Immediate and Long-Term Outcome of Acute H(2)S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue

BACKGROUND: Acute hydrogen sulfide (H(2)S) poisoning produces a coma, the outcome of which ranges from full recovery to severe neurological deficits. The aim of our study was to 1- describe the immediate and long-term neurological effects following H(2)S-induced coma in un-anesthetized rats, and 2- determine the potential benefit of methylene blue (MB), a compound we previously found to counteract acute sulfide cardiac toxicity. METHODS: NaHS was administered IP in un-sedated rats to produce a coma (n = 34). One minute into coma, the rats received MB (4 mg/kg IV) or saline. The surviving rats were followed clinically and assigned to Morris water maze (MWM) and open field testing then sacrificed at day 7. RESULTS: Sixty percent of the non-treated comatose rats died by pulseless electrical activity. Nine percent recovered with neurological deficits requiring euthanasia, their brain examination revealed major neuronal necrosis of the superficial and middle layers of the cerebral cortex and the posterior thalamus, with variable necrosis of the caudate putamen, but no lesions of the hippocampus or the cerebellum, in contrast to the typical distribution of post-ischemic lesions. The remaining animals displayed, on average, a significantly less effective search strategy than the control rats (n = 21) during MWM testing. Meanwhile, 75% of rats that received MB survived and could perform the MWM test (P<0.05 vs non-treated animals). The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals. However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB. CONCLUSION: In conclusion, in rats surviving H(2)S induced coma, spatial search patterns were used less frequently than in control animals. A small percentage of rats presented necrotic neuronal lesions, which distribution differed from post-ischemic lesions. MB dramatically improved the immediate survival and spatial search strategy in the surviving rats.