The Myocardial Preservation In A Single High Loading Dose Of Statins Therapy Before Coronary Artery Bypass Grafting

Myocardial injury following coronary artery surgeries inevitably takes place.Asymptornatic myocardial injury is assessed by circulating plasma levels of cardiac biomarkers. It is frequent during procedures, and is reported to be associated with operative mortality and cardiac events during follow-up.Therefore, as far as possible to reduce procedure-related myocardial injury, will improve the effect of surgery.HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors, also called statins, were commonly prescribed class of lipid lowering drugs. Many clinical and basic researches have demonstrated that statins may provide beneficial effects outside of reductions in LDL-C and triglycerides. Some cardiovascular benefits of statins precede reduction in plasma cholesterol levels or preexisting atheroma. Statins create many protective effects including decreasing of inflammatory reaction, modulating of endothelial function, decreasing of oxidative stress, stabilizing of atherosclerotic plaque, inhibiting of thrombogenic response, modulating platelet function, against postoperative atrial fibrillation, and so on. This phenomenon is called pleiotropic effects of statins.Statins are commonly and widely used in the prevention of coronary artery disease and its complications. Statins therapy is intensively recommended for the acute coronary syndromes, as well as for the prevention or management of perioperative cardiovascular complications. Studies have shown that preoperative statins administrated could reduce the incidence of myocardial injury after PCI. Recent many obervatinal prospective and retrospective studies demonstrated that a single loading with a high dose of statins therapy could prevent myocaedial damage in PCI. Some small prospective studies repoted that preoperative statins therapy in patients with CAD could reduce the systemic inflammation and the risk of postoperative thrombocytosis and myocardial infarction. Unfortunately, there are not many clinical studies of preoperative statins therapy in cardiac surgery. Moreover, reports of application of an acute loading with a single high dose of statins therapy in coronary artery surgery was more limited.In this thesis, based on clinical observation, we studied the myocardial preservation of a single high loading dose of statins therapy before coronary artery surgery and its mechanisms by biochemistry, molecular biological techniques in clinical cases and the artrial tissues. The results can improve the effect of the coronary surgical treatment, improve patients’ long-term survival, and provide a useful theoretical and clinical basis.Objective:To examine the association between a single hight loading dose of statins before CABG surgery, systemic inflammation and the myocardial damage reflected in level of sensitive and specific biomarkers, to evaluate the safety of a single hight loading dose of statins, and explore its effect on cardiac specific miRNA (miRNA-133a, miRNA-133b, miRNA-208a, miRNA-208b, miRNA-499a-3p, miRNA-499a-5p, miRNA-499b-3p, miRNA-4999-5p, miRNA-1) regulation.Methods:140cases of CABG patients met the inclusion criteria, were randomly divided into two groups:group A--the routine application of statins; group B--12hours before cardiac operation,receiving orally once80mg atorvastatin. Circulating plasma levels of cardiac biomarkers (Troponin T, CK-MB and Myogolbin) were measured on admission (AD), postoperaitive6hours (POH-6), POH-12, POH-24, POH-48, POH-72, POH-96, and POH-120. Blood samples were taken from both groups on2days before operation (PRD-2), postoperative1day (POD-1), POD-4,POD-7and just before dischanger(DIS) for measurement plasma levels of transaminase (ALT and AST), total bilirubin, lipid (LDL-C, TG and TC) and hsCRP. Right atrial was obtained from8patients undergoing CABG (3patients from group B, others5patients from group A). In addition, right atrial from4healthy individuals was obtained from prospective multi-organ donors who did not have cardiovascular pathology in cases in which technical reasons prevented transplantation.The expression of cardiac specific miRNAs including miRNA-1, miRNA-133, miRNA-208, miRNA-499were examined by qRT-PCR.Results:All operations were uneventful. Baseline characteristics of tow groups were similar, no significant difference. Peak values of troponin T, CK-MB, hsCRP were significant decreased in group B compared with group A. Incidences of troponin T and CK-MB greater than99th URL, incidence of troponin T greater than5times above99th URL were much higher in group A than group B. Incidences of ALT and AST greater than3timesabove99th URL normal were similar in bothe groups. Values of ALT, AST, TBIL, TC, TG, LDL-C were no different between two groups postoperative1day. Among the healthy control group, group A and group B, miRNA-1, miRNA-133a, miRNA-133b, miRNA-208a, miRNA-208b, miRNA-499a-3p, miRNA-499a-5p, and miRNA-499b-3p were not significant changed. miRNA-499b-5p was significantly increased in group B comparing to both healthy control group and group B.Conclusion:A preoperative single high loading dose of statins therapy is safe and play a role in myocardial protection and its cardiac protection effect might be related to elevated miRNA-499b-5p.