Segel L D, Follette D M, Baker J M, Rintoul T C
Division of Cardiothoracic Surgery, University of California School of Medicine, Davis 95616-8606, USA.
J Heart Lung Transplant. 1998 Feb;17(2):211-21.
These experiments were designed to evaluate the viability of large hearts after preservation by use of procedures that have shown good results with small animal hearts. Efficacy of novel long-term preservation protocols should be documented with a large animal model before such procedures can be adopted for clinical use. We studied the recovery of sheep hearts that were perfusion-preserved in media containing two different substrate mixtures and hearts stored without perfusion either in University of Wisconsin solution modified to maintain tissue adenosine triphosphate content or in Stanford solution.
Six groups of sheep hearts were studied: I, fresh nonpreserved controls; II, hearts perfusion-preserved at 11 degrees C for 24 hours by use of an oxygenated extracellular-type medium with pyruvate + glucose substrate; III, hearts preserved as for II but with aspartate + glutamate + glucose substrate; IV, hearts stored without perfusion at 3 degrees C for 24 hours in University of Wisconsin solution containing 2,3-butanedione monoxime 30 mmol/L, CaCl2 1 mmol/L, and fresh reduced glutathione 3 mmol/L; V, hearts stored without perfusion at 3 degrees C for 4 hours in Stanford solution; VI, hearts preserved as for II but without perfusion. Recovery was measured for 6 hours in a Langendorff model, perfused with an erythrocyte + albumin medium.
Hearts that were perfusion-preserved with both substrate mixtures and hearts stored in modified University of Wisconsin solution recovered function that was not significantly different from control subjects. Hearts stored in Stanford medium did not recover as well as did groups II, III, and IV. Left ventricular pressure and peak rate of left ventricular relaxation of the Stanford group were lower, and left ventricular enddiastolic pressure was higher, than those values for controls (repeated measures analysis of variance; Dunnett's procedure). The group VI hearts did not recover function at all.
The results suggest that large hearts preserved with medium containing either aspartate + glutamate + glucose or pyruvate + glucose have comparable recovery after long-term perfusion preservation. Aspartate + glutamate may offer advantages for clinical use because of their lower production of lactate and better chemical stability compared with pyruvate. Static storage in modified University of Wisconsin solution also produced viable hearts with recovery comparable to perfusion-preserved aspartate + glutamate + glucose hearts. Tests of these preservation media and procedures with large transplanted hearts are warranted.
这些实验旨在通过使用已在小动物心脏上显示出良好效果的方法来评估大型心脏保存后的活力。在将新的长期保存方案应用于临床之前，应使用大型动物模型记录其有效性。我们研究了在含有两种不同底物混合物的培养基中进行灌注保存的绵羊心脏，以及在改良以维持组织三磷酸腺苷含量的威斯康星大学溶液或斯坦福溶液中无灌注保存的心脏的恢复情况。
研究了六组绵羊心脏：I组，新鲜未保存的对照组；II组，使用含丙酮酸+葡萄糖底物的氧合细胞外型培养基在11℃下灌注保存24小时的心脏；III组，与II组相同，但使用天冬氨酸+谷氨酸+葡萄糖底物保存的心脏；IV组，在含有30 mmol/L 2,3-丁二酮单肟、1 mmol/L氯化钙和3 mmol/L新鲜还原型谷胱甘肽的威斯康星大学溶液中于3℃下无灌注保存24小时的心脏；V组，在斯坦福溶液中于3℃下无灌注保存4小时的心脏；VI组，与II组相同但无灌注保存的心脏。在Langendorff模型中用红细胞+白蛋白培养基灌注6小时来测量恢复情况。
用两种底物混合物进行灌注保存的心脏以及在改良的威斯康星大学溶液中保存的心脏恢复的功能与对照组无显著差异。保存在斯坦福培养基中的心脏恢复情况不如II、III和IV组。斯坦福组的左心室压力和左心室舒张峰值速率较低，左心室舒张末期压力高于对照组（重复测量方差分析；Dunnett法）。VI组心脏完全没有恢复功能。
结果表明，用含天冬氨酸+谷氨酸+葡萄糖或丙酮酸+葡萄糖的培养基保存的大型心脏在长期灌注保存后具有相当的恢复情况。天冬氨酸+谷氨酸可能因其与丙酮酸相比乳酸生成量较低且化学稳定性更好而在临床应用中具有优势。在改良的威斯康星大学溶液中静态保存也能产生具有与灌注保存的天冬氨酸+谷氨酸+葡萄糖心脏相当恢复情况的有活力的心脏。有必要对这些保存培养基和方法在大型移植心脏上进行测试。
