• Surgery · Sep 2005

    Comparative Study

    Ubiquitin reduces fluid shifts after traumatic brain injury.

    • Steven A Earle, Kenneth G Proctor, Mayur B Patel, and Matthias Majetschak.
    • Division of Trauma and Surgical Critical Care, Ryder Trauma Center, Dewitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
    • Surgery. 2005 Sep 1; 138 (3): 431-8.

    BackgroundUbiquitin has well-described intracellular properties. Recent data also suggest pleiotropic effects of extracellular ubiquitin, including induction of apoptosis, regulation of immune functions, and therapeutic potential during fluid resuscitation from severe trauma. However, the actions of exogenous ubiquitin after traumatic brain injury (TBI) are unknown.MethodsSeries 1: Thirty-five minutes after TBI and hemorrhage, 1.5 mg ubiquitin/kg (n = 5) or albumin (n = 5) intravenous was followed by fluid resuscitation to maintain mean arterial and cerebral perfusion pressure. Series 2: Ubiquitin (n = 5) or vehicle (n = 6) was administered after TBI only. Ubiquitin was measured with enzyme-linked immunosorbent assay in serum, urine (series 1), and cerebrospinal fluid (series 2) for 300 minutes.ResultsSeries 1: After intravenous bolus, serum ubiquitin peaked at t = 45 minutes with a half-life of 54 minutes. Recovery in urine was 10%. With albumin versus ubiquitin, 85% more resuscitation fluid was required to stabilize systemic and cerebral hemodynamics (P < .05 for t = 150 to 300 minutes), but hematocrit was similar. With albumin there were progressive increases in intracranial pressure, peak inspiratory pressure, and decreases in oxygenation. All were significantly attenuated by ubiquitin (all P < .05 vs albumin). Series 2: Intravenous ubiquitin altered cerebrospinal fluid ubiquitin with an increased time to peak (t = 88 +/- 13 min vs 45 +/- 7 min, P < .05) and area under the concentration-time curve (82 +/- 22 vs 23 +/- 11 microg/min(1)/mL(-1), P < .05).ConclusionsAfter TBI, intravenous ubiquitin crossed the blood-brain barrier and significantly reduced third spacing of fluid into the brain and lung during resuscitation.

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