Dexmedetomidine-ketamine Combination Mitigates Pulmonary Type-2 Cationic Amino Acid Transporter Isozymes Upregulation in Hemorrhagic Shock Rats

摘要

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 upregu-lated 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. Conclusion: Dexmedetomidine-ketamine combination mitigates pulmonary CAT-2 isozymes upregulation in rats with hemorrhagic shock.