Rooth P, Dawidson I, Diller K, Täljedal I B
Department of Surgery, University of Texas Health Science Center, Dallas 75235.
Transplantation. 1988 Feb;45(2):433-7. doi: 10.1097/00007890-198802000-00038.
Fluorescence microscopy was used to examine the effect of cyclosporine (CsA) infusion on renal subcapsular (cortical) blood flow in 53 living mice, using FITC-dextran (MW: 156,000) as a fluorescent marker. CsA (8-19 mg/kg body weight) given i.v. for 1 min induced complete inhibition of blood flow. A complete standstill of flow was also obtained during a continuous infusion with a rate of 0.8-2 mg/kg/min. With lower infusion rates (0.15-0.23 mg/kg/min), blood flow was partially impaired. In all experiments, the decrease in flow occurred after a 15-25 min delay, suggesting a CsA metabolite or exhaustion of a protective mechanism as the causative agent. Pretreatment with an alpha-blocking agent, phentolamine (1.0 mg/kg), did not prevent the CsA-induced inhibition of blood flow. In contrast, pretreatment with a calcium antagonist, verapamil (0.3-0.4 mg/kg), prevented the impairment of blood flow at low (0.15-0.23 mg/kg/min), and partially at higher (0.8-2.4 mg/kg/min) rates of CsA infusion. Clinical studies are warranted to explore the role of calcium antagonists in the prevention of posttransplant acute cyclosporine-induced nephrotoxicity.
利用荧光显微镜，以异硫氰酸荧光素标记的葡聚糖（分子量：156,000）作为荧光标记物，研究了环孢素（CsA）输注对53只活体小鼠肾被膜下（皮质）血流的影响。静脉注射8 - 19毫克/千克体重的CsA持续1分钟可导致血流完全抑制。以0.8 - 2毫克/千克/分钟的速率持续输注时也会出现血流完全停滞。当输注速率较低（0.15 - 0.23毫克/千克/分钟）时，血流会部分受损。在所有实验中，血流减少在延迟15 - 25分钟后出现，提示CsA代谢产物或保护机制耗竭是致病因素。用α阻滞剂酚妥拉明（1.0毫克/千克）预处理不能预防CsA诱导的血流抑制。相反，用钙拮抗剂维拉帕米（0.3 - 0.4毫克/千克）预处理可预防低输注速率（0.15 - 0.23毫克/千克/分钟）时的血流受损，在较高输注速率（0.8 - 2.4毫克/千克/分钟）时可部分预防。有必要进行临床研究以探讨钙拮抗剂在预防移植后急性环孢素诱导的肾毒性中的作用。
