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. 2004 Jul;65(4):373–382. doi: 10.1016/j.curtheres.2004.07.001

Effects of cimetidine, a histamine type 2 receptor antagonist, on microcirculatory disturbance of the stomach induced by full-thickness burn injuries as a model for surgical stress in rats

Hideki Ishikawa 1,*, Masashi Yoshida 2, Go Wakabayashi 2, Yoshihide Otani 2, Motohide Shimazu 2, Tetsuro Kubota 2, Koichiro Kumai 2, Naoki Aikawa 1, Masaki Kitajima 2
PMCID: PMC3964572  PMID: 24672092

Abstract

Background

We have reported the preventive effect of cimetidine, a histamine type 2 receptor antagonist, on decreased gastric mucosal blood flow induced by burn injury, a model of surgical stress.

Objective

The present study was performed to assess the effects of cimetidine on gastric microcirculatory disturbance induced by surgical stress.

Methods

Twelve male Wistar rats were anesthetized and a 30% full-thickness dorsal scald burn was inflicted. The total lengths of gastric erosions were measured using stereoscopic microscopy. Microvascular images in the basal region of the gastric mucosa were observed using an intravital microscope, and the diameters of venules and collecting venules were measured. Rolling leukocytes inside and along the venules, an indication of endothelial damage to the microcirculation, were observed. The rats were assigned to the cimetidine group or the control group (both, n = 6). Cimetidine 100 mg/kg was administered 30 minutes before and 2.5 hours after infliction of the burn injury. Animals in the control group were given only isotonic saline. Values are expressed as mean (SD).

Results

Contraction of venules was easily observed in all rats in the control group. However, venular contraction was rarely observed in the cimetidine group. The total length of gastric erosions was significantly decreased in the cimetidine group compared with the control group (0.93 [0.58] μm vs 5.98 [5.18] μm, respectively; P < 0.05). The percentages of rolling leukocytes that passed the confluence of a prevenule and a venule were also significantly decreased in the cimetidine group compared with the control group (4.7% [7.3%] vs 22.6% [5.7%]; P < 0.01). The diameters of the venules and collecting venules were significantly larger in the cimetidine group (57.3 [6.8] μm and 75.9 [3.6] μm, respectively) than in the control group (30.9 [9.2] μm and 46.8 [8.0] μm, respectively) (both, P < 0.01).

Conclusions

The present study suggests that cimetidine may have a protective effect against gastric microcirculatory disturbances induced by burn injury, a model of surgical stress.

Keywords: histamine type 2 receptor antagonist, cimetidine, thermal injury, gastric microcirculation, gastric mucosal lesion, endothelial damage

Full Text

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Footnotes

This article was presented in part in the free paper session at International Surgical Week '97, Acapulco, Mexico, August 24–30, 1997 (Session 133.07, Abstract 711).

