El pretratamiento con alopurinol disminuye la translocación bacteriana y atenúa los cambios morfológicos de la mucosa intestinal en un modelo de isquemia-reperfusión intestinal en ratas
Resumen
Objetivo. Evaluar el efecto protector contra la lesión por isquemia-reperfusión intestinal del pretratamiento con alopurinol en ratas.
Materiales y métodos. Se llevó a cabo un experimento controlado en animales. Un grupo de 10 ratas Wistar de características morfométricas comparables se mantuvo en bioterio bajo condiciones controladas por tres días. A cinco animales se les administró 50 mg/kg diarios de alopurinol por vía oral durante los tres días y, una dosis adicional, antes de inducir isquemia intestinal por ligadura quirúrgica durante 60 minutos seguida de 60 minutos de reperfusión. El otro grupo de cinco ratas no recibió el medicamento. Se hizo el análisis histológico de la mucosa intestinal al final del experimento por medio de la clasificación de Chou y se tomaron hemocultivos de la cavidad cardiaca.
Resultados. Se encontraron hemocultivos positivos en 20 % de los animales pretratados con alopurinol, en comparación con el 100 % de las ratas control (p<0,0001). Se evidenció lesión profunda en la mucosa intestinal en todos los casos. La administración previa a la injuria de alopurinol redujo significativamente la lesión por isquemia-reperfusión (p<0,001).
Conclusiones. La administración de alopurinol antes de la isquemia intestinal, reduce los cambios morfológicos ocasionados por isquemia-reperfusión. El efecto benéfico se demostró con el pretratamiento por tres días.
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https://doi.org/10.1055/s-2008-1040319
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https://doi.org/10.1016/S0002-9610(99)00231-7
34. Hassoun HT, Kone BC, Mercer DW, Moody FG, Weisbrodt NW, Moore FA. Post-injury multiple organ failure: the role of the gut. Shock. 2001;15:1-10.
https://doi.org/10.1097/00024382-200115010-00001
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https://doi.org/10.1139/y82-201
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https://doi.org/10.1016/0016-5085(86)90078-8
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https://doi.org/10.1038/sj.mn.7800136
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https://doi.org/10.1097/00000542-200402000-00036
2. Chang PI, Rutlen DL. Effects of beta-adrenergic agonists on splanchnic vascular volume and cardiac output. Am J Physiol. 1991;261:H1499-507.
https://doi.org/10.1152/ajpheart.1991.261.5.H1499
3. Brooksby GA, Donald DE. Dynamic changes in splanchnic blood flow and blood volume in dogs during activation of sympathetic nerves. Circ Res. 1971;29:227-38.
https://doi.org/10.1161/01.RES.29.3.227
4. Scott-Douglas NW, Robinson VJ, Smiseth OA, Wright CI, Manyari DE, Smith ER, et al. Effects of acute volume loading and hemorrhage on intestinal vascular capacitance: a mechanism whereby capacitance modulates cardiac output. Can J Cardiol. 2002;18:515-22.
5. Rothe CF. Control of capacitance vessels. In: Shepherd AP, Granger DN, editors. Physiology of the intestinal circulation. New York: Raven; 1984. p. 73.
6. Rochat MC. An introduction to reperfusion injury. Compend Contin Educ Pract Vet. 1991;13:923-30.
7. Kong SE, Blennerhassett LR, Heel KA, McCauley RD, Hall JC. Ischaemia-reperfusion injury to the intestine. Aust NZ J Surg. 1998;68:554-61.
https://doi.org/10.1111/j.1445-2197.1998.tb02099.x
8. Moore FA, Sauaia A, Moore EE. Postinjury multiple organ failure: a bimodal phenomenon. J Trauma. 1996;40:501-12.
https://doi.org/10.1097/00005373-199604000-00001
9. Deitch EA. Multiple organ failure: Pathophysiology and poten- tial future therapy. Ann Surg. 1992;216:117-34.
https://doi.org/10.1097/00000658-199208000-00002
10. Deitch EA, Da-Zhong XU, Lu Q. Gut lymph hypothesis of early shock and trauma-induced multiple organ dysfunction syndrome: A new look at gut origin sepsis. J Organ Dysfunct. 2006;2:70-9.
https://doi.org/10.1080/17471060600551772
11. Ivatory RR, Simon RJ, Islam S, Fueg A, Rohman M, Stahl WM. A prospective, randomized study of end points of resuscitation after major trauma: Global oxygen transport indices versus organ-specific gastric mucosal pH. J Am Coll. 1996;183:145- 54.
