Carbon monoxide and hydrogen sulphide reduce reperfusion injury in abdominal compartment syndrome

Background: Carbon monoxide (CO)- and hydrogen sulphide-releasing molecules (CORM-3 and GYY4137, respectively) have been shown to be potent antioxidant and antiinflammatory agents at the tissue and systemic level. We hypothesized that both CORM-3 and GYY4137 would reduce the significant organ dysfunction associated with abdominal compartment syndrome (ACS).

Material and methods: Randomized trial was conducted where ACS was maintained for 2 hours in 27 rats using an abdominal plaster cast and intraperitoneal CO₂ insufflation at 20 mmHg. Three experimental groups underwent ACS and received an experimental molecule at the time of decompression: inactive CORM-3, active CORM-3, and GYY4137, whereas three groups underwent no ACS to serve as a sham. Sinusoidal perfusion, inflammatory response and cell death were quantified in exteriorized livers. Respiratory, liver, and renal dysfunction was assessed biochemically.

Results: Hepatocellular death and the number of activated leukocytes within postsinusoidal venules were significantly increased in rats with ACS (16-fold increase, 17-fold leukocyte activation, respectively, P < 0.05). Administration of CORM-3 or GYY4137 resulted in a significant decrease of both parameters (P = 0.03 and P = 0.009). ACS resulted in an increase in markers of renal and liver injury; CORM-3 or GYY4137 partially restored levels to those seen in sham animals. Myeloperoxidase was significantly elevated in the ACS group in lung, liver, and small intestine (P = 0.0002, P = 0.01, and P = 0.08, respectively). CORM-3 treatment, but not GYY4137, was able to completely block the response (65 ± 11 U/ml and 92 ± 18 U/ml, respectively versus 110 ± 10U/ml in the ACS group, lung tissue).

Conclusions: We have demonstrated the effect of two molecules, CO and hydrogen sulphide, on tempering the reperfusion-associated metabolic and organ derangements in ACS. CORM-3 demonstrated a greater effect than GYY4137 and was able to restore most of the measured parameters to levels comparable to sham.