reperfusion were the same in both theLF and the LFp group. Although there was no differencein recovery of LV function between the TI and TIpgroups, recovery of CP decreased and ⁴⁵Ca²⁺uptake andrelease of CK were greater in the TI group. In heartswith low-flow ischemia and reperfusion, pimobendanenhanced recovery of LV function without deteriorationof energy metabolism or Ca²⁺ overload. These resultssuggest that pimobendan may be beneficial for lesssevere ischemia causing myocardial stunning or hiberna-tion but not for more severe ischemia resulting in ir-reversible injury.