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Erschienen in: World Journal of Surgery 9/2009

01.09.2009

Ischemic Preconditioning Confers Antiapoptotic Protection During Major Hepatectomies Performed Under Combined Inflow and Outflow Exclusion of the Liver. A Randomized Clinical Trial

verfasst von: Nikolaos Arkadopoulos, Georgia Kostopanagiotou, Kassiani Theodoraki, Charalambos Farantos, Theodosios Theodosopoulos, Vaia Stafyla, John Vassiliou, Dionyssios Voros, Agathi Pafiti, Vassilios Smyrniotis

Erschienen in: World Journal of Surgery | Ausgabe 9/2009

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Abstract

Background

Extensive experimental studies and a few clinical series have shown that ischemic preconditioning (IPC) attenuates oxidative ischemia/reperfusion (I/R) injuries in liver resections performed under inflow vascular control. Selective hepatic vascular exclusion (SHVE) employed during hepatectomies completely deprives the liver of blood flow, as it entails simultaneous clamping of the portal triad and the main hepatic veins. The aim of the present study was to identify whether IPC can also protect hepatocytes during liver resections performed under SHVE.

Methods

Patients undergoing major liver resection were randomly assigned to have either only SHVE (control group, n = 43) or SHVE combined with IPC—10 min of ischemia followed by 15 min of reperfusion before SHVE was applied (IPC group, n = 41).

Results

The two groups were comparable with regard to age, liver resection volume, blood loss and transfusions, warm ischemic time, and total operative time. In liver remnant biopsies obtained 60 min post-reperfusion, IPC patients had significantly fewer cells stained positive by TUNEL compared to controls (19% ± 8% versus 45% ± 12%; p < 0.05). Also IPC patients had attenuated hepatocyte necrosis, systemic inflammatory response, and oxidative stress as manifested by lower postoperative peak values of aspartate transaminase, interleukin-6, interleukin-8, and malondialdehyde compared to controls. Morbidity was similar for the two groups, as were duration of intensive care unit stay and extent of total hospital stay.

