Protein synthesis inhibition as a potential strategy for metabolic down-regulation.

Summary 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 cv O 2 ) were higher in the PUR group than the controls at 60 min (90 ± 2% versus 80 ± 4%, p 2 ER) decreased from 16.1 ± 1.7% to 6.8 ± 1.2% in the PUR group ( p 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.