title: Biologically variable bypass reduces enzymuria after deep hypothermic circulatory arrest.
abstract: BACKGROUND
  Renal injury is common after open-heart surgery. Cardiopulmonary bypass contributes to the problem. We compared conventional nonpulsatile perfusion (NP) to biologically variable perfusion (BVP), which uses a computer controller to restore physiological beat-to-beat variability to roller pump flow. We hypothesized BVP would decrease renal injury after deep hypothermic circulatory arrest.
  
  
  METHODS
  Pigs were randomly assigned to either BVP (n = 9) or NP (n = 9), cooled, arrested at 18 degrees C (1 hour), reperfused, and rewarmed and maintained normothermic (3 hours). Additional pigs had NP for a similar time as above, but without circulatory arrest (n = 3), or were sham-treated without bypass (n = 3). Hemodynamics, acid-base status, temperature, and urine volumes were measured. Urinary enzyme markers of tubular injury were compared post-hoc for gamma glutamyl transpeptidase, alkaline phosphatase, and glutathione S-transferase and by urine proteomics using mass spectrometry.
  
  
  RESULTS
  Urine output at 1 hour after arrest was 250 +/- 129 mL with BVP versus 114 +/- 66 mL with NP (p < 0.02). All three renal enzyme markers were higher with NP after arrest compared with BVP. In animals on bypass without arrest or those sham-treated, no elevations were seen in renal enzymes. Urine proteomics revealed abnormal proteins, persisting longer with NP. Biologically variable perfusion decreased cooling to 21.0 +/- 9.0 minutes versus 31.7 +/- 7.5 minutes (p < 0.002), and decreased rewarming to 22.1 +/- 3.9 minutes versus 31.2 +/- 5.1 minutes (p < 0.002).
  
  
  CONCLUSIONS
  Biologically variable perfusion improved urine output, decreased enzymuria, and attenuated mass spectrometry urine protein signal with more rapid temperature changes. This strategy could potentially shorten bypass duration and may decrease renal tubular injury with deep hypothermic circulatory arrest.
authors.affiliation: Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Rohit K
authors.initials: RK
authors.lastname: Singal
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Docking
authors.forename: Linda G
authors.initials: LG
authors.lastname: Girling
authors.forename: M Ruth
authors.initials: MR
authors.lastname: Graham
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nickerson
authors.forename: Bruce M
authors.initials: BM
authors.lastname: McManus
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Magil
authors.forename: Elizabeth K-Y
authors.initials: EK
authors.lastname: Walker
authors.forename: R Keith
authors.initials: RK
authors.lastname: Warrian
authors.forename: Mary S
authors.initials: MS
authors.lastname: Cheang
authors.forename: W Alan C
authors.initials: WA
authors.lastname: Mutch
mesh_terms: D058186:Acute Kidney Injury / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000469:Alkaline Phosphatase / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects*; D005260:Female; D005982:Glutathione Transferase / Q000652:urine; D013058:Mass Spectrometry; D023421:Models, Animal; D008955:Models, Cardiovascular; D010477:Perfusion / Q000379:methods*; D040901:Proteomics; D011673:Pulsatile Flow / Q000502:physiology*; D013552:Swine; D005723:gamma-Glutamyltransferase / Q000652:urine
chemical_list: D015415:Biomarkers; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D000469:Alkaline Phosphatase