Jeffrey F M, Storey C J, Malloy C R
Mary Nell and Ralph B. Rogers NMR Center, University of Texas Southwestern Medical Center, Dallas.
Basic Res Cardiol. 1992 Nov-Dec;87(6):548-58. doi: 10.1007/BF00788665.
Depletion of high-energy phosphates, accumulation of inorganic phosphate and intracellular acidosis have each been proposed as important events in the transition from reversible to irreversible ischemic injury. To assess whether each variable is predictive of functional recovery on reperfusion, these were measured in the isolated isovolumic rat heart using 31P NMR. Perfused hearts were subjected to either 10, 12 or 40 min of normothermic ischemia followed by 40 min of reperfusion. Hearts were then freeze-clamped for further analysis of phosphate metabolites by NMR and ion chromatography. High-energy phosphates, Pi, phosphomonoesters and pH were measured by 31P NMR spectroscopy at 2 minute intervals. Heart rate and developed pressure were monitored simultaneously. All hearts undergoing 10 min of ischemia and 40% of hearts subjected to 12 min of ischemia demonstrated good functional recovery. The remainder of hearts ischemic for 12 min went into contracture on reperfusion with little return of function. Hearts subject to 40 min of ischemia went into ischemic contracture and showed no recovery on reperfusion. Intracellular pH, [ATP], and [Pi] measured prior to reperfusion did not predict the extent of recovery. However, phosphomonoesters were detected prior to reperfusion in all hearts that did not recover well, but were not observed in hearts that showed good mechanical recovery. Analysis of tissue extracts by 31P NMR and ion chromatography indicated that the most prominent components of the phosphomonoesters were glucose 6-phosphate, alpha-glycerol phosphate and AMP. In conclusion, of the various phosphorus metabolites that can be measured by 31P NMR, only one group, the phosphomonoesters, was predictive of functional recovery.
高能磷酸盐耗竭、无机磷酸盐蓄积和细胞内酸中毒均被认为是从可逆性缺血损伤转变为不可逆性缺血损伤过程中的重要事件。为了评估每个变量是否可预测再灌注时的功能恢复情况，使用31P核磁共振在离体等容大鼠心脏中对这些变量进行了测量。给灌注心脏进行10、12或40分钟的常温缺血，随后再灌注40分钟。然后将心脏冷冻钳夹，以便通过核磁共振和离子色谱对磷酸盐代谢物进行进一步分析。每隔2分钟通过31P核磁共振波谱法测量高能磷酸盐、无机磷酸盐、磷酸单酯和pH值。同时监测心率和心室内压。所有经历10分钟缺血的心脏以及40%经历12分钟缺血的心脏均表现出良好的功能恢复。其余经历12分钟缺血的心脏在再灌注时发生挛缩，几乎没有功能恢复。再灌注前测量的细胞内pH值、三磷酸腺苷（ATP）和无机磷酸盐浓度并不能预测恢复程度。然而，在所有恢复不佳的心脏再灌注前均检测到磷酸单酯，但在机械恢复良好的心脏中未观察到。通过31P核磁共振和离子色谱对组织提取物进行分析表明，磷酸单酯最主要的成分是6-磷酸葡萄糖、α-甘油磷酸和一磷酸腺苷（AMP）。总之，在可通过31P核磁共振测量的各种磷代谢物中，只有一组，即磷酸单酯，可预测功能恢复情况。
