PURPOSE:
Previously we demonstrated that peritoneal lavage with high concentrations of adenosine (1 mM) provides pharmacologic levels of adenosine in the intestines without elevating adenosine levels in the systemic circulation and without causing systemic hemodynamic effects (Alimentary Pharmacology & Therapeutics 2000;14:1371–80). Because adenosine can be safely administered into the peritoneal cavity, and because it inhibits fibroblast proliferation and collagen production and inflammation and enhances angiogenesis, we tested the hypothesis that adenosine applied into the abdominal cavity safely and effectively reduces formation of abdominal adhesions.
METHODS:
To test this hypothesis, in Sprague-Dawley rats, a window of right parietal peritoneum was removed and the cecum was brushed and placed next to the damaged peritoneum. After injury, rats received in the abdominal cavity either 20 ml of saline (n = 12, Saline Group) or 20 ml of 1 mM adenosine (n = 12, Adenosine 1X Group; and n = 12, Adenosine 4X Group). At 24, 48, and 72 hours after surgery, rats received by intraperitoneal injection either 10 ml of saline (Saline Group and Adenosine 1X Group) or 10 ml of 1 mM adenosine (Adenosine 4X Group).
RESULTS:
After 14 days, the degree of adhesion formation was scored (0 to 4) by a blinded observer. Animals tolerated the adenosine treatments without signs of discomfort or distress. The adhesion scores were 2.6 ± 0.34, 1.7 ± 0.40, and 0.74 ± 0.29 in the Saline, Adenosine 1X, and Adenosine 4X groups, respectively (P = 0.0035, Kruskal-Wallis analysis of variance).
CONCLUSION:
Peritoneal administration of 1 mM adenosine safely and effectively reduces adhesion formation.
Similar content being viewed by others
REFERENCES
H Ellis (1982) ArticleTitleThe causes and prevention of intestinal adhesions Br J Surg 69 241–3 Occurrence Handle1:STN:280:Bi2C1czkt1Y%3D Occurrence Handle7042032
D Menzies (1993) ArticleTitlePostoperative adhesions: their treatment and relevance in clinical practice Ann R Coll Surg Engl 75 147–53 Occurrence Handle1:STN:280:ByyA3M7ptFA%3D
D Menzies (1992) ArticleTitlePeritoneal adhesions: incidence, cause, and prevention Surg Ann 24 27–45
GS diZerega (1992) The peritoneum: postsurgical repair and adhesion formation JA Rock AA Murphy HW Jones (Eds) Female reproductive surgery Williams & Wilkins Boston 2–18
SM Kavic SM Kavic (2002) ArticleTitleAdhesions and adhesiolysis: the role of laparoscopy J Soc Laparoendosc Surg 6 99–109
DM Scott-Coombes MN Vipond JM Thompson (1993) ArticleTitleGeneral surgeons’ attitudes to the treatment and prevention of abdominal adhesions Ann R Coll Surg Engl 75 123–8 Occurrence Handle1:STN:280:ByyB3snisFM%3D Occurrence Handle8476180
MP Diamond ML Freeman (2001) ArticleTitleClinical implications of postsurgical adhesions Hum Reprod Update 7 567–76 Occurrence Handle1:STN:280:DC%2BD3MnotFKitQ%3D%3D Occurrence Handle11727865
RK Dubey DG Gillespie Z Mi EK Jackson (2001) ArticleTitleEndogenous cyclic AMP-adenosine pathway regulates cardiac fibroblast growth Hypertension 37 1095–100 Occurrence Handle1:CAS:528:DC%2BD3MXjtFChsb0%3D Occurrence Handle11304509
RK Dubey DG Gillespie LC Zacharia Z Mi EK Jackson (2001) ArticleTitleA2B receptors mediate the antimitogenic effects of adenosine in cardiac fibroblasts Hypertension 37 716–21 Occurrence Handle1:CAS:528:DC%2BD3MXhvVSrsr4%3D Occurrence Handle11230362
RK Dubey DG Gillespie Z Mi EK Jackson (2000) ArticleTitleCardiac fibroblasts express the cAMP-adenosine pathway Hypertension 36 337–42 Occurrence Handle1:CAS:528:DC%2BD3cXntV2gtr4%3D Occurrence Handle10988261