Conclusions

In major hepatectomies performed under SHVE, ischemic preconditioning appears to attenuate apoptotic response of the liver remnant, possibly through alteration of inflammatory and oxidative pathways.
Literatur
1.
Zurück zum Zitat Kooby DA, Stockman J, Ben-Porat L et al (2003) Influence of transfusions on perioperative and long-term outcome in patients following hepatic resection for colorectal metastases. Ann Surg 237:860–870PubMedCrossRef Kooby DA, Stockman J, Ben-Porat L et al (2003) Influence of transfusions on perioperative and long-term outcome in patients following hepatic resection for colorectal metastases. Ann Surg 237:860–870PubMedCrossRef
2.
Zurück zum Zitat Smyrniotis V, Farantos Ch, Kostopanagiotou G et al (2005) Vascular control during hepatectomy: review of methods and results. World J Surg 29:1384–1396PubMedCrossRef Smyrniotis V, Farantos Ch, Kostopanagiotou G et al (2005) Vascular control during hepatectomy: review of methods and results. World J Surg 29:1384–1396PubMedCrossRef
3.
Zurück zum Zitat Belghiti J, Noun R, Malafosse R et al (1999) Continuous versus intermittent portal triad clamping for liver resection: a controlled study. Ann Surg 229:369–375PubMedCrossRef Belghiti J, Noun R, Malafosse R et al (1999) Continuous versus intermittent portal triad clamping for liver resection: a controlled study. Ann Surg 229:369–375PubMedCrossRef
4.
Zurück zum Zitat Smyrniotis VE, Kostopanagiotou GG, Lolis E et al (2003) Effects of hepatovenous back flow on ischemia–reperfusion injuries in liver resections with the Pringle maneuver. J Am Coll Surg 197:949–954PubMedCrossRef Smyrniotis VE, Kostopanagiotou GG, Lolis E et al (2003) Effects of hepatovenous back flow on ischemia–reperfusion injuries in liver resections with the Pringle maneuver. J Am Coll Surg 197:949–954PubMedCrossRef
5.
Zurück zum Zitat Yoshizumi T, Yanaga K, Soejima Y et al (1998) Amelioration of liver injury by ischemic preconditioning. Br J Surg 85:1636–1640PubMedCrossRef Yoshizumi T, Yanaga K, Soejima Y et al (1998) Amelioration of liver injury by ischemic preconditioning. Br J Surg 85:1636–1640PubMedCrossRef
6.
Zurück zum Zitat Carini R, Albano E (2003) Recent insights on the mechanisms of liver preconditioning. Gastroenterology 125:1480–1491PubMedCrossRef Carini R, Albano E (2003) Recent insights on the mechanisms of liver preconditioning. Gastroenterology 125:1480–1491PubMedCrossRef
7.
Zurück zum Zitat Wang NP, Bufkin BL, Nakamura M et al (1999) Ischemic preconditioning reduces neutrophil accumulation and myocardial apoptosis. Ann Thorac Surg 67:1689–1695PubMedCrossRef Wang NP, Bufkin BL, Nakamura M et al (1999) Ischemic preconditioning reduces neutrophil accumulation and myocardial apoptosis. Ann Thorac Surg 67:1689–1695PubMedCrossRef
8.
Zurück zum Zitat Glazier SS, O’Rourke DM, Graham DL et al (1994) Induction of ischemic tolerance following brief local ischemia in rat brain. J Cereb Blood Flow Metab 14:545–553PubMed Glazier SS, O’Rourke DM, Graham DL et al (1994) Induction of ischemic tolerance following brief local ischemia in rat brain. J Cereb Blood Flow Metab 14:545–553PubMed
9.
Zurück zum Zitat Cavalieri B, Perelli MG, Aragno M et al (2002) Ischemic preconditioning attenuates the oxidant-dependent mechanisms of reperfusion cell damage and death in rat liver. Liver Transpl 8:990–999PubMedCrossRef Cavalieri B, Perelli MG, Aragno M et al (2002) Ischemic preconditioning attenuates the oxidant-dependent mechanisms of reperfusion cell damage and death in rat liver. Liver Transpl 8:990–999PubMedCrossRef
10.
Zurück zum Zitat Quireze C, de Souza Montero EF, Cubero Leitão RM et al (2006) Ischemic preconditioning prevents apoptotic cell death and necrosis in early and intermediate phases of liver ischemia–reperfusion injury in the rats. J Invest Surg 19:229–236PubMedCrossRef Quireze C, de Souza Montero EF, Cubero Leitão RM et al (2006) Ischemic preconditioning prevents apoptotic cell death and necrosis in early and intermediate phases of liver ischemia–reperfusion injury in the rats. J Invest Surg 19:229–236PubMedCrossRef
