离体心脏严重低钾时的磁共振电子分光镜研究

NMR spectroscopy studies of severe hypokalemia in the isolated rat heart

目的 研究低血钾是如何损害心肌细胞。方法 将 2 4只大白鼠离体心脏随机分成四组 ,即无钾正常钙灌注组 ,无钾低钙灌注组 ,低钾正常钙灌注组和低钾高钙灌注组 ,另 6例作为对照组。先正常灌注液灌注 30分钟 ,使心脏功能维持正常 ;以后实验灌注 30分钟 ,最后恢复正常灌注 30分钟。整个过程用磁共振电子分光镜技术连续监测心肌细胞的三磷酸腺苷 (ATP)、磷酸肌酸 (PCr)、无机磷酸 (Pi)及心肌细胞内Ph (Phi)的浓度变化 ;同时用心电图和多道心脏电生理仪监测心电图、心律及其血液动力学变化。实验完成后立即将离体心脏液氮冷冻 ,用化学方法提取线粒体 ,最后用原子吸收分光镜检查心肌细胞内的线粒体及其钙含量。结果 低钾导致心肌细胞内ATP ,PCr合成明显减少 ,同时伴有心肌细胞内酸中毒 ,而Pi明显增加 ,其程度与低钾程度呈正比。当恢复正常灌注之后 ,其能量代谢紊乱。心律失常及心功能不能恢复 ,当用低钾高钙灌注液灌注时 ,此种变化更为明显。结论 低钾导致心肌细胞线粒体呼吸功能不全 ,引起心肌细胞线粒体能量产生障碍 ,出现ATP ,PCr下降 ,Pi升高和细胞内酸中毒 ,从而导致心律紊乱 ,心功能下降 ,心室纤颤和心脏停搏。这似可说明洋地黄过量伴潜在低钾及低钙时 ,如不补足钾就补钙所造成的危害及其机理 ,为临?

Objective We performed the following studies to examine the effects and mechanisms of hypokalemia on cardiac energy metabolism using NMR spectroscopy technique at the cell-molecule level.Methods 30 isolated rat hearts were studied.A Langendorff heart preparation modified for serial nuclear magnetic resonance spectroscopy(NMRS)studies was employed.The isolated rat hearts were perfused with different potassium and calcium concentration perfusion under out-body circuit system.At the same time,the energy metabolism of myocardial cell and the function of isolated heart were monitored continuously using NMRS and a latex balloon filled in left heart ventricle.Mitochondrial calcium content was subsequently measured with atomic absorption spetroscopy(AAS).Results Perfusion of isolated heart with media lacking or low potassiun for 30 minutes caused rapid decrease in creatine phosphate (Pcr)and adenosine triphosphate(ATP)as well as reciprocal increase in inorganic phosphate(Pi)concentration.Cardiac mitochondria got from isolated rat heart cell demonstrated calcium loading and respiratory dysfunction of heart cell.Conclusion Reduction or increase in perfusate potassiun or/and calcium interrupte seriously the energy metabolism and acid-base equilibrium of myocardial cells.This is very important in treatment of patients with heart failure using digitoxin medicine.