EFFECT OF ILOPROST, A PROSTACYCLINE ANALOGUE, ON MYOCARDIAL ISCHEMIA-REPERFUSION INJURY
Myocardial ischemia-reperfusion injury continues to be observed during open heart surgery. Various experimental models have been developed to overcome this injury and to increase postopreative prognosis.
This study was conducted to assess the effect that iloprost, a prostacycline analogue, can have on myocardial ischemia-reperfusion injury. We evaluated tissue damage by measuring the levels of malonyldialdehyde (MDA), glutathione, and nitric oxide (NO) in tissue and perfusates.
In this study, 20 guinea pig hearts were prepared using the modified Langendorf perfusion apparatus to form control (n=10) and experimental study groups (n=10). Following a pre-ischemic period of perfusion and an ischemic period of 20 minutes, control hearts were perfused with Krebs Hanseleit solution. In the experimental group, iloprost (0.45 mg/kg/hour) was included in the perfusates for the last 10 minutes of the preischemic phase. Following cardiac stabilization, heart rate (pulse/minute), contractility (mm), and aortic pressure (mmHg) values were recorded at the end of pre-ischemia, post-ischemia and reperfusion periods. Perfusate and tissue analyses for glutathione, MDA, and NO levels were made in each group at the end of experiments.
Iloprost was found to have protective effects against myocardial ischemia by means of increased myocardial contractility, decreased tissue/perfusate glutathione levels and inhibited rise of tissue/perfusate MDA observed in the “iloprost-treated” experimental group. Future investigations on myocardial ischemia-reperfusion injury must evaluate iloprost-related mechanisms.
Short Title: Iloprost and ischemia – reperfusion injury
Subject Codes : Iloprost, ischemia and reperfusion injury, glutathione, MDA, NO
-Edmunds LH Jr. (2002). The evolution of cardiopulmonary bypass : lessons to be learned. Perfusion 17 (4): 243-51.
-Forman MB, Virmani R, Puett DW. (1990) Mechanisms and therapy of myocardial reperfusion injury. Circulation (81 3 Suppl): IV69-78.
-Gardner TJ, Stewart R, Casale, AS Downey, JM Chambers. (1983)Reduction of myocardial ischemic injury with oxygen-derived free radical scavengers. Surgery 94(3): 423-27.
- Das DK, Engelman RM, Rousou JA, Breyer RH, Otani H, Lemeshow S.(1986). Pathophysiology of superoxide radical; a potential mediator of reperfusion injury in pig hearts. Basic Res Cardiol 81(2): 155-66.
- Simpson PJ, Mickelson J, Fantone JC, Gallagher KP, Lucchesi Br.(1987). Sustained myocardial protection by iloprost with prolonged infusion in a canine model of temporary regional ischaemia. Fed Proc 46: 1144.
-Kurtel H, Granger DN, Tso P, Grisham MB. (1992). Vulnerability of intestinal interstitial fluid to oxidant stress. Am J Phy 263 (4 Pt1); Q 573-8.
-Nakanishi K, Inoue M, Sugawara E, Sano S. (1997). Ischemic and reperfusion injury of cyanotic myocardium in chronic hypoxic rat model: Changes in cyanotic myocardial antioxidant system. J Thorac Cardiovasc Surg 114(6): 1088-96.
-Swedberg K, Hed P, Wadenvik H, Kutti J. (1987). Central hemodynamic and antiplatelet effects of iloprost-a new prostacyclin analogue-in acute myocardial infarction in man. Eur Heart J 8(4): 362-68.
-Sinclair AJ, Barnett AH, Lunec J. (1990). Free radicals and antioxidant systems in health and disease. Br J Hosp Med 43(5): 334-44.
-Blaustein A, Deneke SM, Stolz RI, Baxter D, Healey N, Fanburg BL. (1989). Myocardial glutathione depletion impairs recovery after short periods of ischemia. Circulation 80(5): 1449-57.
-Ma XL, Weyrich AS, Lefer DJ, Lefer AM. (1993). Diminshed basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium. Circ Research 72(2): 403-12.
- Sheikh Arshad Saeed, Muhammad Anwar Waqar, Akbar Jaleel Zubairi, Hadi Bhurgri, Abdullah Khan, Saqib Ali Sikander Gowani, Saima N. Waqar, M. Iqbal Choudhary, Saima Jalil, Ali Hyder Zaidi, Iffat Ara.(2005). Myocardial ischaemia and reperfusion injury : Reactive oxygen species and the role of neutrophil. JCPSP 15(8 ): 507-514.
- Jeremy D. Flynn, Wendell S. Akers . (2003) Effects of the Angiotensin II Subtype 1 Receptor Antagonist Losartan on Functional Recovery of Isolated Rat Hearts Undergoing Global Myocardial Ischemia-Reperfusion. Pharmacotherapy 23 (11) :1401-1410.