11.
Zurück zum Zitat Clavien PA, Yadav S, Sindram D et al (2000) Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans. Ann Surg 232:155–162PubMedCrossRef Clavien PA, Yadav S, Sindram D et al (2000) Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans. Ann Surg 232:155–162PubMedCrossRef
12.
Zurück zum Zitat Clavien PA, Selzner M, Rüdiger HA et al (2003) A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning. Ann Surg 238:843–852PubMedCrossRef Clavien PA, Selzner M, Rüdiger HA et al (2003) A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning. Ann Surg 238:843–852PubMedCrossRef
13.
Zurück zum Zitat Azoulay D, Lucidi V, Andreani P et al (2006) Ischemic preconditioning for major liver resection under vascular exclusion of the liver preserving caval flow: a randomized prospective study. J Am Coll Surg 202:203–211PubMedCrossRef Azoulay D, Lucidi V, Andreani P et al (2006) Ischemic preconditioning for major liver resection under vascular exclusion of the liver preserving caval flow: a randomized prospective study. J Am Coll Surg 202:203–211PubMedCrossRef
14.
Zurück zum Zitat Fukai M, Hayashi T, Yokota R et al (2005) Lipid peroxidation during ischemia depends on ischemia time in warm ischemia and reperfusion of rat liver. Free Radic Biol Med 38:1372–1381PubMedCrossRef Fukai M, Hayashi T, Yokota R et al (2005) Lipid peroxidation during ischemia depends on ischemia time in warm ischemia and reperfusion of rat liver. Free Radic Biol Med 38:1372–1381PubMedCrossRef
15.
Zurück zum Zitat Peralta C, Hotter G, Closa D et al (1997) Protective effect of preconditioning on the injury associated to hepatic ischemia–reperfusion in the rat: role of nitric oxide and adenosine. Hepatology 25:934–937PubMedCrossRef Peralta C, Hotter G, Closa D et al (1997) Protective effect of preconditioning on the injury associated to hepatic ischemia–reperfusion in the rat: role of nitric oxide and adenosine. Hepatology 25:934–937PubMedCrossRef
16.
Zurück zum Zitat Peralta C, Fernández L, Panés J et al (2001) Preconditioning protects against systemic disorders associated with hepatic ischemia–reperfusion through blockade of tumor necrosis factor–induced P-selectin up-regulation in the rat. Hepatology 33:100–113PubMedCrossRef Peralta C, Fernández L, Panés J et al (2001) Preconditioning protects against systemic disorders associated with hepatic ischemia–reperfusion through blockade of tumor necrosis factor–induced P-selectin up-regulation in the rat. Hepatology 33:100–113PubMedCrossRef
17.
Zurück zum Zitat Peralta C, Bartrons R, Riera L et al (2000) Hepatic preconditioning preserves energy metabolism during sustained ischemia. Am J Physiol Gastrointest Liver Physiol 279:G163–G171PubMed Peralta C, Bartrons R, Riera L et al (2000) Hepatic preconditioning preserves energy metabolism during sustained ischemia. Am J Physiol Gastrointest Liver Physiol 279:G163–G171PubMed
18.
Zurück zum Zitat Howell JG, Zibari GB, Brown MF et al (2000) Both ischemic and pharmacological preconditioning decrease hepatic leukocyte/endothelial cell interactions. Transplantation 69:300–303PubMedCrossRef Howell JG, Zibari GB, Brown MF et al (2000) Both ischemic and pharmacological preconditioning decrease hepatic leukocyte/endothelial cell interactions. Transplantation 69:300–303PubMedCrossRef
19.
Zurück zum Zitat Peralta C, Closa D, Xaus C et al (1998) Hepatic preconditioning in rats is defined by a balance of adenosine and xanthine. Hepatology 28:768–773PubMedCrossRef Peralta C, Closa D, Xaus C et al (1998) Hepatic preconditioning in rats is defined by a balance of adenosine and xanthine. Hepatology 28:768–773PubMedCrossRef
20.
Zurück zum Zitat Serafin A, Rosello-Catafau J, Prats N et al (2004) Ischemic preconditioning affects interleukin release in fatty livers of rats undergoing ischemia/reperfusion. Hepatology 39:688–698PubMedCrossRef Serafin A, Rosello-Catafau J, Prats N et al (2004) Ischemic preconditioning affects interleukin release in fatty livers of rats undergoing ischemia/reperfusion. Hepatology 39:688–698PubMedCrossRef
