Cheng S, Ragsdale J R, Sasaki A W, Lee R G, Deveney C W, Pinson C W
Department of Surgery, Oregon Health Sciences University, Portland 97201.
J Surg Res. 1991 Jun;50(6):560-4. doi: 10.1016/0022-4804(91)90041-j.
Verapamil, a calcium channel blocker, improves myocardial preservation during cold cardioplegia and protects against renal damage during periods of warm and cold ischemia. To determine if verapamil could prevent ischemic damage to livers during and after cold storage, harvested rat livers were flushed with either University of Wisconsin (UW) solution or UW solution with 25 mg/liter verapamil. Twenty rats were used in each group. After 24 hr of storage at 4 degrees C, livers were perfused with oxygenated blood through the portal veins for 2 hr at 37 degrees C and pH 7.4. Liver enzymes, electrolytes, and perfusate flow rate were determined at 30-min intervals. At 90 min of perfusion, the verapamil group of livers had less elevation of AST (110 +/- 17 IU/liter vs 172 +/- 25 IU/liter, P less than 0.05), ALT (115 +/- 21 IU/liter vs 210 +/- 34 IU/liter, P less than 0.05), and LDH (962 +/- 170 IU/liter vs 1452 +/- 253 IU/liter, NS). Verapamil livers produced more bile than controls (6.9 +/- 1.9 microliters/g vs 2.3 +/- 1.7 microliter/g, P less than 0.05) and maintained a higher portal flow rate throughout the perfusion. Both groups showed similar reduction in liver weights after storage (3.9 +/- 0.9% vs 2.8 +/- 0.7%) and required the same amount of bicarbonate for correction of acidosis during perfusion (2.6 +/- 0.2 mM vs 2.8 +/- 0.2 mM). Light microscopic exam after perfusion showed hepatocyte damage in 30% of control livers, but 0% of verapamil livers. We conclude that verapamil-treated rat livers showed less damage and better function upon reperfusion after 24 hr of cold storage. This agent may be clinically useful as an additive to the UW preservation solution for livers.
维拉帕米是一种钙通道阻滞剂，可改善冷停搏期间的心肌保护作用，并在温暖和寒冷缺血期间预防肾脏损伤。为了确定维拉帕米是否能预防冷藏期间及之后肝脏的缺血性损伤，将收获的大鼠肝脏用威斯康星大学（UW）溶液或含25毫克/升维拉帕米的UW溶液冲洗。每组使用20只大鼠。在4℃储存24小时后，将肝脏在37℃、pH 7.4条件下通过门静脉用含氧血液灌注2小时。每隔30分钟测定肝酶、电解质和灌注液流速。灌注90分钟时，维拉帕米组肝脏的AST升高幅度较小（110±17国际单位/升对172±25国际单位/升，P<0.05），ALT（115±21国际单位/升对210±34国际单位/升，P<0.05）和LDH（962±170国际单位/升对1452±253国际单位/升，无显著性差异）。维拉帕米处理的肝脏产生的胆汁比对照组多（6.9±1.9微升/克对2.3±1.7微升/克，P<0.05），并且在整个灌注过程中保持较高的门静脉流速。两组在储存后肝脏重量的减轻相似（3.9±0.9%对2.8±0.7%），并且在灌注期间纠正酸中毒所需的碳酸氢盐量相同（2.6±0.2毫摩尔对2.8±0.2毫摩尔）。灌注后的光镜检查显示，30%的对照肝脏有肝细胞损伤，而维拉帕米处理的肝脏为0%。我们得出结论，维拉帕米处理的大鼠肝脏在冷储存24小时后再灌注时损伤较小且功能更好。这种药物作为UW肝脏保存溶液的添加剂可能具有临床应用价值。
