Effects Of Levosimendan On Renal Function In Patients Undergoing Coronary Artery Surgery With Low

Acute kidney injury (AKI) is a serious complication of cardiac operation, the incidence rate of over30%after heart operation. Causes of AKI in perioperation period is multifactorial including the basic situation of patient and the operation process. A retrospective analysis points out, many factors could increase the incidence of AKI during perioperative period, including the patient’s age, previous history of chronic renal insufficiency, chronic heart failure, the use of intra aortic balloon counterpulsation, poor blood, emergency operation, blood products in large quantities time and again, extracorporeal circulation operation, ect. At the same time, those in the operation, such as drug use, operation injury, low blood perfusion of the kidney, tissue reperfusion injury, toxin, inflammatory cytokines, immune response, could also damage the kidney function. Acute renal failure after cardiac operation means a significantly increased mortality during perioperative period. Follow-up studies have confirmed, AKI after heart operation could not only effect the early recovery after operation, but also increase the long-term mortality. The cardiac operation with cardiac insufficiency is one of the most important factors in the incidence of acute renal insufficiency after operation. For this kind of patients better organ protection, especially renal protectin, is the hotspot and the focus of current research in the development of cardiac surgery.Levosimendan is the first listed species to a new generation of cardiotonic drugs-calcium sensitizer, mainly used in the clinical treatment of various acute heart failure disease. This kind of medicine mainly by increasing the sensitivity of myocardial contractile protein on Ca2+, to achieve the purpose of increasing myocardial contractility, which is called calciumsensitizer. The drug was developed by the company Lyon (Orion) in Finland, in2000October for the first time listed on market in Sweden. Clinical studies show that, as a sensitizer, levosimendan improve heart function through the mechanism of positive inotropic drugs without increasing intracellular calcium concentration, heart rate and myocardial oxygen consumption; Through activation of K+channel, LS could dialte the coronary artery and supply more myocardial oxygen. LS could improve myocardial function of left ventricular dysfunction and percutaneous coronary intervention treatment of postoperative myocardial stunning. Studies shown that the use of catecholamines and LS can play a positive inotropic effect and protective effect on the heart in the severe coronary heart disease after CABG operation.Animal experiments pointed out, LS could increase the perfusion flow of the kidney and has a protective effect on impaired renal function. In the clinical trials, LS has a protective effect for patients with congestive heart failure on kidney function. LS can reduce the incidence rate of acute renal insufficiency and increase the force of cardiac contraction and expansion of blood vessels in peripheral and renal artery. Renal protective effect in cardiac operation of LS are still lack of clinical data and there are also some disputes. The the renal protective effect of LS during coronary artery bypass grafting operation need further study to confirm.Objective:The purpose of our study is to evaluate the protective effects of LS on renal function during CABG procedure under the condition of decreased cardiac ejection fraction. For the CABG operation with left ventricular dysfunction, the application of LS might improve both cardiac systolic function and the renal protective effect.Methods: 1. The clinical research belong to the randomized double blind study prospective. The object of study and group:since May2010, selected40cases were divided into treatment group and control group (each20cases). Inclusion criteria:age55to75years old, ECG ischemic changes, or positive exercise test, coronary angiography showed stenosis>70%, grade of angina pectoris (Canadian Association of cardiovascular disease, heart function grading) level3(NYHA) II-III. Left ventricular ejection fraction (eject fraction, EF) less than45%and30%, a single CABG in patients undergoing elective operation.Exclusion criteria:Patients with cerebral vascular disease; the blood system diseases; the hepatic, renal insufficiency; myocardial infarction in the recent (less than1month), reoperation; patients with acute myocardial infarction or patients with cardiogenic shock, and with a valve or intracardiac malformation were excluded in the study, patients with application of intra aortic balloon counterpulsation (IABP) assisted; the abnormal mental patient.All patients were diagnosis by coronary angiography. Gender, age, preoperative heart function evaluated by doppler echocardiography and NYHA grading packet without obvious difference. Two groups of patients were performed by the same surgical group.2. methods of administration:The basic treatment was same in treatment group and experimental group. LS was used in the treatment group additionally. The initial loading dose of LS was10μg/kg with the injection time of10min, then continously intravenous infusion at the speed of0.1-0.2μg/(kg·min) for23h.3. operation processWhen the Patient got into the operation room, routine monitoring was done, such as electrocardiogram, heart rate, respiratory rate, pulse oxygen saturation and nasal temperature, rectal temperature. After standard anesthesia, the left radial artery was cannulated to monitor arterial blood pressure, and the right internal jugular vein was catheterizated to