Study On The Effect Of Ulinastatin On CRP And T-lymphocyte Subsets And Cardiac Functional Indexs In Patients With Chronic Heart Failure

BackgroundIt is well known to all that chronic heart failure (CHF) is one of the main consequences of many cardiovascular diseases. Though in the past twenty years the prognosis in patients with CHF was improved due to the improvement of drug treatments and other interventions, the mortality, morbidity and readmission was still high. Recently medical workers realized that CHF involves immune activation. There is now more and more evidence to show that inflammatory response plays an important role in the complex pathophysiology of CHF, with proinflammatory cytokines such as C-reactive protein (CRP), tumor necrosis factor-a (TNF-α), interleukin-1, interleukin-6, monocyte chemoattractant protein-1 et al, overexpression both in the systemic circulation and locally in the falling myocardium. Sustained overexpression of inflammatory mediators contribute to inducibility to cardiomyocyte apotosis, fibrosis in myocardial extracellular matrix, promotion of myocardial remodeling, and link to the development and progression of the system of CHF. Additionally, elevated plasm level of proinflammatory cytokines is positive relation to severity degree of CHF, and results in a poor prognosis in patients with CHF. So we presume that anti-inflammatory intervention in heart failure will be a new and promising therapeutic approach for patients with CHF.But 2 large scale clinical trials (RENAISSANCE and RECOVER) for antagonizing TNF-αtherapy in patients with CHF have been prematurely terminated due to the disappointing outcome. The results told us that inhibition of inflammatory proesses contributing to the progression of CHF is difficult and challenging. As far as our understanding and proofs supported by a variety of trials, a complex immune mechanism is involved in the pathophysiology in CHF. We consider that activated inflammatory mediators in CHF form a complex network. Therefore, the benefit of antagonizing only one cytokine in this network may be diminished by the interaction of other factors in the network. We presume that a more generalized therapy targeting this network may produce certain beneficial effects in patients with CHF. Ulinastatin is a broad-spectrum protease inhibitor that is purified from the fresh urine of healthy men, and it can suppress the activity of lots of protease. In addition, ulinastatin have anti-inflammation activity such as inhibiting the release of cytokines and reduce the infilitration of the leukocyte. It has recently been reported that ulinastatin attenuated ischemia-reperfusion injury through its cytoprotection action. There is abnormal immune activation in patients with CHF associated with imbalance of T-lymphocyte subsets. Reportedly, ulinastatin have immunomodulation function and improve immune condition. So we hypotheses that ulinastatin may be a selective therapeutic approach for patients with CHF, and provide additional benefit in result of its improving immune condition and clinical indices.We provided the addition of ulinastatin to conventional therapy for patients with CHF in this study, to observe the change in the plasm T-lymphocyte subsets, CRP, as well as clincal indices before and after seven days. The aim was to investigate the effect of ulinastatin on plasm T-lymphocyte subsets, inflammatory mediator and assess its effect on cardiac functional index in patients with CHF,and to provide the experimental and theoretical evidence supporting anti-inflammatory therapy in CHF, also to explore the effective anti-inflammatory drug.Subjects and methods1. study population: the study included 63 inhospital patients with CHF from department of cardiology, daping hospital of third military medical university, and age range from 33 to 77 years old, with mean age 65.6±9.9 years old (28male and 35 female). CHF was diagnosed according to Framingham criterion. The etiology of CHF was from coronary heart disease (CHD) (n=24), hypertension (n=18), idiopathic dilated cardiomyopathy (IDCM) (n=8), or valvular heart disease (VHD) (n=13), and the New York Heart Association (NYHA) functional class is fromⅡ(n=14),Ⅲ(n=34), orⅣ(n=15).2. methods: 63 patients receiving conventional treatment were randomly allocated to either ulinastatin group ( 105 unit per day, n=31) or conventional treatment group ( n=32 ). To observe the change in the plasm C-reactive protein (CRP), T-lymphocyte subsets, as well as the change of the condition of the heart failure score (HFS), New York Heart Association (NYHA) function class, 6-minute walk test distance, brain natriuretic peptide (BNP) level, in patients with CHF before and after the seven-day′s treatment. Results1. 61 patients finished the study, apart from 1 in the ulinastatin group and 1 in conventional treatment group dead. There were no stastifical differences in baseline characteristics between 2 groups.2. After 7 days'treatment there was a significant reduction in the circulating level of CRP in both the two groups. Furthermore, significant improvements in NYHA functional class, 6-minute walk test distance (m), BNP level as well as HFS were observed in both the two groups at 7 days compared with baseline. .3. Ulinastatin elevated the levels of CD4 T cell and ratio of CD4/CD8 T cell, conversely, decreased significantly the concentration of CRP compared with the conventional treatment group at 7th day. But there were no obvious differences in NYHA functional class, 6-minute walk test distance (m), HFS and BNP between the two groups after 7 days'treatment.Conclusion1. These data suggest that the addition of ulinastatin to the conventional treatment for CHF patients can improve the immune condition and reduce the inflammatory response.2. We did not find any improvement in NYHA functional class, 6-minute walk test distance (m), HFS and BNP level in Ulinastatin group compared with conventional treatment group.