Serum Levels Of Calpain Products As A Novel Biomarker Of Acute Lung Injury Following Cardiopulmonary Bypass

Objective:This study was designed to test the serum calpains levels in patients who undergo cardiac surgery with the technique of cardiopulmonary bypass(CPB),which explore whether the activation of serum calpains can be used as an early biomarker of acute lung injury(ALI)following cardiac surgery,provide new ideas for the treatment and prevention of lung injury after cardiopulmonary bypass.Methods:In this prospective study,patients who underwent cardiac surgery with the technique of cardiopulmonary bypass from February 2022 to July 2022 at the Department of Cardiac and Macrovascular Surgery in the Affiliated Hospital of Yangzhou University were enrolled based on inclusion and exclusion criteria.According to the American-European Consensus Criteria(AECC),these patients were divided into Acute Lung Injury group(ALI)and Non-Acute Lung Injury group(Non-ALI)according to whether acute lung injury occurred after cardiopulmonary bypass surgery.Clinical data and 3ml of blood at the beginning of cardiopulmonary bypass(baseline),1 hour after cardiopulmonary bypass,at the end of cardiopulmonary bypass,1 hour after cardiopulmonary bypass,12 hours after cardiopulmonary bypass,and 24 hours after cardiopulmonary bypass were collected from enrolled patients,and serum calpains activity was measured at each time point using a calpains fluorescence kit.Serum level of calpains in terms of calpains’ activity which was expressed as relative fluorescence unit(RFU)per microliter.SPSS 26.0was used for statistical analysis of all the data,and the results were expressed as 95%confidence intervals,P < 0.05 meant that the difference was statistically significant.Results:In this study,a total of 70 patients met the inclusion criteria,among them,postoperative ALI occurred in 20 cases(28.57%).1.Compared with the non-ALI group,the basic parameters of the cardiac function in basic parameters,operation time,cardiopulmonary bypass time,and clamp time in ALI patients were significantly increased,and perioperative parameters of mechanical ventilation(MV)time,ICU length of stay and total hospital length of stay were significantly extended.2.After the surgery,the level of serum calpains in both groups was significantly increased compared with that before the surgery.At the end of cardiopulmonary bypass,serum calpains levels in the ALI group were initially higher than those in the non-ALI group and were significantly higher than those in the non-ALI group at the time points detected during the subsequent 24 hours.3.After Univariate logistic regression analysis,cardiac function(OR 6.146,95% CI1.608 to 23.484,P = 0.008),operation time(OR 1.048,95% CI 1.024 to 1.071,P <0.001),cardiopulmonary bypass time(OR 1.071,95% CI 1.032 to 1.112,P < 0.001),clamp time(OR 1.040,95% CI 1.010 to 1.070,P = 0.008)and serum calpains levels at 1 h after cardiopulmonary bypass(OR 1.004,95% CI 1.002 to 1.007,P = 0.002)were significantly associated with an increased risk of ALI.After adjusting for multivariate logic analysis,cardiac function(OR 74.171,95%CI 2.067 to 2660.883,P=0.018),operation time(OR 1.084,95%CI 1.024 to 1.147,P=0.005),cardiopulmonary bypass time(OR 1.058,95%CI 1.001 to 1.181,P=0.046)and serum calpains at 1 h after cardiopulmonary bypass(OR 1.011,95%CI 1.00 to 1.021,P=0.033)were highly associated with incidence of postoperative ALI.4.Serum level of calpains at 1 h after cardiopulmonary bypass was correlated with cardiopulmonary bypass time.The diagnostic value of serum level of calpains at 1 h after cardiopulmonary bypass for postoperative ALI was analyzed by ROC curve.The area under the curve was 0.738(95% confidence interval,0.615-0.861).The highest sensitivity and specificity were 33.52(RFU/μl).5.Increased serum level of calpains at 1 h after cardiopulmonary bypass was significantly correlated with the severity of lung injury and poor clinical outcomes,Mechanical Ventilation(MV)time,ICU length of stay and total length of stay.Conclusion:This study showed that cardiac function,operation time,cardiopulmonary bypass time,and clamp time were clinical risk factors for lung injury after cardiopulmonary bypass,and lung injury resulted in significantly longer Mechanical Ventilation duration,ICU stay and total hospital stay.The serum level of calpains was significantly increased after cardiopulmonary bypass,and the increase of serum calpains level was significantly correlated with the occurrence of early postoperative acute lung injury.Serum level of calpains can be used as an early biomarker of lung injury after cardiopulmonary bypass surgery,and has a predictive effect on the occurrence of acute lung injury after cardiopulmonary bypass surgery,and its predictive value has been shown at 1 hour after the surgery.At the same time,elevated serum calpains also predicted a poor clinical outcome.Afterall,an in-depth understanding of the role of calpains in clinical manifestations and development has the potential to better understanding of cardiopulmonary bypass-induced ALI.