title: Contrast-enhanced ultrasound identifies reduced overall and regional renal perfusion during global hypoxia in piglets.
abstract: OBJECTIVE
  It is well known from both clinical experience and animal research that renal hypoxia may lead to temporary or permanent renal failure, the severity being dependent largely on the duration and grade of the hypoxia. The medulla is more susceptible to hypoxic injury than the cortex because approximately 90% of the renal blood flow supplies the cortex. Various methods have been applied to evaluate renal perfusion in both experimental and clinical settings, including magnetic resonance imaging, computed tomography, laser Doppler, and contrast-enhanced ultrasound (CEUS).
  
  
  OBJECTIVE
  The aim of this study was to evaluate changes in overall and regional renal perfusion with CEUS in response to global hypoxia.
  
  
  METHODS
  Twelve newborn anesthetized piglets were exposed to general hypoxia with a fraction of inspired oxygen of 8% of 30 minutes duration. Resuscitation was performed with either 100% oxygen (n = 6) or air (21% oxygen) (n = 6) for 30 minutes followed by 7 hours of reoxygenation with air. Before, during, and after hypoxia, the left kidney was examined with CEUS using 0.2 mL IV of SonoVue followed by 2 mL saline flush. Five additional piglets served as controls. The kidney was examined using a 9-MHz linear transducer with low mechanical index (0.21) and pulse inversion contrast program. One region of interest was drawn in the renal cortex and 1 in the medulla to obtain the corresponding time intensity curves (TICs). From these curves, the peak intensity (PI), time to peak (TTP), upslope of the curve, area under the curve, and mean transit time (MTT) were recorded. Also, the renal arteriovenous transit time (AVTT) was registered. The resistance index (RI) was repeatedly measured in the renal artery. Contrast-enhanced ultrasound was repeated at regular intervals until the animals were sacrificed 8 hours after the hypoxic period.
  
  
  RESULTS
  In the group of 12 piglets subjected to hypoxia, RI increased from 0.69 ± 0.08 at baseline to 0.99 ± 0.09 during hypoxia (P < 0.01), indicating severe general renal vasoconstriction. The AVTT increased from 2.6 ± 0.5 seconds at baseline to 6.7 ± 2.8 seconds during hypoxia (P < 0.001). The PI in the cortex decreased from a mean value of 38.6 ± 6.1 dB at baseline to 30.3 ± 9.7 dB during hypoxia (P < 0.05). In the medulla, only a minor, nonsignificant reduction in PI was observed during hypoxia. In the medulla, TTP and MTT increased from 6.4 ± 1.5 and 9.2 ± 1.7 seconds at baseline to 14.6 ± 8.4 seconds (P < 0.01) and 15.2 ± 5.6 seconds (P < 0.01), respectively, during hypoxia. In the cortex, no statistically significant changes in TTP or MTT were observed during hypoxia. A return to near-baseline values was observed for TTP, PI in both the medulla and cortex, as well as for RI and AVTT within 1 to 3 hours after hypoxia, and they remained relatively constant for the duration of the experiment.Less than 1 hour after the hypoxia, PI both in the cortex and the medulla was significantly higher in the group resuscitated with air than in the group resuscitated with 100% oxygen, 36.0 ± 4.3 versus 27.2 ± 2.2 dB (P < 0.05) and 33.3 ± 8.2 versus 21.1 ± 2.0 dB (P < 0.01), respectively.
  
  
  CONCLUSIONS
  Global hypoxia induced changes in overall and regional renal perfusion detectable with CEUS. Cortical and medullary flows were affected differently by hypoxia; a strong increase in medullary TTP and MTT was observed, indicating a reduction in medullary blood flow velocity. In the cortex, a significant reduction in PI was found, probably because of a reduction in cortical blood volume. A faster recovery of both medullary and cortical PI in the group resuscitated with air could indicate that air might be more beneficial for renal perfusion than hyperoxia during resuscitation after renal hypoxia.
authors.affiliation: From the *Department of Radiology and Nuclear Medicine, †The Intervention Centre, ‡Department of Pathology, §Department of Pediatric Research, and ∥Department of Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Brabrand
authors.forename: Charlotte
authors.initials: C
authors.lastname: de Lange
authors.forename: Kyrre E
authors.initials: KE
authors.lastname: Emblem
authors.forename: Finn P
authors.initials: FP
authors.lastname: Reinholt
authors.forename: Ola Didrik
authors.initials: OD
authors.lastname: Saugstad
authors.forename: Eirik Schram
authors.initials: ES
authors.lastname: Stokke
authors.forename: Berit H
authors.initials: BH
authors.lastname: Munkeby
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D003287:Contrast Media; D000860:Hypoxia / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D055420:Perfusion Imaging / Q000379:methods; D010743:Phospholipids; D012039:Regional Blood Flow; D012077:Renal Artery / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D012079:Renal Circulation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013459:Sulfur Hexafluoride; D013552:Swine; D014463:Ultrasonography / Q000379:methods
chemical_list: D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride