Abstract
The purpose of this study was to evaluate the effects of systemic and intra-arterial application of heparin by measuring tissue levels of inflammatory cytokines. Twenty-one adult male Wistar albino rats were divided into three groups (Group A, B and C). All the rats had undergone ligation of the right femoral artery with 4-0 silk suture to induce limb ischemia. Group A was the control group. In Group B, unfractionated heparin of 1500 U/kg/day was given through the tail vein for 10 days, the same dose was given to distal part of ligated right femoral artery for 10 days in Group C. On the 3rd, 5th, and 10th days, biopsies were taken from rectus femoris muscle on the ischemic extremities. Tumor necrosis factor-α, interleukin-1β, and vascular cell adhesion molecule levels in muscle tissue were measured by a standard enzyme-linked immunoabsorbent assay method. An increase in tumor necrosis factor-α level was found in all three groups throughout the duration of the experiment. The increase in Group C was statistically significant as compared with the other groups. The significant increases that occurred in tumor necrosis factor-α level as a result of intra-arterial application of heparin can be postulated to be one of the results of angiogenesis induced by the heparin in ischemic extremities. This might delay the formation of a necrosis in ischemic extremities, depending on the increased angiogenesis response by means of intra-arterial heparin application and may result in extended vitality of an extremity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Karapolat S, Dag O, Abanoz M, Aslan M. Arterial embolectomy, a retrospective evaluation of 730 cases over 20 years. Surg Today. 2006,36, 416–419
Sugano M, Tsuchida K, Hata T, Makino N. In vivo transfer of soluble TNF-α receptor 1 gene improves cardiac function and reduces infarct size after myocardial infarction in rats. Faseb J. 2004,18, 911–913
Shteinberg D, Halak M, Shapiro S, Kinarty A, Sobol E, Lahat N, et al. Abdominal aortic aneurysm and aortic occlusive disease, a comparison of risk factors and inflammatory response. Eur J Vasc Endovasc Surg. 2000,20, 462–465
Mousa SA. Heparin, low molecular weight heparin, and derivatives in thrombosis, angiogenesis, and inflammation, emerging links. Semin Thromb Hemost. 2007,33, 524–533
Khorana AA, Sahni A, Altland OD, Francis CW. Heparin inhibition of endothelial cell proliferation and organization is dependent on molecular weight. Arterioscler Thromb Vasc Biol. 2003;23: 2110–2115
Singh S, Padmanabhan R, Singh G, Kaur G. Effect of maternal hypervitaminosis A during late gestation on pre- & postnatal lung maturation in rat. Indian J Exp Biol. 1983, 3, 103–107
Schreyer SA, Peschon JJ, LeBoeuf RC. Accelerated atherosclerosis in mice lacking tumor necrosis factor receptor p55. J Biol Chem. 1996,271, 26174–26178
Sugano M, Tsuchida K, Makino N. Intramuscular gene transfer of soluble tumor necrosis factor-alpha receptor 1 activates vascular endothelial growth factor receptor and accelerates angiogenesis in a rat model of hindlimb ischemia. Circulation 2004,109, 797–802
Collen A, Smorenburg SM, Peters E, Lupu F, Koolwijk P, Van Noorden C, et al. Unfractionated and low molecular weight heparin affect fibrin structure and angiogenesis in vitro. Cancer Res. 2000,60, 6196–6200
Guo DQ, Wu LW, Dunbar JD, Ozes ON, Mayo LD, Kessler KM, et al. Tumor necrosis factor employs a protein-tyrosine phosphatase to inhibit activation of KDR and vascular endothelial cell growth factorinduced endothelial cell proliferation. J Biol Chem. 2000,275, 11216–11221
Roesel JF, Nanney LB. Assessment of differential cytokine effects on angiogenesis using an in vivo model of cutaneous wound repair. J Surg Res. 1995,58, 449–459
Cervera A, Justicia C, Reverter JC, Planas AM, Chamorro A. Steady plasma concentration of unfractionated heparin reduces infarct volume and prevents inflammatory damage after transient focal cerebral ischemia in the rat. J Neurosci Res. 2004,77, 565–572
Carroll SM, White FC, Roth DM, Bloor CM. Heparin accelerates coronary collateral development in a porcine model of coronary artery occlusion. Circulation 1993,88, 198–207
Chamorro A, Cervera A, Castillo J, Davalos A, Aponte JJ, Planas AM. Unfractionated heparin is associated with a lower rise of serum vascular cell adhesion molecule-1 in acute ischemic stroke patients. Neurosci Lett. 2002,328, 229–232
O’Blenes SB, Merklinger SL, Jegatheeswaran A, Campbell A, Rabinovitch M, Rebeyka I, et al. Low molecular weight heparin and unfractionated heparin are both effective at accelerating pulmonary vascular maturation in neonatal rabbits. Circulation 2003,108, 161–166
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Karapolat, S., Erkut, B. Effects of intra-arterial heparin on cytokine levels in the ischemic tissue. cent.eur.j.med 5, 165–171 (2010). https://doi.org/10.2478/s11536-009-0091-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.2478/s11536-009-0091-9