21.
Zurück zum Zitat Kim YI, Song KE, Ryeon HK et al (2002) Enhanced inflammatory cytokine production at ischemia/reperfusion in human liver resection. Hepatogastroenterology 49:1077–1082PubMed Kim YI, Song KE, Ryeon HK et al (2002) Enhanced inflammatory cytokine production at ischemia/reperfusion in human liver resection. Hepatogastroenterology 49:1077–1082PubMed
22.
Zurück zum Zitat Arai M, Thurman RG, Lemasters JJ (2001) Ischemic preconditioning of rat livers against cold storage-reperfusion injury: role of nonparenchymal cells and the phenomenon of heterologous preconditioning. Liver Transpl 7:292–299PubMedCrossRef Arai M, Thurman RG, Lemasters JJ (2001) Ischemic preconditioning of rat livers against cold storage-reperfusion injury: role of nonparenchymal cells and the phenomenon of heterologous preconditioning. Liver Transpl 7:292–299PubMedCrossRef
23.
Zurück zum Zitat Lee WY, Lee SM (2005) Ischemic preconditioning protects post-ischemic oxidative damage to mitochondria in rat liver. Shock 24:370–375PubMedCrossRef Lee WY, Lee SM (2005) Ischemic preconditioning protects post-ischemic oxidative damage to mitochondria in rat liver. Shock 24:370–375PubMedCrossRef
24.
Zurück zum Zitat Rudiger HA, Graf R, Clavien PA (2003) Sub-lethal oxidative stress triggers the protective effects of ischemic preconditioning in the mouse liver. J Hepatol 39:972–977PubMedCrossRef Rudiger HA, Graf R, Clavien PA (2003) Sub-lethal oxidative stress triggers the protective effects of ischemic preconditioning in the mouse liver. J Hepatol 39:972–977PubMedCrossRef
25.
Zurück zum Zitat Izuishi K, Tsung A, Hossain MA et al (2006) Ischemic preconditioning of the murine liver protects through the Akt kinase pathway. Hepatology 44:573–580PubMedCrossRef Izuishi K, Tsung A, Hossain MA et al (2006) Ischemic preconditioning of the murine liver protects through the Akt kinase pathway. Hepatology 44:573–580PubMedCrossRef
26.
Zurück zum Zitat Hu GH, Lu XS (2005) Effect of normothermic liver ischemic preconditioning on the expression of apoptosis-regulating genes C-jun and Bcl-XL in rats. World J Gastroenterol 11:2579–2582PubMed Hu GH, Lu XS (2005) Effect of normothermic liver ischemic preconditioning on the expression of apoptosis-regulating genes C-jun and Bcl-XL in rats. World J Gastroenterol 11:2579–2582PubMed
27.
Zurück zum Zitat Li SQ, Liang LJ, Huang JF et al (2004) Ischemic preconditioning protects liver from hepatectomy under hepatic inflow occlusion for hepatocellular carcinoma patients with cirrhosis. World J Gastroenterol 10:2580–2584PubMed Li SQ, Liang LJ, Huang JF et al (2004) Ischemic preconditioning protects liver from hepatectomy under hepatic inflow occlusion for hepatocellular carcinoma patients with cirrhosis. World J Gastroenterol 10:2580–2584PubMed
28.
Zurück zum Zitat Barrier A, Olaya N, Chiappini F et al (2005) Ischemic preconditioning modulates the expression of several genes, leading to overproduction of IL-1Ra, iNOS, and Bcl-2 in a human model of liver ischemia-reperfusion. FASEB J 19:1617–1626PubMedCrossRef Barrier A, Olaya N, Chiappini F et al (2005) Ischemic preconditioning modulates the expression of several genes, leading to overproduction of IL-1Ra, iNOS, and Bcl-2 in a human model of liver ischemia-reperfusion. FASEB J 19:1617–1626PubMedCrossRef
29.
Zurück zum Zitat Rudiger HA, Kang KJ, Sindram D et al (2002) Comparison of ischemic preconditioning and intermittent and continuous inflow occlusion in the murine liver. Ann Surg 235:400–407PubMedCrossRef Rudiger HA, Kang KJ, Sindram D et al (2002) Comparison of ischemic preconditioning and intermittent and continuous inflow occlusion in the murine liver. Ann Surg 235:400–407PubMedCrossRef
30.
