Correlation Between Muscle Tissue Specific Micro RNA In Plasma And Diaphragmatic Function In Patients Undergoing Mechanical Ventilation

Objective:Toinvestigatetheeffectofmechanicalventilationon diaphragmatic function in patients undergoing cardiothoracic surgery and figure out the relationship between plasma miRNA and diaphragmatic function in mechanical ventilation patients.Methods:1.Muscle specific miRNA screening:we used the Pubmed database to retrieve the relevant literature through key words and subject words,and screening out the potential miRNA.2.Patient inclusion and plasma collection:patients who were admitted to Department of Critical Care Medicine,Zhongda Hospital,School of Medicine,Southeast University from June to December 2017,aged between 18 and 75 years old,underwent elective cardiac surgery whose mechanical control ventilation time would more than 12h but not more than 48h,would transfer to ICU after cardiac surgery,and signed the knowledge agreement.Patients with the following conditions were excluded:severe respiratory depression,high paraplegia,neuromuscular lesions,chronic obstructive pulmonary disease,emphysema,esophageal obstruction,esophagus perforation,severe esophageal variceal bleeding,and upper gastrointestinal surgery that could not place EAdi catheter,thoracic deformity,diaphragmatic hernia,severe heart,liver,kidney and other organ failure,hemodynamics.Instability;pregnancy;end stage of tumor or family member abandoning active treatment.Peripheral blood sample were collected on the 1 day before operation,before the extubation and the third days after operation,respectively.The plasma was preserved after centrifugation.3,Patient baseline charecters:basic data?sex,age,height,weight,basic disease,diagnosis,APACHE II score,SOFA score,etc?;operation condition?operation type,operation duration,etc?;duration of mechanical ventilation?total mechanical ventilation time,mechanical ventilation control time and auxiliary ventilation time?,conditions of transferring to ICU after the operation and before the extubation?ventilator patterns and parameters,respiratory mechanics index,blood gas analysis,heart rate,mean arterial pressure,types and dosage of vasoactive drugs?;inflammatory markers?white blood cells,PCT and CRP?and plasma albumin level were measured.4,bedside ultrasound and NAVA evaluation of diaphragm function:In one day before operation,before extubation and the third day after operation,using bedside ultrasound assessed diaphragm function,including diaphragmatic inspiratory excursion,thickness of diaphragm and thickening fraction.NAVA was used to evaluate the diaphragm function?NVE and NME?before extubation.5,bedside ultrasound assessed the thickness of skeletal muscle of four limbs,including bicipital muscle of arm and musculi quadriceps femoris.6.Plasma miRNA test:fluorescence quantitative PCR was used to detect the circulating threshold?CT?of muscle tissue specific miRNA in plasma.Results:1.Screening of muscle tissue specific miRNA in plasma.There were 7kinds of eligible miRNA:miR-1,miR-27a,miR-29b,miR-133a,miR-181a,miR-206,miR-499.2.General condition of the selected patients:a total of 40 patients who transfer to ICU after cardiac surgery were analyzed,including 20 coronary bypass surgery patients and 17 heart valve replacements.Male patients accounted for 77.5%,average age was 59.1±12.3 years,APACHE II score was13.9±5.2,and SOFA score was 9.3±3.Duration of operation was 5.1±1.4h,total mechanical ventilation time was 26.1±2.3h,while control ventilation time was22.1±2.2h,and auxiliary mechanical ventilation time was 2.9±1.7h.Length of ICU hospital stay was 2.5±2.4d and total length of hospital stay was25.5±16.7d.3.Effect of mechanical ventilation on diaphragm function:bilateral diaphragmatic activity and thickening fraction decreased significantly before extubation and the third days after the operation compared with 1 day before operation?P<0.05?,but there were no difference between before extubation and the third days after the operation,while diaphragm thickening fraction improved on the third days after the operation.The thickness of bilateral diaphragmatic muscle was significantly higher than that of 1 days before operation and third days after operation?P<0.05?,but there was no difference between 1 days before operation and third days after operation?P>0.05?.Before extubation,NVE was 62.2±22.5 ml/Edi and NME was 1.9±0.9cmH20/Edi.4.Effect of mechanical ventilation on thickness of skeletal muscle of extremities:there was no significant change in the thickness of biceps brachii and the thickness of the four head rectus femoris?P>0.05?at 3 time points in the perioperative period.5.Effect of mechanical ventilation on plasma MyomiR:level of plasma miR-1 and miR-206 in patients after cardiac surgery was significantly lower before extubation than 1 days before operation and third days after operation?3.6±3.7 vs.5.4±4.1 vs.6.0±3.8,P=0.037;4.8±2.8 vs.8±4 vs.7.2±4.2,P=0.001?,but there was no obvious change betweem 1 day before operation and third days after operation.The other 5 miRNA levels did not change significantly during the perioperative period?P>0.05?.6.Correlation of MyomiR and diaphragm function:Ratio of miR-206 and diaphragm thickening fraction on before extubation and third days after preoperative have correlation(r_left=0.427,P_left=0.042;r_right=0.640,P_right=0.000).There was no significant correlation between the other 6 MyomiR and diaphragm function indexes?P>0.05?.7.Correlation of MyomiR and mechanical ventilation control time:There was no significant correlation between the control ventilation time and changes of 7 kinds of MyomiR?P>0.05?.8.Changes in inflammation index and albumin level in perioperative patients:compared with 1 days before operation,the plasma inflammation index CRP,PCT and WBC in the selected patients were significantly higher before extubation and third days after operation?P<0.05?,but there was no significant difference between before extubation and the third days after the operation?P>0.05?.The level of plasma albumin was significantly higher in 1day before operation than before extubation and third days after the operation?P<0.05?,but there was no significant difference between before extubation and the third days after the operation?P>0.05?.Conclusion:short time mechanical ventilation can lead to the decrease of diaphragmatic function in patients with cardiac surgery,and the expression level of miR-1 and miR-206 also decreases,but it is still not recovered to the preoperative level on the third day after operation.The decrease of plasma miR-206 level is positively correlated with the decrease of diaphragm function in mechanically ventilated patients.