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The effect of nifedipine, a calcium channel blocker, on liver ischemia in dogs

The Japanese journal of surgery volume 18, pages 84–92 (1988)Cite this article

Abstract

This study was undertaken in order to determine whether the administration of nifedipine, a calcium channel blocker, could protect the liver from ischemic damage and to investigate its effect on the hepatic cellular energy status and cardio-vascular system after 60 minutes of hepatic ischemia in dogs. The ischemia was induced by temporarily clamping the portal vein and hepatic artery. One group of animals (n=17) received nifedipine (5 μg/kg body weight) intravenously 15 minutes before the induction of liver ischemia, which was continued at a dose of 0.2 μg/kg body weight/min throughout the ischemic period, and for an additional 30 minutes afterwards. Control dogs (n=16) were not given nifedipine and survival was observed over seven days. The survival rate was 83 per cent in the nifedipine treated animals and 0 per cent in the control animals. Serum glutamic oxaloacetic transaminase levels were greatly increased following ischemia, and they were significantly lowered with the nifedipine treatment. The hepatic energy charge decreased remarkably during the hepatic ischemia, however it increased gradually after declamping but did not returned to its preoperative value in either group until one hour later and then it was higher in the nifedipine treated animals than in the control animals. Cardiac index and portal venous blood flow ratio remained higher in the nifedipine treated animals than in the control animals, after the ischemic period. These results suggest that nifedipine may have a powerful cytoprotective effect and that the period of warm hepatic ischemia could be prolonged with its use.

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References

  1. Nagao T, Inoue S, Mizuta T, Saito H, Kawano N, Morioka Y. One hundred hepatic resections. Indications and operative results. Ann Surg 1985; 202: 42–49.

    PubMed  CAS  Google Scholar 

  2. Pringle JH. Notes on the arrest of hepatic hemorrhage due to trauma. Ann Surg 1908; 48: 541–549.

    PubMed  CAS  Google Scholar 

  3. Farber JL. Minirevies. The role of calcium in cell death. Life Science 1981; 29: 1289–1295.

    CAS  Article  Google Scholar 

  4. Henry PD, Shuchleib R, Borda LJ, Roberts R, Williamson JR, Sobel BE. Effects of nifedipine on myocarcial perfusion and ischemic injury in dogs. Cir Res 1978; 43: 372–380.

    CAS  Google Scholar 

  5. Nagao T, Matlib MA, Franklin D, Millard RW, Schwartz A. Effects of diltiazem, a calcium antagonist, on regional myocardial function and mitochondria after brief coronary occlusion. J Mol Cel Cardiol 1980; 12: 29–43.

    CAS  Article  Google Scholar 

  6. Clark ER, Ferguson TB, West PN, Schchleib RC, Henry PD. Pharmacological preservation of the ischemic heart. Ann Thoracic Surg 1977; 24: 307–314.

    CAS  Article  Google Scholar 

  7. Hoffmeister F, Kazda S, Krause HP. Influence of nimodipine (Bay e 9736) on the postischemic changes of brain function. In: Cerebral blood flow and metabolism. Acta Neurol Scand 1979; 60 (Suppl. 72): 358–363.

    Google Scholar 

  8. Hertle L, Garthoff B. Calcium channel blocker nisoldipine limits ischemic damage in rat kidney. J Urology 1985; 134: 1251–1254.

    CAS  Google Scholar 

  9. Piggioli J, Mauger JP, Guesdon F, Claret M. A regulatory calcium-binding site for calcium channel in isolated rat hepatocytes. J Biol Chem 1985; 260: 3289–3294.

    Google Scholar 

  10. Taylor WM, van de Pol E, van Helden DF, Reinhart PH, Bygrave FL. Effect of depolarizing concentrations of potassium on calcium uptake and metabolism in rat liver. FEBS 1985; 183: 70–74.

    CAS  Article  Google Scholar 

  11. Lefer AM. Hepatoprotective actions of calcium channel blockers. In Keppler D, editor: Mechanisms of hepatocyte injury and death. England, 1984, MTP Press, 361–368.

    Google Scholar 

  12. Payne RB, Little AJ, Williams RB, Milner JR. Interpretation of serum calcium in patients with abnormal serum proteins. Br Med J 1973; 15: 643–646.

    Article  Google Scholar 

  13. Raffucci FL. The effects of temporary occlusion of the afferent hepatic circulation in dogs. Surgery 1953; 33: 342–351.

    PubMed  CAS  Google Scholar 

  14. Jolly PC, Foster JH. Hepatic inflow stasis. Surgery 1963; 54: 45–55.

    Google Scholar 

  15. Hines JR, Roncoroni M. Acute hepatic ischemia in dogs. Surg Gynecol Obstet 1956; 96: 689–694.

    Google Scholar 

  16. Farkough FF, Daniel AM, Beaudoin JG, MacLean LD. Predictive value of liver biochemistry in acute hepatic ischemia. Surg Gynecol Obstet 1971; 111: 832–838.

    Google Scholar 

  17. Toledo-Pereyra LH. Role of activated carbon hemoperfusion in the recovery of livers exposed to ischemic damage. Arch Surg 1985; 120: 462–465.