12. Deitch EA. Intestinal permeability is increased in burn patients shortly after injury. Surgery. 1990;107:411-6.
13. Rush BF, Sori AJ, Murphy TF, Smith S, Flanagan JJ, Machiedo GW. Endotoxemia and bacteremia during hemorrhagic shock. Ann Surg. 1998;207:549-54.
https://doi.org/10.1097/00000658-198805000-00009
14. Doig CJ, Sutherland LR, Sandham JD, Fick GH, Verhoef M, Meddings JB. Increased intestinal permeability is associated with the development of multiple organ dysfunction syndrome in critically ill ICU patients. Am J Respir Crit Care Med. 1998;158:444-51.
https://doi.org/10.1164/ajrccm.158.2.9710092
15. Pober JS, Cotran RS. Cytokines and endothelial cell biology. Physiol Rev 1990;70:427-51.
https://doi.org/10.1152/physrev.1990.70.2.427
16. Goodman ER, Kleinstein E, Fusco AM, Quinlan DP, Lavery R, Livingston DH, et al. Role of interleukin 8 in the genesis of acute respiratory distress syndrome through an effect on neutrophil apoptosis. Arch Surg. 1998;133:1234-9.
https://doi.org/10.1001/archsurg.133.11.1234
17. Patrick DA, Moore FA, Moore EE, Barnett CC, Silliman CC. Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure. New Horiz. 1996;4:194- 210.
18. Langenfeld J, Livingston DH, Machiedo GW. Red blood cell deformability is an early indicator of infection. Surgery. 1991;110:398-403.
19. Livingston DH, Gentile P, Malangoni MA. Bone marrow failure after hemorrhagic shock. Circ Shock. 1990;30:255-63.
20. Balzan S, De Almeida C, De Cleva R, Zilberstein B, Cecconello I. Bacterial translocation: Overview of mechanisms and clinical impact. J Gastroenterol Hepatol. 2007;22:464-71.
https://doi.org/10.1111/j.1440-1746.2007.04933.x
21. Moore FA, Moore EE, Poggetti R, McAnena OJ, Peterson VM, Abernathy CM, et al. Gut bacterial translocation via the portal vein: A clinical perspective with major torso trauma. J Trauma. 1991;31:629-38.
https://doi.org/10.1097/00005373-199105000-00006
22. Lewis A, Harkin DW, D'Sa AA, McCallion K, Halliday MJ, Campbel, FC. Primed neutrophils in the venous effluent convert local to systemic inflammation after limb ischaemia-reperfusion injury. Br J Surg. 2001;88(Supp.1):3.
https://doi.org/10.1046/j.1365-2168.2001.01757-12.x
23. Ramaiah SK, Jaeschke H. Role of neutrophils in the patho- genesis of acute inflammatory liver injury. Toxicol Pathol. 2007;35:757-66.
https://doi.org/10.1080/01926230701584163
24. Moore FA, Moore EE, Poggetti R, McAnena OJ, Peterson VM, Abernathy CM, et al. Gut bacterial translocation via the portal vein: A clinical perspective with major torso trauma. J Trauma. 1991;31:629-38.
https://doi.org/10.1097/00005373-199105000-00006
25. Magnotti LJ, Upperman JS, Xu DZ, Lu Q, Deitch EA. Gut derived mesenteric lymph but not portal blood increases endo- thelial cell permeability and potentiates lung injury following hemorrhagic shock. Ann Surg. 1998;228:518-27.
https://doi.org/10.1097/00000658-199810000-00008
26. Davidson MT, Deitch EA, Lu Q, Osband A, Feketeova E, Nemeth ZH, et al. A study of the biologic activity of trauma- hemorrhagic shock mesenteric lymph over time and the relative role of cytokines. Surgery. 2004;136:32-41.
https://doi.org/10.1016/j.surg.2003.12.012
27. Nastos C, Kalimeris K, Papoutsidakis N, Defterevos G, Pafiti A, Kalogeropoulou H, et al. Antioxidant treatment attenuates intestinal mucosal damage and gut barrier dysfunction after major hepatectomy. Study in a porcine model. J Gastrointest Surg. 2011;15:809-17.
https://doi.org/10.1007/s11605-011-1475-0
28. Schoenberg MH, Beger HG. Reperfusion injury after intestinal ischemia. Crit Care Med. 1993;21:1376-87.
https://doi.org/10.1097/00003246-199309000-00023
29. Peters-Scholte C, Braun K, Koster J, Kops N. Effects of al- lopurinol and deferoxamine on reperfusion injury of the brain in newborn piglets after neonatal ihipoxia-ischemia. Pediatr Res. 2003;54:516-22.
https://doi.org/10.1203/01.PDR.0000081297.53793.C6
30. Yang H, Sheng Z, Guo Z, Shi Z, Lu J, Chai J, et al. Oxygen free radical injury and its relation to bacterial and endotoxin translocation after delayed fluid resuscitation: clinical and experimental study. Chin Med J (Engl). 1997;110:118-24.
31. Tandon P, García-Tsao G. Bacterial infections and multiorgan failure in cirrosis. Semin Liver Dis. 2008;28:26-42.
https://doi.org/10.1055/s-2008-1040319
32. Taylor DE. Reviving the motor of multiple organ dysfunction síndrome: Gut dysfunction in ARDS and multiorgan failure. Respir Care Clin North Am. 1998;4:611-31.
