Effect of Pentoxifylline on Platelet - Activating Factor Production in Acute Limb Ischemic - Reperfusion Injury
Abstract
Background. In Acute limb ischemia reperfusion causes further damage to the ischemic tissue through local compartment syndrome, and systemic syndrome: multiorgan dysfunction and failure. Several method and attempt had been studied and performed to prevent and attenuate reperfusion injury such as, ischemic preconditioning, antioxidant, and anti-cytokine therapy, but their clinical benefit were not satisfactory. Pentoxifylline (PTX) a nonspesifik phosphodiesterase derivate of xanthine has emerged as a promising agent that may attenuate inflammation response through several mechanism. However, studies on PTX and its function to prevent and attenuate inflammation response through attenuating Platelet-Activating Factor (PAF) in acute limb ischemic were not consistent. The aim of this study is to investigate the effect of PTX on PAF in rabbits with acute limb ischemic-reperfusion injury.Methods and results.Acute limb Ischemia were performed by direct occlusion of the left femoral artery of 10 New Zealand White male rabbit using non traumatic clamp, and followed by releasing the clamp after 3 hours of occlusion. The rabbits were randomly separated into 2 groups of five (PTX group and control group). The PTX group was given PTX 40 mg/kg bolus half an hour prior to reperfusion, followed by maintenance dose 1 mg/kg/hour until 2 hour post reperfusion, while the control group was given normal saline solution with comparable volume and rate administration. Level of PAF were measured after 2.5 hour of ischemic period and after 2 hours of reperfusion period. After 2.5 hours of ischemic period, the mean PAF levels did not show any significant difference (p=0.754), the mean PAF level of PTX group 13.09±0.41 pg/mL, while the control group 13.38±0.28 pg/mL. After 2 hours period of reperfusion, there were significant differences of mean PAF level between the two groups (p=0.009). The mean PAF level in the control group increase by 12.11±0.79 to became 25.5±0.78 pg/dL, while the mean PAF level of the PTX group decrease by 1.73±1.1 pg/mL and became 11.36±0.78 pg/mL.
Conclusions. Pentoxifylline attenuate the production Platelet-Activating Factor level in rabbits with acute limb ischemic-reperfusion injury.
Downloads
Download data is not yet available.
References
Khanna A, Cowled PA, Fitridge RA. Nitric oxide and skeletal muscle reperfusion injury: current contro-versies (research review). J Surg.Res. 2005;128:98-107.
Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc.Surg. 2002;10:620-30.
Defraigne JO, Pincemail J. Local and systemic consequences of severe ischemia and reperfusion of the skeletal muscle. Physiopathology and prevention. Acta Chir Belg. 1998;98:176-86.
Matuschak GM. Multi Organ system Failure : Clinal Expression, Phatogenesis, and Therapy, In: Tak PP, Firestein GM, editors. General Management of Patient. New York: Springer-Verlag;2001. p. 221-47.
Coe DA, Freischlag JA, Johnson D, Mudaliar JH, Kosciesza SA, Traul DKet al.Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury. J.Surg.Res. 1997;67:21-25.
Odeh M. The role of reperfusion-induced injury in the pathogenesis of the crush syndrome. N.Engl.J Med 1991;324:1417-22.
Kishi M, Tanaka H, Seiyama A, Takaoka M, Matsuoka T, Yoshioka Tet al.Pentoxifylline attenuates reperfusion injury in skeletal muscle after partial ischemia. Am.J.Physiol 1998;274:H1435-H1442.
Zimmerman GA, McIntyre TM, Prescott SM, Stafforini DM. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med 2002;30:S294-S301.
Montrucchio G, Alloatti G, Camussi G. Role of platelet-activating factor in cardiovascular pathophysiology. Physiol Rev. 2000;80:1669-99.
Adams JG, Jr., Dhar A, Shukla SD, Silver D. Effect of pentoxifylline on tissue injury and platelet-activating factor production during ischemia-reperfusion injury. J.Vasc.Surg. 1995;21:742-48.
Silver D, Dhar A, Slocum M, Adams JG, Jr., Shukla S. Role of platelet-activating factor in skeletal muscle ischemia-reperfusion injury. Adv.Exp.Med.Biol. 1996; 416:217-21.
Iwai A, Itoh M, Yokoyama Y, Yasue N, Miyamoto T, Joh Tet al.Role of PAF in ischemia-reperfusion injury in the rat stomach. Scand.J.Gastroenterol.Suppl 1989;162: 63-66
Black SC, Driscoll EM, Lucchesi BR. Inhibition of platelet-activating factor fails to limit ischemia and reperfusion-induced myocardial damage. J.Cardiovasc.Pharmacol. 1992;20:997-1005.
Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Br.Med.Bull. 2004;70:71-86.
Clark SC, Rao JN, Flecknell PA, Dark JH. Pentoxifylline is as effective as leukocyte depletion for modulating pulmonary reperfusion injury. J.Thorac.Cardiovasc.Surg. 2003;126:2052-57.
