title: Dexmedetomidine-ketamine combination mitigates pulmonary type-2 cationic amino acid transporter isozymes upregulation in hemorrhagic shock rats.
abstract: OBJECTIVE
  Dexmedetomidine-ketamine combination has been reported to mitigate inducible nitric oxide synthase (iNOS) upregulation in rats with hemorrhagic shock. Type-2 cationic amino acid transporter isozymes, including CAT-2 and CAT-2B, are essential in regulating iNOS activity. We sought to elucidate the effects of dexme-detomidine-ketamine combination on regulating the expression of pulmonary CAT-2 isozymes in rats with hemorrhagic shock.
  
  
  METHODS
  Forty adult male rats were randomized to one of four groups (10 rats in each group): sham-instrumentation (Sham); sham-instrumentation plus dexmedetomidine-ketamine combination (Sham-D + K); hemorrhagic shock (HS); or hemorrhagic shock plus dexmedetomidine-ketamine combination (HS-D + K). Rats in the HS and HS-D + K groups sustained controlled hemorrhagic shock (mean blood pressure was lowered to 40-45 mmHg by bloodletting for 60 minutes), followed by resuscitation with reinfusion of the shed blood mixed with saline. After close observation for 5 hours, the rats were sacrificed and the expression of CAT-2 isozymes was evaluated.
  
  
  RESULTS
  Sham-instrumentation and dexmedetomidine-ketamine combination did not affect CAT-2 isozymes expression, as pulmonary CAT-2 and CAT-2B mRNA concentrations in the Sham and Sham-D + K groups were low. Hemorrhagic shock significantly upregulated CAT-2 isozymes expression as pulmonary CAT-2 and CAT-2B mRNA concentrations in the HS group were significantly higher than in the two Sham groups. Pulmonary CAT-2 and CAT-2B mRNA concentrations in the HS-D + K group were significantly lower than in the HS group, indicating that the effects of hemorrhagic shock on upregulating CAT-2 isozymes expression were attenuated by dexmedetomidine-ketamine combination.
  
  
  CONCLUSIONS
  Dexmedetomidine-ketamine combination mitigates pulmonary CAT-2 isozymes upregulation in rats with hemorrhagic shock.
authors.affiliation: Department of Anesthesiology, Buddhist Tzu Chi General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Huang
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Tsai
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Huang
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000494:pharmacology; D000778:Anesthetics, Dissociative / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D027202:Cationic Amino Acid Transporter 2 / Q000378:metabolism*; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000494:pharmacology; D004338:Drug Combinations; D007649:Ketamine / Q000008:administration & dosage* / Q000494:pharmacology; D008168:Lung / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018712:Analgesics, Non-Narcotic; D000778:Anesthetics, Dissociative; D027202:Cationic Amino Acid Transporter 2; D004338:Drug Combinations; D020927:Dexmedetomidine; D007649:Ketamine