Effect Of Isoflurane Preconditioning On Myocrdial Gene Expression In Patient Undergoing Cardial Valve Replacement

Objective On the basis of confirmation that myocardial microstructure can be improved as well as plasma level of metrix metalloproteinase(MMP)-9 and von Willebrand factor(vWF) can be decreased by isoflurane preconditioning after surgery in patients undergoing cardiac valves replacement(CVR), myocardial gene expression profiles affected by isoflurane preconditioning were detected with gene microarray, aiming to constructing the framework of related gene expression profiles and revealing the mechanisms of myocardial protection with isoflurane preconditioning and to providing the proper anesthetics usage in CVR surgery patient.Methods Patients with CVR surgery were randomly assigned to receive either isoflurane of 1.0 minimum alveolar concentration end-tidal(1.1%-1.2%) for 30 min followed by a 15-min washout period before the beginning of cardiopulmonary bypass(CPB)(study group) or not(control group). Cardiac function was assessed using a pulmonary artery catheter at the time after anesthetic induction as well as before inhalating isoflurane(T0), at 30 min after aortic clamp opening (T1), closion of thorax (T2), and at 6 h(T3),12 h(T4) and 24 h(T5) after aortic clamp opening, respectively. Blood samples were obtained at the time of To, T1, T3, T4, T5, respectively. Right atrial appendage was sampled for observation of myocardial microstructure and detection of gene expression profiles at the time when catheter of superior vena caval was inserted into precava and when the catheter was extracted respectively. At last, gene expression profiles that obtained in the study was verified with fluorescence quantitative real-time polymerase chain reaction(PCR).Results Comparing with To, in both study and test group, a significant decrease of mean arterial blood pressure (MABP) was detected at T1-T4(P<0.05或P<0.01), a significant decrease of mean pulmonary arterial pressure(PAOP) was detected at T2-T5(P<0.05或P＜0.01), a significant decrease of systemic vascular resistance(SVR) was detected at T1-T5(P<0.05或P<0.01), a significant increase of left ventricular stroke work index(LVSWI), stroke volume(SV) and cardiac output(CO) were detected at T1-T5(P< 0.05 or P<0.01). Still comparing with To, plasma level of MMP-9 increased significantly at T1-T4 in control group and at T1 in study group, respectively. Plasma level of vWF decreased significantly at T1, T4 and T5 in control group and at T1-T5 in study group, respectively. Comparing with control group, PAOP decreased significantly at T5(P<0.05), LVSWI and CO increased significantly at T3-T5 (P<0.05 or P<0.01), SV increased significantly at T4-T5 in study group, and there was a significant decrease with MMP-9 level at T3 and vWF at T1 and T3 in study group(P<0.05) when comparing with control group. Myocardial microstructure was better in study group when comparing with control group. There were total 22 differential expression genes regulated up or down 2 fold or greater than 2 fold in study group when compared with control group detected with gene microarray. Half of these corresponding proteins locate extracellularly or in cell membrane. There were 9 genes that their functions involve in signaling pathways. The function of all these genes mainly involved in signaling pathway, immunity, homeostasis, cell adhesion, extracellular matrix and cell skeleton, apoptosis, oxygen delivery and so on, and the most amount of these genes was involved in signaling pathways. Then,3 of these 22 genes were detected with fluorescence quantitative real-time PCR and its results were coincident to that of gene microarray.Conclusion 1. Cardiac function can be improved by isoflurane preconditioning in 24 h of CVR surgery patient.2. Plasma level of MMP-9 and vWF can be decreased by isoflurane preconditioning in 6 h of CVR surgery patient.3. Myocardial microstructure can be improved by isoflurane preconditioning in CVR surgery patient.4. Myocardial gene expression profiles can be altered by isoflurane preconditioning in CVR surgery patient which maybe principally involved in signaling pathway, immunity, homeostasis, cell adhesion, extracellular matrix and cell skeleton, apoptosis, oxygen delivery and so on.