During liver ischemia, the decrease in mitochondrial energy causes cellular damage that is aggravated after reperfusion. This injury can trigger a systemic inflammatory syndrome, also producing remote organ damage. Several substances have been employed to decrease this inflammatory response during liver transplantation, liver resections, and hypovolemic shock. The aim of this study was to evaluate the effects of hypertonic saline solution and the best timing of administration to prevent organ injury during experimental liver ischemia/reperfusion.
Rats underwent 1 hr of warm liver ischemia followed by reperfusion. Eighty-four rats were allocated into 6 groups: sham group, control of ischemia group (C), pre-ischemia treated NaCl 0.9% (ISS) and NaCl 7.5% (HTS) groups, pre-reperfusion ISS, and HTS groups. Blood and tissue samples were collected 4 hr after reperfusion.
HTS showed beneficial effects in prevention of liver ischemia/reperfusion injury. HTS groups developed increases in AST and ALT levels that were significantly less than ISS groups; however, the HTS pre-reperfusion group showed levels significantly less than the HTS pre-ischemia group. No differences in IL-6 and IL-10 levels were observed. A significant decrease in mitochondrial dysfunction as well as hepatic edema was observed in the HTS pre-reperfusion group. Pulmonary vascular permeability was significantly less in the pre-reperfusion HTS group compared to the ISS group. No differences in myeloperoxidase activity were observed. The liver histologic score was significantly less in the pre-reperfusion HTS group compared to the pre-ischemia HTS group.
HTS ameliorated local and systemic injuries in experimental liver ischemia/reperfusion. Infusion of HTS in the pre-reperfusion period may be an important adjunct to accomplish the best results.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Surgery
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Protection of the ischemic liver by donor pre-treatment before transplantation.Am J Surg. 1975; 129: 513-517
- Effect of total hepatic vascular exclusion during liver resection on hepatic ultrastructure.Liver Transpl Surg. 1996; 2: 461-467
- Hypertonic saline improves tissue oxygenation and reduces systemic and pulmonary inflammatory response caused by hemorrhagic shock.J Trauma. 2003; 54: 1137-1145
- Influence of warm ischemia time on initial graft function in human liver transplantation.Transplant Proc. 1997; 29: 3458-3459
- Organ preservation.Surg Clin North Am. 1986; 66: 617-632
- The role of calcium ions and calcium channel entry blockers in experimental ischemia/reperfusion induced liver injury.Ann Surg. 1991; 213: 137-142
- Modulation of mitochondrial calcium management attenuates hepatic warm ischemia/reperfusion injury.Liver Transpl. 2005; 11: 663-668
- [Is the mitochondrial respiratory activity a good parameter for hepatic ischemia and reperfusion injury?].Arq Gastroenterol. 2005; 42: 89-94
- 2-APB protects against liver ischemia/reperfusion injury by reducing cellular and mitochondrial calcium uptake.Am J Physiol Gastrointest Liver Physiol. 2007; 293: 623-630
- Role of neutrophils during the first 24 hours after liver ischemia and reperfusion injury.Transplant Proc. 1994; 26: 3695-3700
- Role of cytokines and cytokine-producing cells in reperfusion injury to the liver.Semin Liver Dis. 1999; 19: 171-187
- Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury.Hepatology. 2000; 32: 169-173
- Protective effect of N-2 mercaptopropionylglycine on rats and dogs liver during ischemia/reperfusion process.Arq Gastroenterol. 2003; 40: 177-180
- Hypertonic saline resuscitation decreases susceptibility to sepsis after hemorrhagic shock.J Trauma. 1997; 42: 602-606
- Immunomodulatory effects of hypertonic resuscitation on the development of lung inflammation following hemorrhagic shock.J Immunol. 1998; 161: 6288-6296
- Topical hepatic hypothermia attenuates pulmonary injury after hepatic ischemia and reperfusion.J Am Coll Surg. 2000; 191: 650-656
- Treatment of refractory hypovolaemic shock by 7.5% sodium chloride injections.Lancet. 1980; 2: 1002-1004
