title: Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass.
abstract: OBJECTIVE
  Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF). This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass.
  
  
  METHODS
  Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6), the control group (Group C, n = 6), and the sham operation group (Group S, n = 6), and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG) from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected.
  
  
  RESULTS
  The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation.
  
  
  CONCLUSIONS
  HLF cardiopulmonary bypass surgery could intensify systemic inflammatory responses and oxidative stress on infant piglets, thus causing acute kidney injury. Ulinastatin might reduce such inflammatory response and oxidative stress and the extent of kidney injury.
authors.affiliation: Department of Anesthesiology, Critical Care and Pain Medicine, the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.|Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiaocou
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Fuxia
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Shoujun
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Shengshou
authors.initials: S
authors.lastname: Hu
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000188:drug therapy / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D006023:Glycoproteins / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000166:cytology / Q000503:physiopathology; D023421:Models, Animal; D018384:Oxidative Stress / Q000502:physiology*; D015427:Reperfusion Injury / Q000473:pathology; D013552:Swine; D018746:Systemic Inflammatory Response Syndrome / Q000473:pathology; D013908:Thoracotomy / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D006023:Glycoproteins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000118:Acetylglucosaminidase; C028665:urinastatin