Caspi J, Coles J G, Benson L N, Herman S L, Diaz R J, Augustine J, Brezina A, Kolin A, Wilson G J
Division of Cardiovascular Surgery, Hospital For Sick Children, Toronto, Ontario, Canada.
J Thorac Cardiovasc Surg. 1993 Mar;105(3):525-31.
Neonates undergoing heart surgery are exposed to high levels of circulating catecholamines. Our objective was to determine to what extent administration of magnesium counters epinephrine-induced cardiotoxicity. We assessed left ventricular function (pressure-volume data obtained by the conductance catheter/micromanometer technique) and ultrastructure in newborn pigs 3 to 5 days of age before and after administration of epinephrine alone (2 micrograms/kg/min, group A, n = 6) and simultaneously with magnesium sulfate (8 mmol/L, 5 ml/hr, group B, n = 6). Plasma levels of magnesium were maintained at 200% to 250% of control, and ionized calcium was maintained at normal levels. During administration of epinephrine, there was a significant increase in end-systolic elastance from 8.9 +/- 2 to 15 +/- 3 mm Hg/ml in group A and from 7.8 +/- 2 to 16 +/- 3 mm Hg/ml in group B (p < 0.05). This increase was accompanied by an increase in chamber stiffness index (p < 0.05) and shortening of the time constant of isovolumic relaxation (p < 0.05; group A, 19 +/- 3 to 13 +/- 3 msec; Group B, 20 +/- 2 to 15 +/- 2 msec). After epinephrine was discontinued, however, systolic and diastolic indexes returned to baseline levels in group B, whereas group A exhibited a significant reduction in end-systolic elastance (5 +/- 1 mm Hg/ml; p < 0.05) and an increase in chamber stiffness index (0.7 +/- 0.08 versus 0.4 +/- 0.1 ml-1; p < 0.05) and time constant (25 +/- 1 versus 19 +/- 3 msec). Left ventricular dysfunction in group A was associated with focal sarcolemmal rupture and mitochondrial swelling, whereas only minor reversible changes (microvesicular lipid accumulation) were seen in group B. We conclude that magnesium has a protective effect against epinephrine-induced cardiotoxicity because of its blocking action on calcium influx of ionized calcium and could be of therapeutic benefit in the perioperative period.
接受心脏手术的新生儿会暴露于高水平的循环儿茶酚胺中。我们的目的是确定镁的给药在多大程度上对抗肾上腺素诱导的心脏毒性。我们评估了3至5日龄新生猪在单独给予肾上腺素（2微克/千克/分钟，A组，n = 6）以及同时给予硫酸镁（8毫摩尔/升，5毫升/小时，B组，n = 6）前后的左心室功能（通过电导导管/微测压技术获得的压力-容积数据）和超微结构。血浆镁水平维持在对照值的200%至250%，离子钙维持在正常水平。在给予肾上腺素期间，A组的收缩末期弹性从8.9±2显著增加至15±3毫米汞柱/毫升，B组从7.8±2增加至16±3毫米汞柱/毫升（p<0.05）。这种增加伴随着心室僵硬度指数的增加（p<0.05）和等容舒张时间常数的缩短（p<0.05；A组，19±3至13±3毫秒；B组，20±2至15±2毫秒）。然而，在停用肾上腺素后，B组的收缩和舒张指数恢复到基线水平，而A组的收缩末期弹性显著降低（5±1毫米汞柱/毫升；p<0.05），心室僵硬度指数增加（0.7±0.08对0.4±0.1毫升-1；p<0.05）和时间常数增加（25±1对19±3毫秒）。A组的左心室功能障碍与局灶性肌膜破裂和线粒体肿胀有关，而B组仅观察到轻微的可逆性变化（微泡脂质积聚）。我们得出结论，镁因其对离子钙钙内流的阻断作用而对肾上腺素诱导的心脏毒性具有保护作用，并且在围手术期可能具有治疗益处。
