<Original Articles>The Significance of Glutathione Peroxidase on Myocardial Protection in the rat Hearts : The Key of Clarify the Cause of Vulnerability to Reperfusion Injury in Infantile Cardiac Operations

Abstract

Selenium (Se) is an integral component of glutathione poeroxidase (GSHPx), and the serum selenium concentration is age-depend. We speculated that myocardial GSHPx had relation to reperfusion injury in open heart operations, especially in infants in whom GSHPx activity is low. This study correlated GSHPx activity with the serum and myocardial selenium concentrations in Wistar rats, which were divided into three groups, infants, Se-deficient rats, and control rats. Serum GSHPx activity in infant and Se-deficient rats (22. 7± 3. 5 U/g protein, 24. 6 ± 22. 2 U/g protein) was lower than that in controls (179 ± 12. 0 U/g protein). The serum selenium concentration in infant and Se-deficient rats (3. 81 ± 0. 81 μg/g protein, 2. 06 ± 1. 69 μg/g protein) was also lower than that in controls (7. 32 ± 2. 96 μg/g protein). The myocardial GSHPx activity was significantly lower in infants and Se-deficient rats (4. 76 ± 1. 05 × 10_-1 U/mg protein, 3. 38 ± 0. 32 × 10_-1 U/mg protein) than that in controls (8. 03 ± 0. 57 × 10_-1 U/mg protein). However, the myocardial selenium concentra tion in infants (1. 42 ± 0. 24 × 10_-1μg/mg protein) was significantly higher than that in the other groups (0. 31 ± 0. 06 × 10_-1 μg/mg protein, 0. 28 ± 0. 04 × 10_-1 μg/mg protein). Next, in Se-deficient and control rats, isolated hearts were perfused for aerobically with Krebs-Henseleit solution in the Langendorff mode for 15 minutes, followed by 60 minutes of global ischemia at 4°C and then reperfused for 30 minutes in a working mode. The hemodynamic parameters were measured. The aortic pressure, LV max dp/dt, aortic flow, cardiac output and stroke volume were significantly lower in the Se-deficient rats than those of the control rats. Immediately following these measurements, the hearts were frozend in liquid nitrogen, and the myocardial lipid peroxide (TBARS) concentration was assayed and found to be significantly higher in the Se-deficient rats. The lower myocardial GSHPx activity may play a important role in vulnerability to reperfusion injury in infants as in Se-deficient rats.

必須微量元素セレン(Se)は, フリーラジカルスカベンシャーの一つであるグルタチオンベルオキシダーゼ(GSHPx)の主要な構成成分である. 血清 Se 濃度は年齢により変化し新生児期, 乳児期は低い. このことが乳児期の関心術における再灌流障害に関与しているのではないかと推論した. ウィスター系ラットを乳児期ラット(乳児群), Se 欠乏食ラット(Se群), 対照成熟ラット(対照群)の3群に分けた乳児群, Se 群の血清 GSHPx 活性は, 対照群と比べ有意に低値を示した(順番に22. 7 ± 3. 5, 24. 6 ± 22. 2, 179. 0 ± 12. 0 U/g protein). 乳児群, Se 群の血清 S e濃度も同様に対照群と比べ有意に低値を示した(3. 81±0. 81, 2. 06 ± 1. 69, 7. 32 ± 2. 96 μg/g protein)・乳児群, Se 群の心筋 GSHPx 活性は対照群と比べ有意に低値を示した(4. 76 ± 1. 05 × 10_-1, 3. 38 ± 0. 32 × 10_-1, 8. 03 ± 0. 57× 10_-1 U/mg protein). しかし乳児群の心筋 Se 濃度は Se 群, 対照群と比べ有意に高値を示した(1. 42 ± 0. 24 × 10_-1, 0. 31 ± 0. 06 × 10_-1, 0. 28 ± 0. 04 × 10_-1 μg/mg protein). これとは別に Se 欠乏食ラットと対照成熟ラットの摘出心を用いて Neely JR らの working heart model により, 4°C 60分間の心停止後の心機能パラメーターを測定した. 大動脈圧, 左室 max dp/dt, 大動脈流量, 心拍出量, 一回拍出量は S e群で有意に低値を示した. また心筋内過酸化脂質(TBARS)濃度は, Se 群で有意に高値を示した. このことから, 心筋内 GSHPx 活性の低下は心筋の再灌流障害と非常に関連が深いことが示唆された.