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 CO 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.