monitor central venous pressure. After regular disinfection, a single iscion with median sternotomy was done, The left internal mammary artery and the great saphenous vein were harvested as the bypass graft. At first the left internal mammary artery was anastomosed with left anterior descending artery, then the great saphenous veins were anastomosed with the ascending aorta. Side wall holes punched in the ascending aorta after sidely clamp, and saphenous vein were anatomosed with aorta holes by the use of continuous6-0prolene suture.Exposure method Target vesseld were exposed by the use of the myocardial fixation (Octopus). If necessary, the hollow shunt was placed in coronary artery. Distal anastomosis of saphenous vein with target vessel were done by using7-0prolene suture; Left anterior descending arterty is the first anatomosis and the most severe lesion vessel is next target for anastomosis. The anastomosis were check to aviod the blood leak. The pericardium was sutured and the protamine was used to neutralize heparin. The pericardial mediastinal drainage tube were placed and chest was closed at the end of operation. After coronary artery bypass grafting, the patients accepted routine treatment.4. renal function test:By selecting the sensitive indicator of early renal damage, including serum Cystatin C concentration, urinary N-acetyl-Glucosaminidase(UNAG) concentration, and computing the glomerular filtration rate (GFR), the renal function were measured in the peri operation period of multi points to assess the protective effect assessment of LS.The serum creatinine concentration, plasma Cystatin C were measured at the time point of before the operation,6h the1st,2nd and5th day morning after the operation; Glomerular clearance rates were calculated with creatinine concentration. UNAG were measured at the time point before operation,6h and24h after operation.5. tatistical analysisThe results data were indicated with mean±standard deviation. SPSS17.0statistical software were used to statistical process. The t test for measurement data and chi square test for count data were used to do the statistical comparation between groups. The difference has statistical significance with p<0.05.Results:After the operation the serum creatinine concentration were gradually increased, reached a peak in3days after operation and then decreased gradually in both the experimental group and the control group. Two groups of patients after operation at each time point serum creatinine concentration had no obvious difference. According to standard definition of renal dysfunction with creatinine index increased25%more than basic indicators, early renal dysfunction rate in two groups of patients after operation has no obvious difference.After operation glomerular clearance rate has gradually increased in both experimental group and control group, which reached a peak in3days after operation and then decreased gradually. GFR in LS group-was higher than the control group in the second day after the operation. No significant difference was found in other timepoint. According to definition of renal dysfunction with glomerular filtration rate lower than70ml/(min.1.73m2),3patients in the LS group were with renal dysfuncionfunction, and6patients in the control group. Acute kidney dysfunction failure rate is lower in the LS group than in the control group.After the detection of serum Cystatin C concentration, serum concentrations of two groups were rising in the first three days after operation and recovered gradually. Cystatin C increased earlier than serum creatinine. Cystatin C concentration in group LS was lower in the first and second day than that of the control group with statistical significance (P<0.05). The patients in LS group suffered less kidney injury than that in the control group in early period after operation.Urinary N-acetyl-glucosaminidase (N-acetyl-glucosaminidase, UNAG) level reached a peak at6h after operation and return to the preoperative level after24h. There are early kidney damage mainly exists in the6h after the operation.The patients in LS group suffered less renal injury than that in the control group in early period after operation. According to the measurement of NAG and Cystatin C, it was suggested that there were renal impairment in coronary artery bypass graft after operation. The Cystatin C and NAG in the early postoperative period is more sensitive than the creatinine. Levosimendan is safe for renal function without increasing renal function impairment.Conclusion:Acute renal insufficiency exists in coronary artery bypass grafting operation with decreased cardiac systolic function. LS may reduce the renal damage and provide enal protection. The specific protection mechanisms need to be further confirmed experimentally.Meaning:With the aging society coming and the improvement of coronary heart disease treatment, the severity of CHD to receive coronary artery bypass graft operation was obviously improved. Some patients had suffered a repeated process of serious myocardial ischemia and the myocardial systolic function has declined and cardiac dysfunction existed before the operation. Heart dysfunction perioperative is an important risk factor of the incidence of severe renal insufficiency. Levosimendan, as a calcium sensitizer through the mechanism of positive inotropic drugs, is different from the traditional vasodilator, which can improve the renal perfusion periopertively. Our study suggests that LS could reduce the degree of kidney injury during coronary bypass operation in perioperative period, which could likely improve the safety of operation and reduce the incidence of the operation complications.