Bretan P N, Baldwin N, Martinez A, Stowe N, Scarpa A, Easley K, Erturk E, Jackson C, Pestana J, Novick A C
Department of Urology, Case Western Reserve University, Cleveland, Ohio.
Urol Res. 1991;19(2):73-80. doi: 10.1007/BF00368180.
A number of new intracellular renal flush solutions have been found to be more efficacious than Collins-2 (C-2) solution in extending organ viability during simple cold storage. However, the mechanism of action of these solutions remains poorly understood. To delineate better underlying intracellular mechanisms, we studied a modified, simple, hypothermic, intracellular (340 mOsm/kg) flush solution (PB-2). The development of PB-2 solution is based on the ability of some of its individual components to minimize ischemic adenine nucleotide (AN) catabolism and endothelial post "reperfusion injury." Preliminary results in 10 canine autorenal transplants show a significant (P less than 0.02) improvement in renal recovery and viability (recipient posttransplant inulin clearance and survival) after 50 h of cold storage compared with 10 canine kidneys similarly preserved using conventional C-2 flush solution. High performance liquid chromotography (HPLC) studies show a significant (P less than 0.01) loss of AN using C-2, while PB-2 was associated with regeneration of AN within 45 min of reperfusion. Magnetic resonance spectroscopy using phosphorus 31 (31P-MRS) showed more high energy phosphorus metabolites (phosphomonoester and nicotinamide-adenine-dinucleotide phosphate: P less than 0.001) at 50 h cold storage using PB-2 compared with C-2. Electron micrographs (EM) revealed normal microcapillary morphology for the PB-2 group; however, moderate vascular red and white blood cell clumping was observed in the C-2 group. Characterization of the basic preservation mechanisms by HPLC, 31P-MRS, and EM studies indicates that PB-2 solution enhances renal preservation by diminution of both reperfusion injury and the loss of intracellular high energy metabolites that are necessary for viability.
已发现多种新型细胞内肾冲洗液在简单冷藏期间延长器官存活能力方面比柯林斯 - 2(C - 2)溶液更有效。然而,这些溶液的作用机制仍知之甚少。为了更好地描述潜在的细胞内机制,我们研究了一种改良的、简单的、低温的、细胞内(340 mOsm/kg)冲洗液(PB - 2)。PB - 2溶液的研发基于其某些成分将缺血性腺嘌呤核苷酸(AN)分解代谢和内皮“再灌注损伤”降至最低的能力。10例犬自体肾移植的初步结果显示,与使用传统C - 2冲洗液同样保存的10个犬肾相比,冷藏50小时后,肾恢复和存活能力(移植后受体菊粉清除率和存活率)有显著(P小于0.02)改善。高效液相色谱(HPLC)研究显示,使用C - 2时AN有显著(P小于0.01)损失,而PB - 2与再灌注后45分钟内AN的再生有关。使用磷31的磁共振波谱(31P - MRS)显示,与C - 2相比,使用PB - 2冷藏50小时时具有更多高能磷代谢物(磷酸单酯和烟酰胺 - 腺嘌呤 - 二核苷酸磷酸:P小于0.001)。电子显微镜照片(EM)显示PB - 2组微毛细血管形态正常;然而,在C - 2组中观察到中度血管内红细胞和白细胞聚集。通过HPLC、31P - MRS和EM研究对基本保存机制的表征表明,PB - 2溶液通过减少再灌注损伤和细胞内维持存活所必需的高能代谢物的损失来增强肾脏保存。