| Part OneSafety and Therapeutic Effects of Cyclosporine A on Peri-operative Inflammatory Response and Myocardial Injury in Patients Underwent Heart Valve ReplacementOBJECTIVES:To investigate the safety and therapeutic effects of Cyclosporine A (CsA) on perioperative inflammatory response and myocardial injury in patients underwent heart valve replacement.METHODS:Patients with rheumatic heart valve disease admitted in the department of cardiovascular surgery of Xijing Hospital, intended for simultaneous mitral and aortic valves replacement, were enrolled in the study. Eligible patients were randomized into control and CsA treatment groups. CsA(5mg/kg) was administered via cardiopulmonary bypass circuit after heart arrested with cardiolplegia in CsA group, while no special treatment was used in control group. Patients'serum samples were collected just before the operation as well as 3h, 6h, 12h, 24h and 48h after arriving at ICU. Serum concentration of high mobility group box 1 (HMGB1) protein, cardiac troponin I (cTnI), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) were detected with Enzyme-linked Immunosorbent Assay(ELISA) methods by physician who unaware of the patients'allocation. Clinical parameters such as inotropic drug use after arriving at ICU, post operative mechanical ventilation time, volume of drainage and transfusion, survival or death, hours of ICU stay and days of postoperative hospitalization were also recorded.RESULTS:(1) Serum HMGB1 concentrations in both groups elevated immediately after operation, and reached peak at 24 and 3 post-operative hours in control and CsA group respectively. The serum concentrations of HMGB1 at 24 and 48 post-operative hour in CsA group significantly decreased compared with those of control group respectively (p<0.05). (2) Serum concentrations of cTnI increased after operation in both groups. The serum concentrations of cTnI at 6, 12 and 24 post-operative hour in CsA group significantly decreased compared with those of control group respectively (p<0.05). (3) The serum concentrations of IL-6 increased to peak at 3h after arriving at ICU in both groups. There were no statistical differences between the two groups at all time points except at 3h after operation, at which the concentration of IL-6 in CsA group significantly decreased compared with that in control group (p=0.04). (4) The serum concentrations of IL-8 in both groups are increased to peak 3h after the operation. There were no significant differences between the two groups at all time points observed (p>0.05). (5) The serum concentrations of TNF-αin both groups reached peak at 3h after operation. There were no statistical differences between the two groups at all time points observed (p>0.05). (6) The clinical parameters after operation had no significant differences between the two groups as to inotropic drug use after arriving at ICU, post operative mechanical ventilation time, volume of drainage and transfusion, survival or death, hours of ICU stay and days of postoperative hospitalization.CONCLUSION:CsA can efficiently decrease the post-operative inflammatory responses and myocardial injury in patients underwent heart valve replacement operation, but has no significant impact on the clinical results in this small size clinical trial.Part two Therapeutic Effects of Adenosine Pretreatment on Peri-operative Inflammatory Response and Myocardial Injury in Patients Underwent Heart Valve ReplacementOBJECTIVES:To investigate the therapeutic effects of adenosine pretreatment on peri-operative inflammatory response and myocardial injury in patients underwent heart valve replacement.METHODS:Patients with rheumatic heart valve disease admitted in the department of cardiovascular surgery of Xijing Hospital, intended for simultaneous mitral and aortic valves replacement, were enrolled in the study. Eligible patients were randomized into control and adenosine pretreatment groups. Adenosine (150μg/kg/min) was administered via jugular vein cannulation for 10 min before start of cardiopulmonary bypass in the adenosine group, while no special treatment was used in control group. Patients'serum samples were collected just before the operation as well as 3h, 6h, 12h, 24h and 48h after arriving at ICU. Serum concentration of high mobility group box 1 (HMGB1) protein, cardiac troponin I (cTnI), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) were detected with Enzyme-linked Immunosorbent Assay (ELISA) methods by physician who unaware of the patients'allocation. Clinical parameters such as inotropic drug use after arriving at ICU, post operative mechanical ventilation time, volume of drainage and transfusion, survival or death, hours of ICU stay and days of postoperative hospitalization were also recorded.RESULTS:(1) Serum HMGB1 concentrations in both groups elevated immediately after operation, and there were no statistic differences beteen the two groups at all time points (p>0.05). (2) Serum concentrations of cTnI increased after operation in both groups. The serum concentrations of cTnI at 6 post-operative hour in adenosine group significantly decreased compared with that of control group (p<0.05). (3) Serum IL-6 concentrations in both groups elevated immediately after operation, and then decreased slowly, there were no statistic differences between the two groups (p>0.05). (4)Concentrations of IL-8 in both groups elevated to peak right after operation. The serum concentrations of IL-8 at 6 post-operative hour in adenosine group significantly decreased compared with that of control group (p<0.05). (5) Concentrations of TNF-αin both groups elevated to peak at 3 hours after operation. There were no statistical differences between the two groups at all time points observed (p>0.05). (6)As to the clinical parameters after operation, the transfusion volume of adenosine group was significantly less than that of control group (2333±1919ml vs 3177±3662ml, p=0.041), the time of ICU stay of adenosine group was significantly shorter than that of control group (66.0±33.4h vs 86.8±76.3h, p=0.034). There was no significant impact on the other clinical results in this small size clinical trial.CONCLUSION:Adenosine can decrease the post-operative inflammatory responses and myocardial injury in patients underwent heart valve replacement operation,and also related to better clinical results. |
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