    PubMed  CAS  Google Scholar 

  18. Battersby C, Hickman R, Saunders ST, Terblanche J. Liver function in the pig: 1. the effects of 30 minutes' normothermic ischaemia. Br J Surg 1974; 61: 27–32.

    PubMed  CAS  Google Scholar 

  19. Naordlinger B, Douvin D, Javaudin L, Bloch P, Aranda A, Boschat M, Huguet C. An experimental study of survival after two hours of normothermic hepatic ischemia. Surg Gynecol Obstet 1980; 150: 859–864.

    Google Scholar 

  20. McMaster P, Medd R. Total hepatic ischemia in the rhesus monkey. Br J Surg 1977; 64: 819–821.

    PubMed  CAS  Google Scholar 

  21. Barnett WO, Griffin JC, Morris L. Studies concerning hepatic pH changes and survival following temporary afferent vascular arrest to the liver. Surgery 1958; 43: 572–577.

    PubMed  CAS  Google Scholar 

  22. Brunschwig A. Observations on the surgical physiology of the human liver partinent to radical partial hepatectomy for neoplasm. Cancer 1955; 8: 459–466.

    PubMed  CAS  Article  Google Scholar 

  23. Diluzio NR, Olcay I, Holper K, Drapanas T, Trejo R. The relationship of reticuloendothelial dysfunction and endotoxemia to survival after hepatic ischemia injury in the baboon. Cir Shock 1975; 2: 77–89.

    Google Scholar 

  24. Joseph WL, Fonkalsrud EW, Longmire WP. Vasodepressive effects of the venous effluent following canine liver allotransplantation. J Surg Res 1968; 8: 367–372.

    PubMed  CAS  Article  Google Scholar 

  25. Drapanas T, Becker DR, Alfano GS, Potter WH, Stewart JD. Some effects of interrupting hepatic blood flow. Ann Surg 1955; 142: 831–835.

    PubMed  CAS  Article  Google Scholar 

  26. Hall RR. Hyperkalemia following temporary occlusion of the portal vein and hepatic artery. Br J Surg 1972; 59: 125–128.

    PubMed  CAS  Google Scholar 

  27. Goodall RGW, Hyndman WWB, Gurd FN. Studies on hypothermia in abdominal surgery. II. Occlusion of the vascular inflow to the liver. A M A Arch Surg 1957; 75: 1011–1019.

    Google Scholar 

  28. Hirasawa H, Chaudry IH, Baue AE. Improved hepatic function and survival with adenosine triphosphate-magnesium chloride after hepatic ischemia. Surgery 1978; 83: 655–662.

    PubMed  CAS  Google Scholar 

  29. Sikujara O, Monden M, Toyoshima K, Okamura J, Kosaki G. Cytoprotective effect of prostaglandin I2 on ischemia-induced hepatic cell injury. Transplantation 1983; 36: 238–243.

    PubMed  CAS  Google Scholar 

  30. Marubayashi S, Dohi K, Haruo E, Hayashi K, Kawasaki T. Preservation of ischemic rat liver mitochondrial function and liver viability with Co-Q10. Surgery 1982; 91: 631–637.

    PubMed  CAS  Google Scholar 

  31. Marubayashi S, Dohi K, Ochi K, Kawasaki T. Role of free radicals in ischemic rat liver cell injury: Prevention of damage by alpha-tocopherol administration. Surgery 1986; 99: 184–192.

    PubMed  CAS  Google Scholar 

  32. Delpin EAS, Figueroa I, Lopez R, Vazquez J. Protective effect of steroid on liver ischemia. Am Surgeon 1975; 41: 683–695.

    Google Scholar 

  33. Nordstrom G, Seeman T, Hasselgren PO. Beneficial effect of allopurinol in liver ischemia. Surgery 1984; 97: 679–684.

    Google Scholar 

  34. Farkough EF, Daniel AM, MacLean LD. The effect of collateral circulation on survival in liver ischemia. J Surg Res 1971; 11: 130–134.

    Article  Google Scholar 

  35. Hayase S, Hirakawa C, Hosokawa Y, Mori M, Ito H, Kondo Y, Hiei K, Sakano S. Basic and clinical studies on Bay a 1040 with special reference to its influence on the coronary, systemic resistance and capacitance blood vessels. Jap Circ J 1971; 38: 903–914.

    Google Scholar 

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Affiliations

  1. First Surgical Department, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113, Tokyo, Japan

    Fuyo Yoshimi MD, Masahiro Ishimaru, Motohide Sodeyama, Takeshi Nagao, Nobuhiro Kawano & Yasuhiko Morioka

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  1. Fuyo Yoshimi MD
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  2. Masahiro Ishimaru
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  3. Motohide Sodeyama
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  4. Takeshi Nagao
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  5. Nobuhiro Kawano
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  6. Yasuhiko Morioka
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Yoshimi, F., Ishimaru, M., Sodeyama, M. et al. The effect of nifedipine, a calcium channel blocker, on liver ischemia in dogs. The Japanese Journal of Surgery 18, 84–92 (1988). https://doi.org/10.1007/BF02470851

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  • DOI: https://doi.org/10.1007/BF02470851

Key Words

  • liver ischemia
  • cyto-protection
  • nifedipine