-Turan Belma, Harjot K. Saini, Ming Zhang, Dashang Prajapati, Vijayan Elimban, Naranjan S. Dhalla. (2005). Selenium Improves Cardiac Function by Attenuating the Activation of NF- B Due to Ischemia Reperfusion Injury. Antioxid. Redox Signal 7 (9-10 ): 1388-1397.
- S Pucheu, C Coudray, N Tresallet, A Favier J de Leiris. (1993). Effect of iron overload in the isolated ischemic and reperfused rat heart. Cardiovascular Drugs and Therapy (Historical Archive)( 7 ) ; 4, 701-711.
- Ding YF, Li YL, Ho SY.(1996). Ischemic preconditioning and exogenous L-arginine reduce infarct size in rabbit heart ( Abstract ). Sheng Li Xue Bao 48 ( 6 ):564-70.
- Ambrosio G, Villari B, Chiariello M. (1992). Calcium antagonists and experimental myocardial ischemia reperfusion injury. J Cardiovasc Pharmacol.;20 Suppl 7: S26-9.
-Y. Qiu, M. Galinanes, D. J. Hearse. (1995). Protective effect of Nicorandil as an additive to the solution for continous warm cardioplegia. J. Thorac. Cardiovasc. Surg. (October 1) 110(4): 1063 - 1072.
Author Disclosure & Copyright Transfer Agreement
In order to publish the original work of another person(s), The Heart Surgery Forum® must receive an acknowledgment of the Author Agreement and Copyright Transfer Statement transferring to Forum Multimedia Publishing, L.L.C., a subsidiary of Carden Jennings Publishing Co., Ltd. the exclusive rights to print and distribute the author(s) work in all media forms. Failure to check Copyright Transfer agreement box below will delay publication of the manuscript.
A current form follows:
The author(s) hereby transfer(s), assign(s), or otherwise convey(s) all copyright ownership of the manuscript submitted to Forum Multimedia Publishing, LLC (Publisher). The copyright transfer covers the exclusive rights to reproduce and distribute the article and the material contained therein throughout the world in all languages and in all media of expression now known or later developed, including but not limited to reprints, photographic reproduction, microfilm, electronic data processing (including programming, storage, and transmission to other electronic data record(s), or any other reproductions of similar nature), and translations.
However, Publisher grants back to the author(s) the following:
- The right to make and distribute copies of all or part of this work for use of the author(s) in teaching;
- The right to use, after publication in The Heart Surgery Forum, all or part of the material from this work in a book by the author(s), or in a collection of work by the author(s);
- The royalty-free right to make copies of this work for internal distribution within the institution/company that employs the author(s) subject to the provisions below for a work-made-for-hire;
- The right to use figures and tables from this work, and up to 250 words of text, for any purpose;
- The right to make oral presentations of material from this work.
Publisher reserves the right to grant or refuse permission to third parties to republish all or part of the article or translations thereof. To republish, such third parties must obtain written permission from the Publisher. (This is in accordance with the Copyright Statute, United States Code, Title 17. Exception: If all authors were bona fide officers or employees of the U.S. Government at the time the paper was prepared, the work is a “work of the US Government” (prepared by an officer or employee of the US Government as part of official duties), and therefore is not subject to US copyright; such exception should be indicated on signature lines. If this work was prepared under US Government contract or grant, the US Government may reproduce, royalty-free, all or portions of this work and may authorize others to do so, for official US Government purposes only, if the US Government contract or grant so requires.
I have participated in the conception and design of this work and in the writing of the manuscript and take public responsibility for it. Neither this manuscript nor one with substantially similar content under my authorship has been published, has been submitted for publication elsewhere, or will be submitted for publication elsewhere while under consideration by The Heart Surgery Forum, except as described in an attachment. I have reviewed this manuscript (original version) and approve its submission. If I am listed above as corresponding author, I will provide all authors with information regarding this manuscript and will obtain their approval before submitting any revision. I attest to the validity, accuracy, and legitimacy of the content of the manuscript and understand that Publisher assumes no responsibility for the validity, accuracy, and legitimacy of its content. I warrant that this manuscript is original with me and that I have full power to make this Agreement. I warrant that it contains no matter that is libelous or otherwise unlawful or that invades individual privacy or infringes any copyright or other proprietary right. I agree to indemnify and hold Publisher harmless of and from any claim made against Publisher that relates to or arises out of the publication of the manuscript and agree that this indemnification shall include payment of all costs and expenses relating to the defense of any such claim, including all reasonable attorney’s fees.
I warrant that I have no financial interest in the drugs, devices, or procedures described in the manuscript (except as disclosed in the attached statement).
I state that the institutional Human Subjects Committee and/or the Ethics Committee approved the clinical protocol reported in this manuscript for the use of experimental techniques, drugs, or devices in human subjects and appropriate informed consent documents were utilized.
Furthermore, I state that any and all animals used for experimental purposes received humane care in USDA registered facilities in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH Publication No. 85-23, revised 1985).