Zurück zum Zitat Smyrniotis V, Kostopanagiotou G, Theodoraki K et al (2005) Ischemic preconditioning versus intermittent vascular inflow control during major liver resection in pigs. World J Surg 29:930–934PubMedCrossRef Smyrniotis V, Kostopanagiotou G, Theodoraki K et al (2005) Ischemic preconditioning versus intermittent vascular inflow control during major liver resection in pigs. World J Surg 29:930–934PubMedCrossRef
31.
Zurück zum Zitat Chouker A, Martignoni A, Schauer R et al (2005) Beneficial effects of ischemic preconditioning in patients undergoing hepatectomy: the role of neutrophilis. Arch Surg 140:129–136PubMedCrossRef Chouker A, Martignoni A, Schauer R et al (2005) Beneficial effects of ischemic preconditioning in patients undergoing hepatectomy: the role of neutrophilis. Arch Surg 140:129–136PubMedCrossRef
32.
Zurück zum Zitat Nuzzo G, Giuliante F, Vellone M et al (2004) Pedicle clamping with ischemic preconditioning in liver resection. Liver Transpl 10:S53–S57PubMedCrossRef Nuzzo G, Giuliante F, Vellone M et al (2004) Pedicle clamping with ischemic preconditioning in liver resection. Liver Transpl 10:S53–S57PubMedCrossRef
33.
Zurück zum Zitat Petrowsky H, McCormack L, Trujillo M et al (2006) A prospective, randomized, trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection. Ann Surg 244:921–930PubMedCrossRef Petrowsky H, McCormack L, Trujillo M et al (2006) A prospective, randomized, trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection. Ann Surg 244:921–930PubMedCrossRef
34.
Zurück zum Zitat Smyrniotis V, Theodoraki K, Arkadopoulos N et al (2006) Ischemic preconditioning versus intermittent vascular occlusion in liver resections under selective vascular exclusion: a prospective randomized study. Am J Surg 192:669–674PubMedCrossRef Smyrniotis V, Theodoraki K, Arkadopoulos N et al (2006) Ischemic preconditioning versus intermittent vascular occlusion in liver resections under selective vascular exclusion: a prospective randomized study. Am J Surg 192:669–674PubMedCrossRef
35.
Zurück zum Zitat McCurry KR, Campbell DA Jr, Scales WE et al (1993) Tumor necrosis factor, interleukin 6, and the acute phase response following hepatic ischemia/reperfusion. J Surg Res 55:49–54PubMedCrossRef McCurry KR, Campbell DA Jr, Scales WE et al (1993) Tumor necrosis factor, interleukin 6, and the acute phase response following hepatic ischemia/reperfusion. J Surg Res 55:49–54PubMedCrossRef
36.
Zurück zum Zitat Villarete LH, Remick DG (1997) Nitric oxide regulation of interleukin-8 gene expression. Shock 7:29–35PubMedCrossRef Villarete LH, Remick DG (1997) Nitric oxide regulation of interleukin-8 gene expression. Shock 7:29–35PubMedCrossRef
37.
Zurück zum Zitat Remick DG, Villarete L (1996) Regulation of cytokine gene expression by reactive oxygen and reactive nitrogen intermediates. J Leukoc Biol 59:471–475PubMed Remick DG, Villarete L (1996) Regulation of cytokine gene expression by reactive oxygen and reactive nitrogen intermediates. J Leukoc Biol 59:471–475PubMed
38.
Zurück zum Zitat Yamada T, Hisanaga M, Nakajima Y et al (1999) The serum interleukin 8 level reflects hepatic mitochondrial redox state in hyperthermochemohypoxic isolated liver perfusion with use of a venovenous bypass. Surgery 125:304–314PubMed Yamada T, Hisanaga M, Nakajima Y et al (1999) The serum interleukin 8 level reflects hepatic mitochondrial redox state in hyperthermochemohypoxic isolated liver perfusion with use of a venovenous bypass. Surgery 125:304–314PubMed
Metadaten
Titel
Ischemic Preconditioning Confers Antiapoptotic Protection During Major Hepatectomies Performed Under Combined Inflow and Outflow Exclusion of the Liver. A Randomized Clinical Trial
verfasst von
Nikolaos Arkadopoulos
Georgia Kostopanagiotou
Kassiani Theodoraki
Charalambos Farantos
Theodosios Theodosopoulos
Vaia Stafyla
John Vassiliou
Dionyssios Voros
Agathi Pafiti
Vassilios Smyrniotis
Publikationsdatum
01.09.2009
Verlag
Springer-Verlag
Erschienen in
World Journal of Surgery / Ausgabe 9/2009
Print ISSN: 0364-2313
Elektronische ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-009-0117-0

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