Segel L D, Follette D M
Department of Surgery, University of California School of Medicine, Davis 95616, USA.
J Heart Lung Transplant. 1998 Mar;17(3):299-305.
Previous work has suggested that recovery of cardiac function after long preservation periods is improved if a suitable exogenous substrate is provided. However, interpretation of existing data on the benefit of added substrate is complicated by differing preservation media and protocols studied, as well as differing models used to evaluate postpreservation recovery. These experiments were designed to evaluate glucose, pyruvate, aspartate, and glutamate as exogenous substrates for prolonged perfusion preservation of hearts with a rat heart model preserved with crystalloid medium and with function quantified in an isolated working heart preparation.
Cardiac function (n = 5/group) and tissue glycogen content (n = 5/group) were measured in fresh control rat hearts and four groups of hearts preserved for 24 hours in an extracellular-type cardioplegic medium containing 11 mmol/L glucose and either 20 mmol/L sodium aspartate, 20 mmol/L sodium glutamate, 20 mmol/L sodium pyruvate, or no other substrate. Postpreservation cardiac function was measured in an isolated working rat heart preparation for a 4-hour reperfusion period. Exogenous substrate consumption during preservation and tissue glycogen content at the end of preservation were measured with spectrophotometric assays.
All hearts in the aspartate- and glutamate-preserved groups functioned for the full 4-hour period with stroke work that was 50% to 60% of control. Hearts preserved with only glucose substrate had inconsistent recovery: two of five hearts in that group did not recover, whereas three recovered similar to the aspartate and glutamate groups. None of the pyruvate-preserved hearts recovered contractile function. There was no association between postpreservation tissue glycogen content and extent of cardiac function recovery.
Aspartate or glutamate plus glucose was the best substrate mixture among those tested for long-term perfusion preservation of hearts. These amino acids offer advantages over pyruvate because they produced better recovery of the hearts and because they are chemically more stable than pyruvate. Aspartate or glutamate plus glucose also produced better postpreservation function compared with glucose alone.
先前的研究表明，如果提供合适的外源性底物，长时间保存后心脏功能的恢复会得到改善。然而，由于所研究的保存介质和方案不同，以及用于评估保存后恢复的模型不同，对添加底物益处的现有数据的解释变得复杂。这些实验旨在评估葡萄糖、丙酮酸、天冬氨酸和谷氨酸作为外源性底物，用于在晶体介质中保存大鼠心脏的长时间灌注保存，并在离体工作心脏制备中对功能进行量化。
在新鲜对照大鼠心脏以及四组在含有11 mmol/L葡萄糖和20 mmol/L天冬氨酸钠、20 mmol/L谷氨酸钠、20 mmol/L丙酮酸钠或无其他底物的细胞外型心脏停搏液中保存24小时的心脏中，测量心脏功能（每组n = 5）和组织糖原含量（每组n = 5）。在离体工作大鼠心脏制备中测量保存后4小时再灌注期的心脏功能。通过分光光度法测定保存期间外源性底物的消耗以及保存结束时的组织糖原含量。
天冬氨酸和谷氨酸保存组的所有心脏在整个4小时期间均能发挥功能，每搏功为对照组的50%至60%。仅用葡萄糖底物保存的心脏恢复情况不一致：该组五只心脏中有两只未恢复，而三只恢复情况与天冬氨酸和谷氨酸组相似。丙酮酸钠保存的心脏均未恢复收缩功能。保存后组织糖原含量与心脏功能恢复程度之间无关联。
在测试的用于心脏长期灌注保存的底物混合物中，天冬氨酸或谷氨酸加葡萄糖是最佳的。与丙酮酸相比，这些氨基酸具有优势，因为它们能使心脏恢复得更好，并且在化学性质上比丙酮酸更稳定。与单独使用葡萄糖相比，天冬氨酸或谷氨酸加葡萄糖在保存后也能产生更好的功能。