RK Dubey DG Gillespie EK Jackson (1998) ArticleTitleAdenosine inhibits collagen and protein synthesis in cardiac fibroblasts: role of A2B receptors Hypertension 31 943–48 Occurrence Handle1:CAS:528:DyaK1cXisFajsrw%3D Occurrence Handle9535419
RK Dubey DG Gillespie Z Mi EK Jackson (1997) ArticleTitleExogenous and endogenous adenosine inhibits fetal calf serum-induced growth of rat cardiac fibroblasts: role of A2B receptors Circulation 96 2656–66 Occurrence Handle1:CAS:528:DyaK2sXnt1Kkt7s%3D Occurrence Handle9355907
EK Jackson RS Swamy WA Herzer Z Mi (2000) ArticleTitleLocal and systemic effects of peritoneal lavage with high concentrations of adenosine in rats Aliment Pharmacol Ther 14 1371–80 Occurrence Handle1:CAS:528:DC%2BD3cXotV2jtrg%3D Occurrence Handle11012485
L Holmdahl (1997) ArticleTitleThe role of fibrinolysis in adhesion formation Eur J Surg 163 24–31
GS diZerega (1997) ArticleTitleBiochemical events in peritoneal tissue repair Eur J Surg 163 10–6
H Ellis (1997) ArticleTitleThe clinical significance of adhesions: focus on intestinal obstruction Eur J Surg 163 5–9
H Ellis (1962) ArticleTitleThe aetiology of post-operative abdominal adhesions: an experimental study Br J Surg 50 10–6 Occurrence Handle1:STN:280:CC2D3s7jtVI%3D Occurrence Handle13889984
N Chegini (1997) ArticleTitleThe role of growth factors in peritoneal healing: transforming growth factor β (TGF-β) Eur J Surg 163 17–23
H Rong X-M Tang Y Zhao et al. (1997) ArticleTitlePostsurgical intraperitoneal exposure to glove powders modulates inflammatory and immune-related cytokine production Wound Repair Regen 5 89–96
DW Milligan AT Raftery (1974) ArticleTitleObservations on the pathogenesis of peritoneal adhesions: a light and electron microscopical study Br J Surg 61 274–80 Occurrence Handle1:STN:280:CSuC2sjjt1Y%3D Occurrence Handle4832632
ES Klein SS Asculai GY Ben-Ari (1996) ArticleTitleEffects of hyaluronic acid on fibroblast behavior in peritoneal injury J Surg Res 61 473–6 Occurrence Handle1:CAS:528:DyaK28Xitlansrg%3D Occurrence Handle8656628
M Klinger M Freissmuth C Nanoff (2002) ArticleTitleAdenosine receptors: G protein-mediated signalling and the role of accessory proteins Cell Signal 14 99–108 Occurrence Handle1:CAS:528:DC%2BD38XitlWktA%3D%3D Occurrence Handle11781133
E Ongini BB Fredholm (1996) ArticleTitlePharmacology of adenosine A2A receptors Trends Pharmacol Sci 17 364–72 Occurrence Handle1:CAS:528:DyaK28Xnt1Kiu7Y%3D Occurrence Handle8979771
Feoktistov I, Goldstein AE, Ryzhov S, et al. (2002) “Differential expression of adenosine receptors in human endothelial cells: role of A2B receptors in angiogenic factor regulation.” Circ Res 90:531–8.
RK Dubey DG Gillespie EK Jackson (2002) ArticleTitleA2B adenosine receptors stimulate growth of porcine and rat arterial endothelial cells Hypertension 39 530–5 Occurrence Handle1:CAS:528:DC%2BD38Xhs1Wlurw%3D Occurrence Handle11882603
MB Grant MI Davis S Caballero I Feoktistov I Biaggioni L Belardinelli (2001) ArticleTitleProliferation, migration, and ERK activation in human retinal endothelial cells through A2B adenosine receptor stimulation Invest Ophthalmol Vis Sci 42 2068–73 Occurrence Handle1:STN:280:DC%2BD3MvjtlKgtw%3D%3D Occurrence Handle11481274
MC Montesinos P Gadangi M Longaker et al. (1997) ArticleTitleWound healing is accelerated by agonists of adenosine A2 (G αs-linked) receptors J Exp Med 186 1615–20 Occurrence Handle1:CAS:528:DyaK2sXntFerurg%3D Occurrence Handle9348321
IS Yuh BB Jang BJ Hong (1998) ArticleTitleEffects of adenosine and epidermal growth factor on the growth of mouse mammary epithelial cells Cell Biol Int 22 131–5 Occurrence Handle1:CAS:528:DyaK1MXlvVSmtQ%3D%3D Occurrence Handle9878100
