Abstract
Purpose
The purpose of the study is to evaluate the protective effects of Verapamil on hepatic ischemia–reperfusion injury in cirrhotic patients with HCC.
Method
A controlled study was performed on 86 consecutive patients with cirrhosis who underwent liver resection for suffering HCC. Thirty-nine patients were injected with Verapamil through the mesenteric vein before Pringle's maneuver to alleviate hepatic ischemia–reperfusion injury, while 47 patients were not.
Results
The serum AST, ALT, and total bilirubin on days 1 and 3 were markedly lower in the Verapamil group than that in the control group postoperatively (AST, P < 0.001 and P < 0.001; ALT, P < 0.001 and P = 0.042; TB, P = 0.037 and 0.049; respectively). The serum hyluronic acid on day 1 was also significantly lower in Verapamil group than that in the control group (P < 0.01), but no marked difference on days 3 and 7. Meanwhile, the levels of IL6 on days 1 and 3 were markedly lower in the Verapamil group than that in control group (P < 0.05 and P < 0.01, respectively. The new Clavien's classification of surgical complications showed marked severity in the control group than that in the Verapamil group (P = 0.021), especially in the grade I level (P = 0.045).
Conclusion
Verapamil may serve as protective agent for hepatic ischemia–reperfusion injury in cirrhotic patients with HCC. Therefore, Verapamil can be used for treatment of patients who are to undergo hepatectomy with occlusion of hepatic blood flow.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bolling SF, Schirmer WJ, Gott VL, Flaherty JT, Bulkley BH, Gardner TJ (1983) Enhanced myocardial protection with Verapamil prior to postischemic reflow. Surgery 94:283–290
Burke TJ, Arnold PE, Gordon JA, Bulger RE, Dobyan DC, Schrier RW (1984) Protective effect of intrarenal calcium membrane blockers before or after renal ischemia: functional, morphological, and mitochondrial studies. J Clin Invest 74:1830–1841. doi:10.1172/JCI111602
Stein HJ, Fayman MS, Oosthuizen MMJ, Hinder RA (1989) Verapamil improves survival of rat hyperemic island skin flaps. Surgery 106:617–622
Nauta RJ, Tsimoyiannis E, Uribe M, Walsh DB, Miller D, Butterfield A (1991) The role of calcium ions and calcium channel entry blockers in experimental ischemia reperfusion induced liver injury. Ann Surg 213:137–142. doi:10.1097/00000658-199102000-00008
Shinohara M, Kayashima K, Konomi K (1990) Protective effects of Verapamil on ischemia-induced hepatic damage in the rat. Eur Surg Res 22:256–262. doi:10.1159/000129110
Cheng S, Ragsdale JR, Sasaki AW, Lee RG, Deveney CW, Pinson CW (1991) Verapamil improves rat hepatic preservation with UW solution. J Surg Res 50:560–564. doi:10.1016/0022-4804(91)90041-J
Ar'Rajab A, Ahren B, Bengmark S (1991) Improved liver preservation for transplantation due to calcium channel blockade. Transplantation 51:965–967
Liang J, Yamaguchi Y, Matsumura F, Goto M, Akizuki E, Matsuda T, Okabe K, Ohshiro H, Ishihara K, Yamada S, Mori K, Ogawa M (2000) Calcium-channel blocker attenuates Kupffer cell production of cytokine-induced neutrophil chemoattractant following ischemia–reperfusion in rat liver. Dig Dis Sci 45:201–209. doi:10.1023/A:1005498402659
Erdogan O, Yildiz S, Basaran A, Demirbas A, Yesilkaya A (2001) Effect of intraportal Verapamil infusion on hepatic ischemia–reperfusion injury. Pol J Pharmacol 53:137–141
Martins JR, Passerotti CC, Maciel RM, Sampaio LO, Dietrich CP, Nader HB (2003) Practical determination of hyaluronan by a new noncompetitive fluorescence-based assay on serum of normal and cirrhotic patients. Anal Biochem 319:65–72. doi:10.1016/S0003-2697(03)00251-3
Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:1074–1085. doi:10.1097/01.sla.0000133083.54934.ae
Uchida M, Takemoto Y, Nagasue N, Dhar DK, Kohno H, Nakamura T (1994) Effect of Verapamil on hepatic reperfusion injury after prolonged ischemia in pigs. J Hepatol 21:217–223. doi:10.1016/S0168-8278(05)80398-8
Yagmurdur MC, Ozdemir A, Topaloglu S, Kilinc K, Ozenc A (2002) Effects of alpha tocopherol and Verapamil on liver and small bowel following mesenteric ischemia–reperfusion. Turk J Gastroenterol 13:40–46
Karwinski W, Garcia R, Helton WS (1996) Protective effects of the calcium channel blocker Verapamil on hepatic function following warm ischemia. J Surg Res 64:150–155. doi:10.1006/jsre.1996.0321
Konrad T, Beier K, Kusterer K, Juchem R, Usadel KH, Angermuller S (1997) The effect of Verapamil on mitochondrial calcium content in normoxic, hypoxic and reoxygenated rat liver. Histochem J 29:309–315. doi:10.1023/A:1026426615130
Konrad T, Bloechle C, Haller G, Broelsch CE, Usadel KH, Kusterer K (1995) Verapamil and flunarizine protect the isolated perfused rat liver against warm ischemia and reperfusion injury. Res Exp Med (Berl) 195:61–68. doi:10.1007/BF02576775
Umemura S, Nakamura S, Sugiura T, Tsuka Y, Fujitaka K, Yoshida S, Baden M, Iwasaka T (2006) The effect of Verapamil on the restoration of myocardial perfusion and functional recovery in patients with angiographic no-reflow after primary percutaneous coronary intervention. Nucl Med Commun 27:247–254. doi:10.1097/00006231-200603000-00007
Ishii K, Suita S, Sumimoto H (1990) Effect of Verapamil on conversion of xanthine dehydrogenase to oxidase in ischemic rat liver. Res Exp Med (Berl) 190:389–399. doi:10.1007/BF00000045
Xiong C, Hu H, wei W, Chen X, Wu Z (2000) Liver sinusoidal endothelial cell damage during normothermic ischemia and reperfusion of rat. Zhonghua Wai Ke Za Zhi 38:297–299
Heath DI, Cruickshank A, Imrie CW (1993) Role of IL-6 in mediating the acute phase protein response and potential as an early means of severity assessment in acute pancreatitis. Gut 34:41–45. doi:10.1136/gut.34.1.41
Schulter B, Konig B, Konig W (1991) Il-6 a potential mediator of lethal sepsis after major thermal trauma: evidence for increased production by peripheral blood mononuclear cells. J Trauma 31:1663–1670. doi:10.1097/00005373-199112000-00017
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Xia, F., Wang, S., Chen, M. et al. Protective effect of Verapamil on hepatic ischemia–reperfusion injury during hepatectomy in the cirrhotic patients with hepatocellular carcinoma. Langenbecks Arch Surg 394, 1041–1046 (2009). https://doi.org/10.1007/s00423-009-0491-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00423-009-0491-y