title: Methylprednisolone increases urinary nitrate concentrations and reduces subclinical renal injury during infrarenal aortic ischemia reperfusion.
abstract: OBJECTIVE
  This study tests the hypothesis that methylprednisolone may influence eNOS activity in renal arterial and venous vascular beds and impede subclinical renal injury.
  
  
  BACKGROUND
  Acute renal failure is a major complication of cardiovascular surgery. Renal damage arises in part from excessive vasoconstriction mediated by an imbalance of vasoconstrictive ET-1 and vasodilatory NO produced by eNOS. While methylprednisolone may reduce subclinical renal injury as measured by urinary N-acetyl-beta-D-glucosaminidase (beta-NAG), its effects upon eNOS activity in renal arterial and venous vascular beds, reflected by urinary nitrate levels, is unclear.
  
  
  METHODS
  A porcine model of normotensive, euvolemic infrarenal aortic ischaemia-reperfusion was used. Forty-two pigs underwent a 60-minute laparotomy followed by 150 minutes of infrarenal ischemia and 180 minutes of reperfusion. Animals were randomized to receive methylprednisolone 30 mg/kg or placebo after induction of general anesthesia. Urinary beta-NAG levels were assessed as an index of subclinical renal injury, whereas urinary nitrate was assessed as an indicator of eNOS activity in renal arterial and venous vascular beds.
  
  
  RESULTS
  Methylprednisolone treatment did not influence mean arterial, central venous, or pulmonary artery wedge pressures but suppressed plasma IL-6 levels. After the ischemia-induced rise from preanaesthetic baseline levels, urinary beta-NAG levels declined to significantly lower values in the MP group, indicative of MP renal protection (P < 0.05). Conversely, urinary nitrate levels indicative of vascular e-NOS activity remained significantly and persistently higher in MP-treated animals (P < 0.05).
  
  
  CONCLUSIONS
  This study, in a porcine model of renal ischaemia-reperfusion injury, shows the benefits of methylprednisolone pretreatment in enhancing urinary nitrate levels indicative of vascular eNOS activity and the reduction of urinary beta-NAG levels, which represent subclinical renal injury.
authors.affiliation: Queen's University of Belfast, Belfast, Northern Ireland. robincbaker@hotmail.com
authors.forename: Robert C
authors.initials: RC
authors.lastname: Baker
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Armstrong
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McClean
authors.forename: Declan
authors.initials: D
authors.lastname: O'Rourke
authors.forename: Frederick C
authors.initials: FC
authors.lastname: Campbell
authors.forename: Aires A B Barros
authors.initials: AA
authors.lastname: D'Sa
authors.forename: William T
authors.initials: WT
authors.lastname: McBride
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control / Q000652:urine; D000818:Animals; D001012:Aorta, Abdominal; D015415:Biomarkers / Q000652:urine; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply*; D008775:Methylprednisolone / Q000627:therapeutic use*; D009566:Nitrates / Q000652:urine*; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000652:urine*; D012720:Severity of Illness Index; D013053:Spectrophotometry; D013552:Swine; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D009566:Nitrates; D000118:Acetylglucosaminidase; D008775:Methylprednisolone