PM Kaminski KG Proctor (1989) ArticleTitleAttenuation of no-reflow phenomenon, neutrophil activation, and reperfusion injury in intestinal microcirculation by topical adenosine Circ Res 65 426–35 Occurrence Handle1:CAS:528:DyaL1MXltVykurk%3D Occurrence Handle2665971
JE Jordan ZQ Zhao H Sato S Taft J Viten-Johansen (1997) ArticleTitleAdenosine A2 receptor activation attenuates reperfusion injury by inhibiting neutrophil accumulation, superoxide generation and coronary endothelial adherence J Pharmacol Exp Ther 280 301–9 Occurrence Handle1:CAS:528:DyaK2sXntFersA%3D%3D Occurrence Handle8996210
MD Okusa J Linden L Huang JM Rieger TL Macdonald LP Huynh (2000) ArticleTitleA2A adenosine receptor-mediated inhibition of renal injury and neutrophil adhesion. Am J Physiol Renal Physiol 279 F809–18 Occurrence Handle1:CAS:528:DC%2BD3cXotFartro%3D Occurrence Handle11053040
G Sandberg (1983) ArticleTitleRegulation of thymocyte proliferation by endogenous adenosine and adenosine deaminase Int J Immunopharmacol 5 259–65 Occurrence Handle1:CAS:528:DyaL3sXmtFWjsrw%3D Occurrence Handle6605314
Y Nishida N Kamatani T Morito T Miyamoto (1984) ArticleTitleDifferential inhibition of lymphocyte function by 2-chloroadenosine Int J Immunopharmacol 6 335–8 Occurrence Handle1:STN:280:BiqD3crovVE%3D Occurrence Handle6480196
A Colquhoun EA Newsholme (1997) ArticleTitleInhibition of human tumor cell proliferation by analogues of adenosine Cell Biochem Funct 15 135–9 Occurrence Handle1:CAS:528:DyaK2sXltVyisLo%3D Occurrence Handle9253166
DR Wagner C McTiernan VJ Sanders AM Feldman (1998) ArticleTitleAdenosine inhibits lipopolysaccharide-induced secretion of tumor necrosis factor–alpha in the failing human heart Circulation 97 521–4 Occurrence Handle1:CAS:528:DyaK1cXhsVGrsLw%3D Occurrence Handle9494021
BS Cain DR Meldrum CA Dinarello X Meng A Banerjee AH Harken (1998) ArticleTitleAdenosine reduces cardiac TNF-α production and human myocardial injury following ischemia-reperfusion J Surg Res 76 117–23 Occurrence Handle1:CAS:528:DyaK1cXlsFWqs70%3D Occurrence Handle9698510
Z Zidek (1999) ArticleTitleAdenosine - cyclic AMP pathways and cytokine expression Eur Cytokine Netw 10 319–28 Occurrence Handle1:CAS:528:DyaK1MXms1ajtrc%3D Occurrence Handle10477388
JC Shryock L Belardinelli (1997) ArticleTitleAdenosine and adenosine receptors in the cardiovascular system: biochemistry, physiology, and pharmacology Am J Cardiol 79 2–10 Occurrence Handle1:CAS:528:DyaK2sXltFChtro%3D
H Van Belle (1969) ArticleTitleUptake and deamination of adenosine by blood: species differences, effect of pH, ions, temperature and metabolic inhibitors Biochim Biophys Acta 192 124–32 Occurrence Handle1:CAS:528:DyaF1MXltFSls70%3D Occurrence Handle5347963
SM Jarvis JR Hammond AR Paterson AS Clanachan (1982) ArticleTitleSpecies differences in nucleoside transport: a study of uridine transport and nitrobenzylthioinosine binding by mammalian erythrocytes Biochem J 208 83–8 Occurrence Handle1:CAS:528:DyaL3sXht1egt70%3D Occurrence Handle7159400
Zimmerman, H (2001) “Ecto-nucleotidases” In: Handbook of experimental pharmacology. Purinergic and pryimidinergic signalling. I. Molecular, nervous and urogenitary system function, Abbracchio MP, Williams M (eds.), Springer-Verlag, New York, pp 209–50
ACKNOWLEDGMENT
The author thanks Zaichuan Mi, who performed the blinded adhesion scoring.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by The Center for Clinical Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania.
About this article
Cite this article
Jackson, E. Intraperitoneal Administration of Adenosine Inhibits Formation of Abdominal Adhesions. Dis Colon Rectum 47, 1390–1396 (2004). https://doi.org/10.1007/s10350-004-0578-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10350-004-0578-z