- Hyperosmotic NaCl and severe hemorrhagic shock.Am J Physiol. 1980; 239: 664-673
- Small volume hypertonic resuscitation of circulatory shock.Clinics. 2005; 60: 159-172
- Treatment of resistant intracranial hypertension with hypertonic saline. Report of two cases.J Neurosurg. 1988; 68: 478-481
- Prehospital hypertonic saline/dextran infusion for post-traumatic hypotension. The U.S.A. Multicenter Trial.Ann Surg. 1991; 213: 482-491
- Hypertonic preconditioning prevents hepatocellular injury following ischemia/reperfusion in mice: a role for interleukin 10.Hepatology. 2004; 40: 211-220
- Commission on Life Sciences, National Research Council. Guide for the care and use of laboratory animals.7th ed. National Academy Press, Washington (DC)1996
- Amelioration of liver injury by ischaemic preconditioning.Br J Surg. 1998; 85: 1636-1640
- [Protective effects of an inhibitor of glycoprotein IIb/IIIa in the hepatic and pulmonary disturbances secondary to ischemia and reperfusion injury of rat's liver.].Arq Gastroenterol. 2007; 44: 276-281
- Marginal hepatectomy in the rat: from anatomy to surgery.Ann Surg. 2006; 244: 89-98
- Hepatic damage during acute pancreatitis in the rat.Braz J Med Biol Res. 1997; 30: 947-953
- Oxidation and phosphorylation.in: Estabrook R.W. Pullman M.E. Methods in enzymology. Academic Press, New York1967
- A simple and rapid assay of oxidative phosphorylation.Nature. 1955; 175: 1120-1121
- Protein measurement with the Folin phenol reagent.J Biol Chem. 1951; 193: 265-275
- Immune complex induced pancreatitis: effect of BN 52021, a selective antagonist of platelet-activating factor.Prostaglandins. 1988; 35: 757-770
- Lung myeloperoxidase as a measure of pulmonary leukostasis in rabbits.J Appl Physiol. 1985; 59: 1978-1985
- Role of O2- in neutrophil recruitment into sites of dermal and pulmonary vasculitis.Free Radic Biol Med. 1990; 8: 163-172
- Ischemic preconditioning prevents apoptotic cell death and necrosis in early and intermediate phases of liver ischemia/reperfusion injury in rats.J Invest Surg. 2006; 19: 229-236
- Resuscitation from hemorrhagic shock: experimental model comparing normal saline, dextran, and hypertonic saline solutions.Crit Care Med. 2003; 31: 1915-1922
- Hypertonic saline improves intestinal mucosa barrier function and lung injury after trauma-hemorrhagic shock.Shock. 2002; 17: 496-501
- Chronicity of hyponatremia as a factor in experimental myelinolysis.Ann Neurol. 1984; 15: 544-547
- Management of hyponatremia.Am Fam Physician. 2004; 69: 2387-2394
- Hypertonic saline and the microcirculation.J Trauma. 2003; 54: S133-S140
- Attenuation of postischemic microvascular disturbances in striated muscle by hyperosmolar saline dextran.Am J Physiol. 1992; 263: H1411-H1416
- In vivo and in vitro modulation of intercellular adhesion molecule (ICAM)- 1 expression by hypertonicity.Shock. 2000; 14: 409-414
- Hepatic microsomal adenosine triphosphatase and mitochondrial function. Response to cold and warm ischemia.Arch Surg. 1987; 122: 813-816
- Local and systemic effects of hypertonic solution (NaCl 7.5%) in experimental acute pancreatitis.Pancreas. 2006; 32: 80-86
- P-selectin glycoprotein ligand-1 regulates chemokine-dependent leukocyte recruitment in colonic ischemia-reperfusion.Inflamm Res. 2007; 56: 452-458
- [Effects of hypertonic saline on expression of heme oxygenase enzyme-1 in hepatic ischemia/reperfusion injury rats].Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2006; 18: 5-8
- Pathophysiological role of endothelins in pulmonary microcirculatory disorders due to intestinal ischemia and reperfusion.J Surg Res. 1999; 87: 143-151
- Hypertonic saline resuscitation reduces neutrophil margination by suppressing neutrophil L selectin expression.J Trauma. 1998; 45: 7-12
- Synergistic induction of IL-10 by hypertonic saline solution and lipopolysaccharides in murine peritoneal macrophages.Surgery. 2001; 130: 157-165
Published online: December 11, 2009
Accepted: October 5, 2009
This work was supported by grant 05/04226-7 from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).
© 2010 Mosby, Inc. Published by Elsevier Inc. All rights reserved.