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Myocardial ischemia–reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Injury of myocardium due to ischemia–reperfusion includes cardiac contractile dysfunction, arrhythmias as well as irreversible myocytes damage. These changes are considered to be the consequence of imbalance between the formation of oxidants and the availability of endogenous antioxidants in the heart.
This study was undertaken to investigate the potential role of Irbesartan in amelioration of myocardial I/R injury induced by ligation of coronary artery in a rat model.
Materials & Methods
Adult male Swiss Albino rats were randomized into 4 equal groups. Group (1) sham group: rats underwent the same anesthetic and surgical procedure as the control group except ligation of LAD coronary artery, Group (2) control group: rats subjected to regional ischemia for 25 min and reperfusion for 2 hours by ligation of LAD coronary artery, Group (3) control vehicle group: rats received vehicle of Irbesartan (normal saline) via I.P injection and subjected to regional ischemia for 25 min and reperfusion for 2 hours by ligation of LAD coronary artery, Group (4) Irbesartan treated group:rats pretreated with Irbesartan 3mg/kg i.p. 30 minutes before ligation of LAD coronary artery. At the end of experiment (2 hr of reperfusion), blood samples were collected from the heart for measurement of plasma level of cardiac troponin I(cTn I). after that the heart was harvested and divided in to 3 parts, one part was used for measurement of SSDNA (a marker for apoptosis) and another part was homogenized for the measurement of tissue tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and interleukin-6,Monocyte chemo attractant protein-1 and Macrophage inflammatory protein -1α and the last part for histopathology study.
Compared with the sham group, levels of myocardial TNF-α & IL-1β, IL-6, MCP-1. MIP-1alpha; plasma cTn I were increased (p<0.05). Histologically,all rats in control group showed significant (p<0.05) cardiac injury. Furthermore all rats in control group showed significant (p<0.05) apoptosis. Irbesartan significantly counteract the increase in myocardium level of TNF-α, IL-1B, IL-6, MCP-1, MIP-1alpha, plasma cTnI& SSDNA apoptotic marker (p<0.05). Histological analysis revealed that Irbesartan markedly reduced (p<0.05) the severity of heart injury in the rats underwent LAD ligation procedure.
The results of the present study reveal that Irbesartan may ameliorate myocardial I/R injury in rats via interfering with inflammatory reactions & apoptosis which induced by I/R injury.