Kusuoka H, Camilion de Hurtado M C, Marban E
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Am Coll Cardiol. 1993 Jan;21(1):240-8. doi: 10.1016/0735-1097(93)90743-k.
This study was conducted to elucidate the role of sodium/calcium (Na+/Ca2+) exchange in the mechanism of myocardial stunning.
Cellular Ca2+ overload mediated by Na+/Ca2+ exchange during reperfusion has been proposed as a mechanism for myocardial stunning. Because no specific pharmacologic inhibitors of the exchanger are available, we increased extracellular sodium concentration ([Na]o) during the early phase of reperfusion to decrease the driving force for Ca2+ influx through the pathway.
Isovolumetric left ventricular pressure and phosphorus-31 nuclear magnetic resonance spectra were measured in isolated perfused ferret hearts. Hearts were reperfused with different solutions after 15 min of total global ischemia at 37 degrees C.
Hearts reperfused with standard solution ([Na]o = 140 mmol/liter; the stunned hearts, n = 8) showed only 69 +/- 3% (mean +/- SEM) recovery of developed pressure relative to preischemic control developed pressure. In contrast, hearts reperfused with a high [Na]o solution ([Na]o = 268 mmol/liter) during the initial 5 min, followed by a gradual decrease of [Na]o to the standard level over 25 min (the high [Na]o group, n = 8) showed significantly better recovery of developed pressure (85 +/- 2%, p < 0.05 vs. the stunned hearts). In contrast, reperfusion with solutions in which the additional Na was substituted either by 256 mmol/liter sucrose or 128 mmol/liter choline chloride did not improve functional recovery, indicating that the beneficial effects of high [Na]o reperfusion are not due to either high ionic strength or high osmolarity. Phosphorus-31 nuclear magnetic resonance spectra showed no correlation between functional recovery and intramyocardial contents of phosphorus compounds or pH.
High [Na]o reperfusion protects against stunning, supporting the concept that Na+/Ca2+ exchange plays an important role in the mechanism of stunned myocardium.
本研究旨在阐明钠/钙（Na+/Ca2+）交换在心肌顿抑机制中的作用。
再灌注期间由Na+/Ca2+交换介导的细胞内钙超载已被提出作为心肌顿抑的一种机制。由于没有该交换体的特异性药理抑制剂，我们在再灌注早期增加细胞外钠浓度（[Na]o）以降低通过该途径的钙内流驱动力。
在离体灌注的雪貂心脏中测量等容左心室压力和磷-31核磁共振波谱。心脏在37℃完全性全心缺血15分钟后用不同溶液进行再灌注。
用标准溶液（[Na]o = 140 mmol/升；顿抑心脏，n = 8）再灌注的心脏相对于缺血前对照舒张期压力仅显示69±3%（平均值±标准误）的舒张期压力恢复。相比之下，在最初5分钟用高[Na]o溶液（[Na]o = 268 mmol/升）再灌注，随后在25分钟内将[Na]o逐渐降至标准水平（高[Na]o组，n = 8）的心脏显示出明显更好的舒张期压力恢复（85±2%，与顿抑心脏相比p < 0.05）。相反，用额外的钠被256 mmol/升蔗糖或128 mmol/升氯化胆碱替代的溶液进行再灌注并未改善功能恢复，表明高[Na]o再灌注的有益作用不是由于高离子强度或高渗透压。磷-31核磁共振波谱显示功能恢复与心肌内磷化合物含量或pH之间无相关性。
高[Na]o再灌注可预防顿抑，支持Na+/Ca2+交换在心肌顿抑机制中起重要作用的观点。
