Belló-Klein A, Oliveira A R, Miranda M F, Irigoyen M C, Homem-de-Bittencourt P I, Llesuy S, Belló A A
Departamento de Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
Braz J Med Biol Res. 1997 Nov;30(11):1337-42. doi: 10.1590/s0100-879x1997001100013.
Hydrogen peroxide (H2O2) perfused into the aorta of the isolated rat heart induces a positive inotropic effect, with cardiac arrhythmia such as extrasystolic potentiation or cardiac contractures, depending on the dose. The last effect is similar to the "stone heart" observed in reperfusion injury and may be ascribed to lipoperoxidation (LPO) of the membrane lipids, to protein damage, to reduction of the ATP level, to enzymatic alterations and to cardioactive compounds liberated by LPO. These effects may result in calcium overload of the cardiac fibers and contracture ("stone heart"). Hearts from male Wistar rats (300-350 g) were perfused at 31 degrees C with Tyrode, 0.2 mM trolox C, 256 mM H2O2 or trolox C + H2O2. Cardiac contractures (baseline elevation of the myograms obtained) were observed when hearts were perfused with H2O2 (Tyrode: 5.9 +/- 3.2; H2O2: 60.5 +/- 13.9% of the initial value); perfusion with H2O2 increased the LPO of rat heart homogenates measured by chemiluminescence (Tyrode: 3,199 +/- 259; H2O2: 5,304 +/- 133 cps mg protein-1 60 min-1), oxygen uptake (Tyrode: 0.44 +/- 0.1; H2O2: 3.2 +/- 0.8 nmol min-1 mg protein-1) and malonaldehyde (TBARS) formation (Tyrode: 0.12 +/- 0; H2O2: 0.37 +/- 0.1 nmol/ml). Previous perfusion with 0.2 mM trolox C reduced the LPO (chemiluminescence: 4,098 +/- 531), oxygen uptake (0.51 +/- 0) and TBARS (0.13 +/- 0) but did not prevent the H2O2-induced contractures (33.3 +/- 16%). ATP (Tyrode: 2.84 +/- 0; H2O2: 0.57 +/- 0) and glycogen levels (Tyrode: 0.46 +/- 0; H2O2: 0.26 +/- 0) were reduced by H2O2. Trolox did not prevent these effects (ATP: 0.84 +/- 0 and glycogen: 0.27 +/- 0). Trolox C is known to be more effective than alpha-tocopherol or gamma-tocopherol in reducing LPO though it lacks the phytol portion of vitamin E to be fixed to the cell membranes. Trolox C, unlike vitamin A, did not prevent the glycogen reduction induced by H2O2. Trolox C induced a positive chronotropic effect that resulted in higher energy consumption. The reduction of energy level seemed to be more important than LPO in the mechanism of H2O2-induced contracture.
将过氧化氢（H₂O₂）灌注到离体大鼠心脏的主动脉中会产生正性肌力作用，并伴有心律失常，如早搏增强或心脏挛缩，具体取决于剂量。最后一种效应类似于在再灌注损伤中观察到的“石心”，可能归因于膜脂的脂质过氧化（LPO）、蛋白质损伤、ATP水平降低、酶改变以及LPO释放的心脏活性化合物。这些效应可能导致心肌纤维钙超载和挛缩（“石心”）。用含有0.2 mM生育三烯酚C、256 mM H₂O₂或生育三烯酚C + H₂O₂的台氏液在31℃下灌注雄性Wistar大鼠（300 - 350 g）的心脏。当用H₂O₂灌注心脏时观察到心脏挛缩（获得的肌动图基线升高）（台氏液：5.9±3.2；H₂O₂：初始值的60.5±13.9%）；用H₂O₂灌注增加了通过化学发光测量的大鼠心脏匀浆的LPO（台氏液：3,199±259；H₂O₂：5,304±133 cps mg蛋白⁻¹ 60分钟⁻¹）、氧摄取（台氏液：0.44±0.1；H₂O₂：3.2±0.8 nmol分钟⁻¹ mg蛋白⁻¹）和丙二醛（TBARS）形成（台氏液：0.12±0；H₂O₂：0.37±0.1 nmol/ml）。先前用0.2 mM生育三烯酚C灌注可降低LPO（化学发光：4,098±531）、氧摄取（0.51±0）和TBARS（0.13±0），但不能防止H₂O₂诱导的挛缩（33.3±16%）。H₂O₂降低了ATP（台氏液：2.84±0；H₂O₂：0.57±0）和糖原水平（台氏液：0.46±0；H₂O₂：0.26±0）。生育三烯酚不能防止这些效应（ATP：0.84±0和糖原：0.27±0）。已知生育三烯酚C在降低LPO方面比α-生育酚或γ-生育酚更有效，尽管它缺乏维生素E固定到细胞膜上的叶绿醇部分。与维生素A不同，生育三烯酚C不能防止H₂O₂诱导的糖原减少。生育三烯酚C诱导正性变时作用，导致更高的能量消耗。在H₂O₂诱导挛缩的机制中，能量水平的降低似乎比LPO更重要。
