Askenasy N, Navon G
School of Chemistry, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.
J Mol Cell Cardiol. 1998 Jul;30(7):1329-39. doi: 10.1006/jmcc.1998.0695.
The study aims to determine a possible relationship between intracellular water, energy metabolism, functional recovery and membrane permeability, during and after hypothermic cardiac preservation. Isolated rat hearts were stored for 12 h at 4 degrees C with University of Wisconsin (UW), St Thomas Hospital (ST) and Krebs-Henseleit (KH) solutions, and were reperfused for 1 h. Cellular volumes were measured by 1H NMR of water and 59Co NMR of the extracellular marker cobalticyanide, and energetic profiles by 31P NMR spectroscopy. Storage in ST solution reduced ischemic swelling from 2.50 +/- 0.06 to 2.73 +/- 0.09 (P < 0.001 v 3.56 +/- 0.10 ml/g dry weight in KH), while UW solution caused cellular shrinkage to 2.12 +/- 0.08 ml/g dry weight. Intracellular ATP concentrations and pH values were higher in UW as compared to ST solution. At reperfusion, hearts stored in ST shrank while those stored in UW expanded, resulting in similar intracellular volumes. Storage with UW was superior to ST in post-ischemic function 65 +/- 5% (P < 0.01 v 49 +/- 4% with ST) and in recovery of ATP 46 +/- 3% (P < 0.001 v 25 +/- 4% with ST). Storage with both ST and UW solutions did not prevent interstitial edema. Sarcolemmal membrane integrity, as assessed by cellular swelling in response to a hypo-osmotic shock (210 mmol/l), was significantly improved by ST and UW solutions as compared to KH (P < 0.05). Creatine kinase efflux was reduced by ST and UW as compared to KH (P < 0.05), and by UW as compared to ST (P < 0.05). Coronary flow was higher following storage with UW than ST solutions. 66 +/- 6 and 45 +/- 4%, respectively (P < 0.01). According to these data, the beneficial effects of UW and ST solutions on hypothermic ischemic storage of rat hearts included prevention of cellular edema and preservation of sarcolemmal membrane integrity. It is concluded: (a) UW and ST solutions reduce ischemic and reperfusion cellular volumes: (b) both solutions, and UW in particular were efficient in preservation of membrane integrity: (c) prevention of cellular edema is not the single or main mechanism responsible for the improved preservation with UW and ST solutions.
本研究旨在确定低温心脏保存期间及之后细胞内水、能量代谢、功能恢复与膜通透性之间可能存在的关系。将离体大鼠心脏分别用威斯康星大学(UW)溶液、圣托马斯医院(ST)溶液和克雷布斯 - 亨泽莱特(KH)溶液在4℃下保存12小时,然后再灌注1小时。通过水的1H NMR和细胞外标志物钴氰化物的59Co NMR测量细胞体积,并用31P NMR光谱测定能量谱。用ST溶液保存可使缺血肿胀从2.50±0.06降至2.73±0.09(与KH中3.56±0.10 ml/g干重相比,P<0.001),而UW溶液使细胞收缩至2.12±0.08 ml/g干重。与ST溶液相比,UW溶液中的细胞内ATP浓度和pH值更高。再灌注时,用ST溶液保存的心脏收缩,而用UW溶液保存的心脏扩张,导致细胞内体积相似。用UW溶液保存后心脏在缺血后功能方面优于ST溶液(65±5%,与ST溶液的49±4%相比,P<0.01),在ATP恢复方面也更优(46±3%,与ST溶液的25±4%相比,P<0.001)。用ST溶液和UW溶液保存均不能预防间质水肿。通过低渗休克(210 mmol/l)引起的细胞肿胀评估肌膜完整性,与KH溶液相比,ST溶液和UW溶液均能显著改善肌膜完整性(P<0.05)。与KH溶液相比,ST溶液和UW溶液均能减少肌酸激酶外流(P<0.05),且UW溶液比ST溶液更有效(P<0.05)。用UW溶液保存后冠状动脉血流量高于ST溶液,分别为66±6%和45±4%(P<0.01)。根据这些数据,UW溶液和ST溶液对大鼠心脏低温缺血保存的有益作用包括预防细胞水肿和保持肌膜完整性。得出以下结论:(a)UW溶液和ST溶液可减少缺血和再灌注时的细胞体积;(b)两种溶液,尤其是UW溶液在保持膜完整性方面有效;(c)预防细胞水肿不是UW溶液和ST溶液改善保存效果的唯一或主要机制。