| Objective and Background Shock heart (cardiac shock) in early stage of severe burn patients has been found in recent years. It causes not only cardiac insufficiency, but also aggravates shock. It is one of the important factors leading to hypoxic and ischemic damages and dysfunctions in other organs. Therefore, to prevent and treat shock heart in early burn patients is of clinical importance. Previous studies confirmed that uncontrollable inflammatory response is one of the main pathogenesis of shock heart. However, no effective method has been found to control the response. Ulinastatin, a multivalent enzyme inhibitor, represents the first ethical drug using purified from human urine. It has widely roles in many aspects, including alleviating lung injury and respiratory failure in ARDS, acute pancreatitis, shock auxiliary and improving prognosis of operation. Ulinastatin, originated from human body, occupying non-immunogenicity and high-security, has greatly clinical value. It is mainly utilized in treatment of acute and chronic relapsing pancreatitis, vulnerarious shock, acute circulatory failure aroused by severe infection. Whether it has the roles in preventing and curing myocardial damage or not has not arrived at the last word. In this study, Preventive and therapeutic effects of ulinastatin on shock heart and its mechanisms were investigated. Material and Method 1. Animal experiment 72 healthy S-D rats, weighting (230±20)g, were randomly divided into two groups: burn group (B group, n=36), ulinastatin-treated group (U group, n=36). Each group divided into pre-burn and post-burn 1, 3, 6, 12, 24 hour subgroups. Animals were inflicted with burn of 30% TBSA. Isotonic saline solution was injected into abdominal cavity according to Parkland formula (4.0ml/kg/1%TBSA). Group U was given ulinastatin (40,000U/kg) intraperitoneally. Blood samples were collected from abdominal aorta at different phase time for the index determination. Myocardial tissues were collected for the indexes determination and pathologic myocardial observation. Blood plasm cTnI, PMN Elastase, TNF-a and IL-10 were determined by ELISA, CK-MB, MDA were assayed by thio-malonylurea chromatometry. Activity of caspase-3 in myocardial tissues was determined by fluorometry, and myocardial cell apoptosis by TUNEL. 2. Clinical research Thirty-four patients, with TBSA>50% , admited into the hospital within 24 hours after burn, and aged 21 to 56 years were enrolled in the study. The patients were divided into control group (B) and ulinastatin-treated group (U), with seventeen patients each. No heart disease history was found and conventional treatment was given to all patients. The patients in U group were given 100,000 U ulinastatin intravenously as soon as admission, three times a day and persisted for a week. Blood samples were withdrawn from vein after 2, 4 and 7 days postburn to determine variables. Result 1. Animal experiment 1) Levels of serum cTnI and CK-MB: Both serum cTnI and CK-MB at 3, 6, 12, 24 hour after burn injury were significantly higher than those before burn (p<0.01). Both serum cTnI and CK-MB in group U were lower than in group B (p<0.01 or p<0.05). 2) TNF-a in myocardial tissues: TNF-a increased after burn injury in two groups (p<0.01), but was lower in group U than that in group B at different phases (p<0.01). 3) IL-10 in myocardium: IL-10 level increased in 1, 3, 6, 12, 24 hour after burn injury in two groups (p<0.01), but were higher in group U than in group B at 3, 6, 12, 24 hour following burns (p<0.01). 4) MDA in myocardial tissues: Level of MDA was elevated significantly at 3, 6, 12 hour after burn injury in group B (p<0.01), but rose only at 12, 24 hour after burn in group U (p<0.01or p<0.05). 5) Activity of caspase-3 in myocardial tissues: The level of caspase-3 increased markedly after burn (p<0.01or p<0.05), especially in group B. 6) IA (index of apoptosis) of myocardial cell: At 3, 6, 12,and 24h following burn,apoptosis of myocardial cells were found in both groups. IA in Group B was significantly higher than that in group U (p<0.01 or p<0.05). 7) Pathomorphological observation: At 3 hour after burn, fiber engorgement, transverse striation derangement, cell boundary unsharpness, cytoplasm destruction, intercellular substance edema were seen. Inflammatory appearances such as blood capillary engorgement, erythrocyte exudation were also observed in myocardial tissues. The pathomorphological changes were aggravated at 6 and 12 hour after burn injury. Dissolvation, degeneration and necrosis were found. The changes in group U were mild than those in group B. 2. Clinical research 1) Level of serum cTnI: Level of serum cTnI at 2, 4, 7 day after burn injury were significantly increased in both groups ( p<0.01) . Serum cTnI in group U at 4, 7 day after burn injury were lower than those in group B (p<0.01 or p<0.05). 2) Level of serum CK-MB: Level of serum CK-MB at 2, 4, 7 day after burn injury were significantly higher than normal level (p<0.01). Its level in group U was lower than that in group B at 2, 4, 7day after burn injury (p<0.01 or p<0.05), and returned to normal level at 7 day after burn injury. 3) Serum PMN Elastase: Level of PMN elastase were higher than normal level in 2, 4, 7 day after burn injury in both groups (p<0.01), but it was lower in group U than that in group B (p<0.01or p<0.05). Discussion and conclusion It was demonstrated that in our animal and clinical studies that severe myocardial damage occurred early following burns. Ulinastatin could alleviate myocardial damage. The mechanisms for the myocardial protection of ulinastatin may be manifold. According to the finding of the present study, suppressing release of pro-inflammatory mediators, reducing release of PMN elastase, alleviating lipid peroxidation and reducing the activity of caspase-3 in myocardium may be the main mechanisms for the effects of ulinastatin on myocardial protection following severe burns.
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