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乳酸酸中毒:治疗对活体大鼠心脏细胞内pH值和能量代谢的影响。

Lactic acidosis: effect of treatment on intracellular pH and energetics in living rat heart.

作者信息

Zahler R, Barrett E, Majumdar S, Greene R, Gore J C

机构信息

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.

出版信息

Am J Physiol. 1992 May;262(5 Pt 2):H1572-8. doi: 10.1152/ajpheart.1992.262.5.H1572.

Abstract

Systemic acidemia may impair cardiac contractility and predispose to arrhythmias. Moreover, bicarbonate treatment may further depress cardiac performance and increase mortality. Whether changes in myocardial intracellular pH or energy metabolism underlie this diminished performance has not been clarified in the in vivo setting. Thus we investigated the effect of lactic acidosis and two proposed treatments on myocardial energetics and intracellular pH in anesthetized living rats. A previously validated 31P-labeled nuclear magnetic resonance (31P-NMR) spectroscopic technique using saturating pulses was used to follow myocardial intracellular pH, phosphocreatine (PCr), ATP, and inorganic phosphate (Pi). After obtaining baseline values, we infused lactic acid to achieve a level greater than 5 mM. We then added an infusion of either bicarbonate (n = 7) or saline (n = 5). During lactic acid infusion, arterial pH declined (from 7.27 to 7.07, P less than 0.0001), but myocardial intracellular pH did not change (7.13 vs. 7.07, P not significant). The ratio of PCr to Pi, however, decreased with acidemia (from 3.13 to 2.24, P = 0.004), suggesting impaired energy metabolism. Compared with saline, bicarbonate infusion restored systemic pH (from 7.08 to 7.29), but myocardial pH was unaltered. In addition, PCr/Pi declined further following bicarbonate treatment (1.41 vs. 2.42, P = 0.08) but not following saline. Thus, despite reversal of systemic acidemia, bicarbonate treatment was associated with more severe impairment of energy metabolism than saline. This suggests a mechanism for previously reported adverse cardiac effects of bicarbonate treatment.

摘要

全身性酸血症可能会损害心脏收缩力并易引发心律失常。此外,碳酸氢盐治疗可能会进一步抑制心脏功能并增加死亡率。在体内环境中,心肌细胞内pH值或能量代谢的变化是否是导致这种功能下降的原因尚未明确。因此,我们研究了乳酸酸中毒及两种建议的治疗方法对麻醉的活体大鼠心肌能量学和细胞内pH值的影响。我们使用一种先前经过验证的、采用饱和脉冲的31P标记核磁共振(31P-NMR)光谱技术来跟踪心肌细胞内pH值、磷酸肌酸(PCr)、三磷酸腺苷(ATP)和无机磷酸盐(Pi)。在获得基线值后,我们输注乳酸以使乳酸水平高于5 mM。然后,我们添加了碳酸氢盐输注(n = 7)或生理盐水输注(n = 5)。在乳酸输注期间,动脉pH值下降(从7.27降至7.07,P < 0.0001),但心肌细胞内pH值未发生变化(7.13对7.07,P无统计学意义)。然而,酸血症时PCr与Pi的比值下降(从3.13降至2.24,P = 0.004),提示能量代谢受损。与生理盐水相比,碳酸氢盐输注恢复了全身pH值(从7.08升至7.29),但心肌pH值未改变。此外,碳酸氢盐治疗后PCr/Pi进一步下降(1.41对2.42,P = 0.08),而生理盐水治疗后未出现这种情况。因此,尽管全身性酸血症得到了纠正,但与生理盐水相比,碳酸氢盐治疗与更严重的能量代谢损害相关。这提示了先前报道的碳酸氢盐治疗对心脏产生不良影响的一种机制。

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