Freitas JP, Filipe PM. Pentoxifylline. A hydroxyl radical scavenger. Biol.Trace Elem.Res. 1995;47:307-11.
Coe DA, Freischlag JA, Johnson D, Mudaliar JH, Kosciesza SA, Traul DKet al.Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury. J Surg.Res. 1997;67:21-25.
Doherty GM, Jensen JC, Alexander HR, Buresh CM, Norton JA. Pentoxifylline suppression of tumor necrosis factor gene transcription. Surgery 1991;110:192-98.
Sullivan GW, Carper HT, Novick WJ, Jr., Mandell GL. Inhibition of the inflammatory action of interleukin-1 and tumor necrosis factor (alpha) on neutrophil function by pentoxifylline. Infect.Immun. 1988;56:1722-29.
Muller JM, Vollmar B, Menger MD. Pentoxifylline reduces venular leukocyte adherence (“reflow paradox”) but not microvascular “no reflow” in hepatic ischemia/reperfusion. J.Surg.Res. 1997;71:1-6.
Chapelier A, Reignier J, Mazmanian M, Detruit H, Dartevelle P, Parquin Fet al.Pentoxifylline and lung ischemia-reperfusion injury: application to lung trans-plantation. Universite Paris-Sud Lung Transplant Group. J.Cardiovasc.Pharmacol. 1995;25 Suppl 2:S130-S133.
Chapelier A, Reignier J, Mazmanian M, Dulmet E, Libert JM, Dartevelle Pet al.Amelioration of reperfusion injury by pentoxifylline after lung transplantation. The Universite Paris-Sud Lung Transplant Group. J.Heart Lung Transplant. 1995;14:676-83.
Kishi M, Tanaka H, Seiyama A, Takaoka M, Matsuoka T, Yoshioka Tet al.Pentoxifylline attenuates reperfusion injury in skeletal muscle after partial ischemia. Am.J.Physiol 1998;274:-H1435-H1442.
Cao Y, Stafforini DM, Zimmerman GA, McIntyre TM, Prescott SM. Expression of platelets activating factor acetyl hydrolase is transcryptionally regulated by mediator inflamation. J.Biol.Chem. 1998;273:4012-20.
Michael F, Festing W, Altman GD. Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR journal 2002;43:244-58.
Aktan AO, Yalcin AS. Ischemia Reperfusion Injury, Reactive Oxygen Metabolites, and the Surgeon. Turk J Med 1997;28:1-5.
Silver D, Dhar A, Slocum M, Adams JG, Jr., Shukla S. Role of platelet-activating factor in skeletal muscle ischemia-reperfusion injury. Adv.Exp.Med.Biol. 1996;416:217-21.
Shinozaki K, Kawasaki T, Kambayani J, Sakon M, Shiba E, Uemura Yet al.A New Method of purification and sensitive bioassay of PAF in Human whole blood. Life Sci 1994;54:429-37.
Saputra A. Pengaruh pemberian pentoxifylline terhadap perubahan histopatologi pada cidera iskemik-reperfusi tungkai akut. Fakultas Kedokteran Universitas Indonesia 2005.
Heriansyah T. Pengaruh pemberiaan pentoxifylline terhadap perubahan kadar Tumor necrotic factor alpha pada cidera iskemik-reperfusi tungkai akut. Fakultas Kedokteran Universitas Indonesia. 2005.
Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc.Surg. 2002;10:620-30.
Defraigne JO, Pincemail J. Local and systemic consequences of severe ischemia and reperfusion of the skeletal muscle. Physiopathology and prevention. Acta Chir Belg. 1998;98:176-86.
Matuschak GM. Multi Organ system Failure : Clinal Expression, Phatogenesis, and Therapy, In: Tak PP, Firestein GM, editors. General Management of Patient. New York: Springer-Verlag;2001. p. 221-47.
Coe DA, Freischlag JA, Johnson D, Mudaliar JH, Kosciesza SA, Traul DKet al.Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury. J.Surg.Res. 1997;67:21-25.
Odeh M. The role of reperfusion-induced injury in the pathogenesis of the crush syndrome. N.Engl.J Med 1991;324:1417-22.
Kishi M, Tanaka H, Seiyama A, Takaoka M, Matsuoka T, Yoshioka Tet al.Pentoxifylline attenuates reperfusion injury in skeletal muscle after partial ischemia. Am.J.Physiol 1998;274:H1435-H1442.
Zimmerman GA, McIntyre TM, Prescott SM, Stafforini DM. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med 2002;30:S294-S301.
Montrucchio G, Alloatti G, Camussi G. Role of platelet-activating factor in cardiovascular pathophysiology. Physiol Rev. 2000;80:1669-99.
Adams JG, Jr., Dhar A, Shukla SD, Silver D. Effect of pentoxifylline on tissue injury and platelet-activating factor production during ischemia-reperfusion injury. J.Vasc.Surg. 1995;21:742-48.
