肝虚血障害に対するCa²⁺拮抗剤(塩酸ジルチアゼム)の防御効果ならびに肝移植への応用に関する実験的研究

Abstract

The purpose of this study was to investigate the protective effects of a calcium channel blocker, Diltiazem (DZ), on ischemic liver damage. Adult mongrel dogs were used as experimental animals. Hepatic ischemia was induced by clamping the portal vein and the hepatic artery for 60 minutes with establishment of a porto-juglar bypass. The administration of DZ at a dose of 70 μg/kg intravenously before hepatic ischemia and thereafter via portal vein at a dose of 10 μg/kg/min well restored the hepatic blood flow (HBF : 92±5%) and arterial ketone body ratio (AKBR : 1.15±0.16) 1 hour after reperfusion compared with untreated controls (HBF : 61±7%, AKBR : 0.53±0.09). Furthermore, it was examined whether or not DZ might prevent primary non-function in liver transplantation. As the model of primary non-function, warm ischemically damaged liver for 20 minutes was transplanted orthotopically. In untreated animals, all five recipients died from massive bleeding caused by liver failure within 24 hours after hepatic grafting. On the other hand, when DZ was administered intravenously at a dose of 70 μg/kg to the donor just before inducing warm ischemia, and also to the recipient via portal vein at a dose of 10 μg/kg/min, three of six recipients (50%) could survive over 48 hours after grafting without liver failure. In conclusion, these results suggest that DZ has protective effects on liver ischemia and prevents primary non-function in liver transplantation.