title: Protein synthesis inhibition as a potential strategy for metabolic down-regulation.
abstract: OBJECTIVE
  This pilot study tested the potential of puromycin (PUR) to inhibit protein synthesis and reduce oxygen utilization in a non-hibernating, whole animal preparation.
  
  
  METHODS
  After anesthesia and instrumentation, male rats received a single dose of PUR or 0.9% saline (control), followed 60 min later with [(35)S] methionine/cysteine radiolabeling. Thirty minutes after isotope injection, organ biopsies were taken for quantification of de novo protein synthesis. Arterial and central venous blood gases were obtained at baseline and 60 min after injection of PUR or 0.9% saline. Temperature, mean arterial pressure (MAP), and heart rate were recorded continuously.
  
  
  RESULTS
  Animals receiving PUR demonstrated significant reductions in protein synthesis in all organ systems sampled (p<0.05). The overall reduction averaged 67.8%. Central venous oxygen saturations (S(cv)O(2)) were higher in the PUR group than the controls at 60 min (90+/-2% versus 80+/-4%, p<0.05). The oxygen extraction ratio (O(2)ER) decreased from 16.1+/-1.7% to 6.8+/-1.2% in the PUR group (p<0.05) and increased from 12.5+/-3.2% to 16.0+/-4.2% in the controls (p=0.44). There was no difference in temperature, MAP, heart rate or blood gas variables, other than S(cv)O(2), at baseline or 60 min between groups.
  
  
  CONCLUSIONS
  These results demonstrate that PUR is capable of reducing whole body protein synthesis significantly within a relatively short duration of time. This appears to decrease whole body oxygen utilization as evidenced by an increase in S(cv)O(2) and a decrease in O(2)ER. Protein synthesis inhibition may reduce metabolic demands and should be tested for its potential to improve outcomes where oxygen demands exceed oxygen delivery.
authors.affiliation: Department of Pediatrics, Division of Pediatric Critical Care, VCUHS, P.O. Box 980530, Richmond, VA 23298-0530, USA. mcevans@vcu.edu <mcevans@vcu.edu>
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Evans
authors.forename: Robert F
authors.initials: RF
authors.lastname: Diegelmann
authors.forename: R Wayne
authors.initials: RW
authors.lastname: Barbee
authors.forename: M Hakam
authors.initials: MH
authors.lastname: Tiba
authors.forename: Eric
authors.initials: E
authors.lastname: Edwards
authors.forename: Sue
authors.initials: S
authors.lastname: Sreedhar
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Ward
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D015536:Down-Regulation / Q000187:drug effects*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D011691:Puromycin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000503:physiopathology
chemical_list: D011506:Proteins; D011691:Puromycin