33. Moore FA. The role of the gastrointestinal tract in post-injury multiple organ failure. Am J Surg. 1999;178:449-53.
https://doi.org/10.1016/S0002-9610(99)00231-7
34. Hassoun HT, Kone BC, Mercer DW, Moody FG, Weisbrodt NW, Moore FA. Post-injury multiple organ failure: the role of the gut. Shock. 2001;15:1-10.
https://doi.org/10.1097/00024382-200115010-00001
35. Pastores SM, Katz DP, Kvetan V. Splachnic ischemia and gut mucosal injury in sepsis and the multiple organ dysfunction síndrome. Am J Gastroenterol. 1996;91:1697-710.
36. Nieuwenhuijzen GA, Goris RJ. The gut: The motor of multiple organ dysfunction syndrome? Curr Opin Nutr Metab Care. 1999;2:399-404.
https://doi.org/10.1097/00075197-199909000-00008
37. Taylor DE, Piantadosi CA. Oxidative metabolism in sepsis and sepsis síndrome. J Crit Care. 1995;10:122-35.
https://doi.org/10.1016/0883-9441(95)90003-9
38. Fares PL, Simon RJ, Martella AT. Intestinal permeability cor- relates with severity of injury in trauma patients. J Trauma. 1998;44:1031-6.
https://doi.org/10.1097/00005373-199806000-00016
39. Koike K, Moore EE, Moore FA. Gut ischemia/reperfusion produces lung injury independent of endotoxin. Crit Care Med. 1994;22:1438-44.
https://doi.org/10.1097/00003246-199409000-00014
40. Cem T, Ayhan K, Kessaf A. Prevention of deleterious effects of reperfusion injuryusing one week high dose allopurinol. Dig Dis Sci. 2001;40:430-7.
41. Dawiskiba T, Pupka A, Skora J, Janczak D, Pawtowski S, Krawczyk Z et al. The effect of allopurinol on intestinal ischemia-reperfusion injury development - the new approach. Chirurgia Polska. 2007;9:25-33.
42. Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesions in low-flow states. A morphological, hemody- namic and metabolic reappraisal. Arch Surg. 1970;101:478-83.
https://doi.org/10.1001/archsurg.1970.01340280030009
43. Peto K, Nemeth N, Brath E, Takacs IE, Baskurt OK, Meisel- man HJ, et al. The effects of renal ischemia-reperfusion on hemorheological factors: Preventive role of allopurinol. Clin Hemorheol Microcirc. 2007;37:347-58.
44. Ping-Guo Liu, Song-Qing He, Yan-Hong Z, Jian Wu. Pro- tective effects of apocynin and allopurinol on ischemia/ reperfusion-induced liver injury in mice. World J Gastroenterol. 2008;14:2832-7.
https://doi.org/10.3748/wjg.14.2832
45. Guide for the care and use of laboratory animals. NIH. Wash- ington, D.C.: National Academy Press; 1996. p. 11-40.
46. Mrad A. Ética en la investigación con modelos animales experimentales. Alternativas y las 3 R ́s de Russell. Una res- ponsabilidad y un compromiso ético que nos compete a todos. Rev Colomb Bioética. 2006;1:163-83.
47. Guyton AC, Jones CE, Coleman TG. Normal cardiac output and its variation. In: Guyton AC, Joes CE, Coleman TG, editors. Cardiac output and its regulation. Second edition. Philadelphia: WB Saunders Company; 1973. p. 3-29.
48. Parks DA, Granger DN. Contributions of ischemia and reperfu- sion to mucosal lesion. Am J Physiol. 1986;250:G749-53.
https://doi.org/10.1152/ajpgi.1986.250.6.G749
49. McCord JM, Fridovich I. The reduction of cytochrome c by milk xanthine oxidase. J Biol Chem. 1968;243:5753-60.
50. McCord JM, Roy RS. The pathophysiology of superoxide: Roles in inflammation and ischemia. Can J Physiol Pharmacol. 1982;60:1346-52.
https://doi.org/10.1139/y82-201
51. Parks DA, Bulkley GB, Granger DN, Hamilton SR, McCord JM. Ischemic injury in the cat small intestine: Role of super- oxide radicals. Gastroenterology. 1982;82:9-15.
https://doi.org/10.1016/0016-5085(82)90115-9
52. Granger DN, McCord JM, Parks DA, Hollwarth ME. Xan- thine oxidase inhibitors attenuate ischemia-induced vascular permeability changes in the cat intestine. Gastroenterology. 1986;90:80-4.
https://doi.org/10.1016/0016-5085(86)90078-8
53. Meneshian A, Bulkley GB. The physiology of endothelial xan- thine oxidase: From urate catabolism to reperfusion injury to inflammatory signal ransduction. Microcirculation. 2002;9:161- 75.
https://doi.org/10.1038/sj.mn.7800136
54. Parks DA, Williams TK, Beckman JS. Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevalu- ation. Am J Physiol. 1988;254:768-74.
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2012-07-01
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Riveros, E.; Pérez, I.; Becerra, K.; Bustamante, M.; Millán, C.; Manrique, F. El Pretratamiento Con Alopurinol Disminuye La translocación Bacteriana Y atenúa Los Cambios morfológicos De La Mucosa Intestinal En Un Modelo De Isquemia-reperfusión Intestinal En Ratas. Rev Colomb Cir 2012, 27, 227-234.
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