References

  • 1.Davenport HW. Salicylate damage to the gastric mucosal barrier. N Engl J Med. 1967;276:1307–1312. doi: 10.1056/NEJM196706082762308. [DOI] [PubMed] [Google Scholar]
  • 2.Kamada T, Sato N, Kawano S. Gastric mucosal hemodynamics after thermal or head injury. A clinical application of reflectance spectrophotometryGastroenterology. 1982;83:535–540. [PubMed] [Google Scholar]
  • 3.Kitajima M, Wolfe RR, Trelstad RL. Gastric mucosal lesions after burn injury: Relationship to H+ back-diffusion and the microcirculation. J Trauma. 1978;18:644–650. [PubMed] [Google Scholar]
  • 4.Yoshida M, Fukumura D, Wakabayashi G. Gastric microcirculatory disturbance and behavior of leukocytes after thermal injury: Intravital observation of arteriovenous shunting channels in the gastric submucosal layer. J Gastroenterol Hepatol. 1995;10:365–370. doi: 10.1111/j.1440-1746.1995.tb01585.x. [DOI] [PubMed] [Google Scholar]
  • 5.Arakawa T, Nakamura H, Chono S. Difference in mode of action of cimetidine and gefarnate on endogenous prostacyclin, prostaglandin E2 and thromboxane in rat gastric mucosa. Tohoku J Exp Med. 1983;40:407–412. doi: 10.1620/tjem.140.407. [DOI] [PubMed] [Google Scholar]
  • 6.Tayama E, Hayashida N, Fukunaga S. High-dose cimetidine reduces proinflammatory reaction after cardiac surgery with cardiopulmonary bypass. Ann Thorac Surg. 2001;72:1945–1949. doi: 10.1016/s0003-4975(01)03225-8. [DOI] [PubMed] [Google Scholar]
  • 7.Hiramoto JS, Terdiman JP, Norton JA. Evidence-based analysis: Postoperative gastric bleeding: Etiology and prevention. Surg Oncol. 2003;12:919. doi: 10.1016/s0960-7404(02)00073-7. [DOI] [PubMed] [Google Scholar]
  • 8.McElwee HP, Sirinek KR, Levine RA. Cimetidine affords protection equal to antacids in prevention of stress ulceration following thermal injury. Surgery. 1979;86:620–626. [PubMed] [Google Scholar]
  • 9.Kitajima M, Ikeda Y, Ueda M, Sohma S. The microcirculation of the stomach in stress. In: Tsuchiya M, Asano M, Oda M, editors. Basic Aspects of Microcirculation: Proceedings of the Tokyo International Symposium on Microcirculation; July 26, 1981; Bethesda, Md: Excerpta Medica; 1982. pp. 230–242. [Google Scholar]
  • 10.Wakabayashi G, Ueda M, Aikawa N, Abe O. Atrial natriuretic polypeptide after burn injury: Blood levels and physiological role in rats. Burns. 1990;16:169–175. doi: 10.1016/0305-4179(90)90032-r. [DOI] [PubMed] [Google Scholar]
  • 11.Carter EA, Gonnella A, Tompkins RG. Increased transcellular permeability of rat small intestine after thermal injury. Burns. 1992;18:117–120. doi: 10.1016/0305-4179(92)90007-h. [DOI] [PubMed] [Google Scholar]
  • 12.Yoshida M, Wakabayashi G, Otani Y. Intravital observation of gastric micro-circulatory disturbance induced by thermal injury. In: Tsuchiya M, Asano M, Tsushima N, editors. Microcirculation Annual 1996. Nihon-Igakukan; Princeton, NJ: 1996. pp. 203–204. [Google Scholar]
  • 13.Ohno T, Katori M, Nishiyama K, Saigenji K. Direct observation of microcirculation of the basal region of rat gastric mucosa. J Gastroenterol. 1995;30:557–564. doi: 10.1007/BF02367779. [DOI] [PubMed] [Google Scholar]
  • 14.Rosenberg A, Guth PH. A method for the in vivo study of the gastric microcirculation. Microvasc Res. 1970;2:111–112. doi: 10.1016/0026-2862(70)90056-7. [DOI] [PubMed] [Google Scholar]
  • 15.Guth PH, Rosenberg A. In vivo microscopy of the gastric microcirculation. Am J Dig Dis. 1972;17:391–398. doi: 10.1007/BF02231290. [DOI] [PubMed] [Google Scholar]
  • 16.Suematsu M, Delano FA, Poole D. Spatial and temporal correlation between leukocyte behavior and cell injury in postischemic rat skeletal muscle microcirculation. Lab Invest. 1994;70:684–695. [PubMed] [Google Scholar]
  • 17.Yoshida M, Kitahora T, Wakabayashi G. Active oxygen species in formation of acute gastric mucosal lesions induced by thermal injury in rats. Dig Dis Sci. 1995;40:1306–1310. doi: 10.1007/BF02065543. [DOI] [PubMed] [Google Scholar]
  • 18.Kitahora T, Suzuki K, Asakura H. Active oxygen species generated by monocytes and polymorphonuclear cells in Crohn's disease. Dig Dis Sci. 1988;33:951–955. doi: 10.1007/BF01535990. [DOI] [PubMed] [Google Scholar]
  • 19.Kitajima M, Otsuka S, Shimizu A. Impairment of gastric microcirculation in stress. J Clin Gastroenterol. 1988;10(Suppl 1):S120–S128. doi: 10.1097/00004836-198812001-00018. [DOI] [PubMed] [Google Scholar]
  • 20.Yoshida M, Wakabayashi G, Otani Y. Active oxygen species generation by circulating leukocytes and gastric submucosal microcirculatory disturbances in the early period after thermal injury. J Clin Gastroenterol. 1995;21(Suppl 1):S87–S92. [PubMed] [Google Scholar]
  • 21.Yoshida N, Yoshikawa T, Nakamura Y. Role of neutrophil-endothelial cell interactions in gastric mucosal injury induced by aspirin. J Clin Gastroenterol. 1995;21(Suppl 1):S73–S77. [PubMed] [Google Scholar]
  • 22.Yoshida N, Yoshikawa T, Nakamura Y. Role of neutrophil-mediated inflammation in aspirin-induced gastric mucosal injury. Dig Dis Sci. 1995;40:2300–2304. doi: 10.1007/BF02063228. [DOI] [PubMed] [Google Scholar]
  • 23.Yoshida M, Wakabayashi G, Ishikawa H. A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats. J Gastroenterol Hepatol. 1998;13:104–108. doi: 10.1111/j.1440-1746.1998.tb00553.x. [DOI] [PubMed] [Google Scholar]
  • 24.Ishikawa H, Yoshida M, Wakabayashi G. Sialyl Lewis X analog attenuates gastric microcirculatory disturbance and gastric mucosal erosion induced by thermal injury in rats. J Gastroenterol Hepatol. 2003;18:47–52. doi: 10.1046/j.1440-1746.2003.02908.x. [DOI] [PubMed] [Google Scholar]
  • 25.Nakamura M, Oda M, Kaneko K. Radioautographic characterization of H1 and H2 receptor antagonists—binding sites in rat gastric mucosal micro-circulatory system. In: Shu C, editor. Vascular Endothelium in Health and Disease. Plenum Press; Tokyo: 1988. pp. 151–160. [PubMed] [Google Scholar]
  • 26.Lapenna D, De Gioia S, Mezzetti A. H2-receptor antagonists are scavengers of oxygen radicals. Eur J Clin Invest. 1994;24:476–481. doi: 10.1111/j.1365-2362.1994.tb02378.x. [DOI] [PubMed] [Google Scholar]
  • 27.Okajima K, Koga S, Inoue M. Inhibitory effect of cimetidine on reactive oxygen production by leukocytes and leukocyte aggregation. Igaku-no Ayumi. 1989;149:69–70. [in Japanese] [Google Scholar]
  • 28.Kirkova M, Atanassova M, Russanov E. Effects of cimetidine and its metal complexes on nitroblue tetrazolium and ferricytochrome c reduction by superoxide radicals. Gen Pharmacol. 1999;33:271–276. doi: 10.1016/s0306-3623(99)00015-4. [DOI] [PubMed] [Google Scholar]
  • 29.Lambat Z, Limson JL, Daya S. Cimetidine: Antioxidant and metal-binding properties. J Pharm Pharmacol. 2002;54:1681–1686. doi: 10.1111/j.2042-7158.2002.tb02404.x. [DOI] [PubMed] [Google Scholar]

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