P167Simvastatin & irbesartan suppresses inflammatory responses, chemokine expressions and apoptosis induced by myocardial ischemia/reperfusion in male rats

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Abstract

Background: 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.

Objective: This study was undertaken to investigate the potential role of simvastatin and Irbesartan in amelioration of myocardial I/R injury induced by ligation of left anterior descending coronary artery rat model.

Material & methods : The rats were randomized into 5 equal groups. Group 1 sham group, rat underwent the same anesthetic and surgical procedure as the control group except for ligation of LAD , group 2 control group, rats underwent ligation for LAD and subjected to regional ischemia for 25 min and reperfusion for 2 hours, group 3 control vehicle , rats underwent ligation for LAD and received Irbesartan and simvastatin vehicle (normal saline), group 4 rat pretreated with Irbesartan 3mg/kg i.p.30 minuts before LAD ligation, group 5 rat pretreated with simvastatin 1mg/kg i.p 1 hr before LAD ligation , the LAD is then transiently ligated using a 6-0 prolene suture for a 25-minute ischemia reperfusion was initiated by releasing ligature. 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). The heart were harvested, the apical side was fixed in 10% formalin for histological examination and apoptosis study , the basal side was homogenized for the measurement of tissue tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) , interleukin -6 (IL-6),Monocyte chemottractant protein -1 (MCP-1) and Macrophage inflammatory protein (MIP-1 alpha).

Results: 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.further more all rats in control group showed significant (p<0.05) apoptosis. Both Irbesartan and simvastatin significantly counteract the increase in myocardium level of TNF-α, IL-1B,IL-6,MCP-1,MIP-1alpha,plasma cTnI & apoptotic (P < 0.05). histological analysis revealed that both Irbesartan and simvastatin markedly reduced (P < 0.05) the severity of heart injury in the rats underwent LAD ligation procedure.

Conclusion: The results of the present study reveal that Irbesartan and simvastatin may ameliorate myocardial I/R injury in rats via interfering with inflammatory reactions & apoptosis which induced by I/R injury.

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