维拉帕米对离体大鼠心脏缺血-再灌注损伤保护作用的31P核磁共振研究

为评价维拉帕米(Ver)防治心脏缺血-再灌注损伤的作用,采用³¹P核磁共振(^3lP NMR)技术对大鼠心肌缺血前,缺血过程中及缺血后高能磷化物的含量及细胞内pH (pH_i)的变化过程进行了动态跟踪测定,离体心脏于37℃下平衡灌流30min,停止灌流30min,再灌注30min.灌流液中始终含有Ver (0.2μmol·L^-1).Ver可使再灌注后心脏的冠脉流量有较高程度的恢复,^3lP NMR测定显示Ver可使心脏产生代谢上的改善作用.缺血10min后对照组心脏即检测不到磷酸肌酸(PCr),而Ver组心脏PCr仍保持在缺血前的20%.缺血过程中治疗组比未治疗组心脏ATP下降减缓,至缺血结束时心肌ATP分别为缺血前的53%和34%.再灌注后两组心肌的ATP均未回升,但Ver使PCr的恢复显著提高(P<0.05),给药心脏PCr/P_i(无机磷酸盐)无论在缺血前或再灌注阶段,都非常显著(P<0.01)地高于对照组心脏.Ver还可显著减轻缺血过程中的酸中毒并防止再灌注后心肌出现严重酸化的区域.

~(31)P NMR STUDIES ON PROTECTIVE EFFECTS OF VERAPAMIL AGAINST THE ISCHEMIA-REPERFUSION INJURED ISOLATED RAT HEARTS

To assess the myocardial effects of verapamil (Ver) pre-treatment against is-chemia-reperfusion injury, ³¹P NMR was used to sequentially follow the time courses of high energy phosphates (HEP) contents and intracellular pH(pH_i) of the rat myocardium before, during and after total ischemia. After 30min of equilibration, the perfustion of isolated hearts was stopped for 30min and subsequent reperfusion lasted for 30min at 37℃.Ver (0.2μmol·L^-1) was added to the perfusate throughout the experiment. Ver induced a more complete restoration of coronary flow following reperfusion. ³¹P NMR determination suggested metabolically beneficial effects induced by Ver administration. Phosphocreatine (PCr) became undetectable after 10min of ischemia in control hearts, but remained at 20%of its preischemic levels in Ver group. Adenosine triphosphate (ATP) decreased more slowly in treated than in untreated hearts during ischemia, with the end-ischemic levels of ATP were 53% and 34% respectively. Myocardial ATP was not replenished afer reperfusion in both groups, but Ver induced a significant (P < 0.05) higher recovery of PCr on reflow.PCr/P_i (inorganic phosphate) ratios were very significantly (P < 0.01) higher for treated hearts than for control hearts during both the first 10min of ischemia and the reperfusion stage. Ver was also found to significantly attenuate the acidosis during ischemia and prevent the appearance of very acidic areas of the myocardium after reperfusion.