Silver D, Dhar A, Slocum M, Adams JG, Jr., Shukla S. Role of platelet-activating factor in skeletal muscle ischemia-reperfusion injury. Adv.Exp.Med.Biol. 1996; 416:217-21.
Iwai A, Itoh M, Yokoyama Y, Yasue N, Miyamoto T, Joh Tet al.Role of PAF in ischemia-reperfusion injury in the rat stomach. Scand.J.Gastroenterol.Suppl 1989;162: 63-66
Black SC, Driscoll EM, Lucchesi BR. Inhibition of platelet-activating factor fails to limit ischemia and reperfusion-induced myocardial damage. J.Cardiovasc.Pharmacol. 1992;20:997-1005.
Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Br.Med.Bull. 2004;70:71-86.
Clark SC, Rao JN, Flecknell PA, Dark JH. Pentoxifylline is as effective as leukocyte depletion for modulating pulmonary reperfusion injury. J.Thorac.Cardiovasc.Surg. 2003;126:2052-57.
Freitas JP, Filipe PM. Pentoxifylline. A hydroxyl radical scavenger. Biol.Trace Elem.Res. 1995;47:307-11.
Coe DA, Freischlag JA, Johnson D, Mudaliar JH, Kosciesza SA, Traul DKet al.Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury. J Surg.Res. 1997;67:21-25.
Doherty GM, Jensen JC, Alexander HR, Buresh CM, Norton JA. Pentoxifylline suppression of tumor necrosis factor gene transcription. Surgery 1991;110:192-98.
Sullivan GW, Carper HT, Novick WJ, Jr., Mandell GL. Inhibition of the inflammatory action of interleukin-1 and tumor necrosis factor (alpha) on neutrophil function by pentoxifylline. Infect.Immun. 1988;56:1722-29.
Muller JM, Vollmar B, Menger MD. Pentoxifylline reduces venular leukocyte adherence (“reflow paradox”) but not microvascular “no reflow” in hepatic ischemia/reperfusion. J.Surg.Res. 1997;71:1-6.
Chapelier A, Reignier J, Mazmanian M, Detruit H, Dartevelle P, Parquin Fet al.Pentoxifylline and lung ischemia-reperfusion injury: application to lung trans-plantation. Universite Paris-Sud Lung Transplant Group. J.Cardiovasc.Pharmacol. 1995;25 Suppl 2:S130-S133.
Chapelier A, Reignier J, Mazmanian M, Dulmet E, Libert JM, Dartevelle Pet al.Amelioration of reperfusion injury by pentoxifylline after lung transplantation. The Universite Paris-Sud Lung Transplant Group. J.Heart Lung Transplant. 1995;14:676-83.
Kishi M, Tanaka H, Seiyama A, Takaoka M, Matsuoka T, Yoshioka Tet al.Pentoxifylline attenuates reperfusion injury in skeletal muscle after partial ischemia. Am.J.Physiol 1998;274:-H1435-H1442.
Cao Y, Stafforini DM, Zimmerman GA, McIntyre TM, Prescott SM. Expression of platelets activating factor acetyl hydrolase is transcryptionally regulated by mediator inflamation. J.Biol.Chem. 1998;273:4012-20.
Michael F, Festing W, Altman GD. Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR journal 2002;43:244-58.
Aktan AO, Yalcin AS. Ischemia Reperfusion Injury, Reactive Oxygen Metabolites, and the Surgeon. Turk J Med 1997;28:1-5.
Silver D, Dhar A, Slocum M, Adams JG, Jr., Shukla S. Role of platelet-activating factor in skeletal muscle ischemia-reperfusion injury. Adv.Exp.Med.Biol. 1996;416:217-21.
Shinozaki K, Kawasaki T, Kambayani J, Sakon M, Shiba E, Uemura Yet al.A New Method of purification and sensitive bioassay of PAF in Human whole blood. Life Sci 1994;54:429-37.
Saputra A. Pengaruh pemberian pentoxifylline terhadap perubahan histopatologi pada cidera iskemik-reperfusi tungkai akut. Fakultas Kedokteran Universitas Indonesia 2005.
Heriansyah T. Pengaruh pemberiaan pentoxifylline terhadap perubahan kadar Tumor necrotic factor alpha pada cidera iskemik-reperfusi tungkai akut. Fakultas Kedokteran Universitas Indonesia. 2005.
Views & Downloads
Abstract views: 3399
PDF (Bahasa Indonesia) downloads: 2236
PDF (Bahasa Indonesia) downloads: 2236
How to Cite
Juzar, D., Kasim, M., Hersunarti, N., & Kaligis, R. (1). Effect of Pentoxifylline on Platelet - Activating Factor Production in Acute Limb Ischemic - Reperfusion Injury. Indonesian Journal of Cardiology, 28(2), 93-99. https://doi.org/10.30701/ijc.v28i2.252
Section
Clinical Research
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
