Effect of Iloprost, a Prostacyclin Analogue, on Myocardial Ischemia- Reperfusion Injury
Abstract
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 postoperative prognosis.
This study was conducted to assess the effect that iloprost, a prostacyclin 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 by using the modified Langendorff perfusion apparatus to form control (n = 10) and experimental study groups (n = 10). Following a preischemic period of perfusion and an ischemic period of 20 minutes, control hearts were perfused with Krebs–Henseleit solution. In the experimental group, iloprost
(0.45 µg/kg per hour) was included in the perfusates for the last 10 minutes of the preischemic phase. Following cardiac stabilization, heart rate (pulse/min), contractility (mm), and aortic pressure (mmHg) values were recorded at the end of preischemia, postischemia, and reperfusion. 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.
References
Ambrosio G, Villari B, Chiariello M. 1992. Calcium antagonists and experimental myocardial ischemia reperfusion injury. J Cardiovasc Pharmacol 20(suppl 7):S26-9.
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.
Cui J, Das DK, Bertelli A, Tosaki A. 2003. Effects of L-carnitine and its derivatives on postischemic cardiac function, ventricular fibrillation and necrotic and apoptotic cardiomyocyte death in isolated rat hearts. Mol Cell Biochem 254(1-2):227-34.
Das DK, Engelman RM, Rousou JA, Breyer RH, Otani H, Lemeshow S. 1986. Pathophysiology of superoxide radical as potential mediator of reperfusion injury in pig heart. Basic Res Cardiol 81(2):155-66.
Ding YF, Li YL, Ho SY. 1996. [Ischemic preconditioning and exogenous L-arginine reduce infarct size in rabbit heart]. Sheng Li Xue Bao 48(6):564-70. Chinese.
Edmunds LH Jr. 2002. The evolution of cardiopulmonary bypass: lessons to be learned. Perfusion 17(4):243-51.
Flynn JD, Akers WS. 2003. Effects of the angiotensin II subtype 1 receptor antagonist losartan on functional recovery of ısolated rat hearts undergoing global myocardial ıschemia-reperfusion. Pharmacotherapy 23(11):1401-10.
Forman MB, Virmani R, Puett DW. 1990. Mechanisms and therapy of myocardial reperfusion injury. Circulation 81(3 suppl):IV69-78.
Gardner TJ, Stewart JR, Casale AS, Downey JM, Chambers DE. 1983. Reduction of myocardial ischemic injury with oxygen-derived free radical scavengers. Surgery 94(3):423-7.
Knezl V, Sotniková R, Okruhlicová L, Navarová J. 1999. Effect of stobadine on cardiac injury induced by ischemia and reperfusion. Life Sci 65(18-19):1931-3.
Kurtel H, Granger DN, Tso P, Grisham MB. 1992. Vulnerability of intestinal interstitial fluid to oxidant stress. Am J Physiol 263(4 Pt 1):G573-8.
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 Res 72(2):403-12.
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.
Pucheu S, Coudray C, Tresallet N, Favier A, de Leiris J. 1993. Effect of iron overload in the isolated ischemic and reperfused rat heart. Cardiovasc Drugs Ther 7(4):701-11.
Qiu Y, Galiñanes M, Hearse DJ. 1995. Protective effect of nicorandil as an additive to the solution for continous warm cardioplegia. J Thorac Cardiovasc Surg 110(4 Pt 1):1063-72.
Saeed SA, Waqar MA, Zubairi AJ, et al. 2005. Myocardial ischaemia and reperfusion injury: reactive oxygen species and the role of neutrophil. J Coll Physicians Surg Pak 15(8):507-14.
Simpson PJ, Mickelson J, Fantone JC, Gallagher KP, Lucchesi BR. 1987. Iloprost inhibits neutrophil function in vitro and in vivo and limits experimental infarct size in canine heart. Circ Res 60(5):666-73.
Sinclair AJ, Barnett AH, Lunec J. 1990. Free radicals and antioxidant systems in health and disease. Br J Hosp Med 43(5):334-44.
Swedberg K, Hed P, Wadenvik H, Kutti J. 1987. Central haemodynamic and antiplatelet effects of iloprost--a new prostacyclin analogue--in acute myocardial infarction in man. Eur Heart J 8(4):362-8.
Turan B, Saini HK, Zhang M, Prajapati D, Elimban V, Dhalla NS. 2005. Selenium improves cardiac function by attenuating the activation of NF-κB due to ischemia–reperfusion ınjury. Antioxid Redox Signal 7(9-10):1388-97.
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