GW24-e3004 Pitavastatin preconditioning reduces myocardium ischaemia/reperfusion injury through microvascular protection in mice

Objectives To examine whether Pitavastatin Preconditioning could effectively reduce ischaemia/reperfusion injury (IRI) and the underlying mechanisms involved. Methods Ligated the anterior descending coronary artery for 30 minutes and then loosen the ligation for 1 hour to establish ischaemia/reperfusion model in mice. A potent 3-hydroxy-3-methylglutaryl-coenzyme A reductase, pitavastatin was given to the mice as a single dose (5 mg/kg or 10 mg/kg) by gavage 1 hour before reperfusion. Animals were divided into 5 groups (control group, ischaemia group, ischaemia/reperfusion group, pitavastatin 5mg groups and pitavastain 10 mg group). Extravasated Evans blue dye measured by spectrophotometry 30 minutes after reperfusion to assess ischaemia/reperfusion injury (IRI)-induced vascular leakage. We introduced in vivo cryotechnique (IVCT), which immediately cryofixes beating heart tissue of living mice in situ, to measure the heart microvascular reperfusion situation. Results Pitavastatin Preconditioning prevented IRI-induced vascular leakage and improve microvascular blood reflow, decreased the LDH, CK-MB, CRP and immflammatory factors expression (P < 0.05 VS. ischaemia/reperfusion group). The beneficial effects of pitavastatin on preventing microvascular stability may because of it could induce eNOS and Cx43 expression. Conclusions Our results demonstrated that Pitavastatin Preconditioning reduces Myocardium ischaemia/reperfusion injury through Microvascular protection: preventing microvascular endothelial cells dysfunction and improving Cx43 expression.