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Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue.

Sonobe T, Chenuel B, Cooper TK, Haouzi P - PLoS ONE (2015)

Bottom Line: The aim of our study was to 1--describe the immediate and long-term neurological effects following H2S-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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, United States of America.

ABSTRACT

Background: Acute hydrogen sulfide (H2S) 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 H2S-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 i.v.) 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 H2S 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.

No MeSH data available.


Related in: MedlinePlus

Immediate outcome in keeping with the number of intra-peritoneal NaHS injections required to produce a coma.There was no difference in the mortality whether 1, 2 or 3 injections were administered. Of note is that the 2 rats that were unable to swim in the H2S groups belonged to the rats that received 3 IP injections.
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pone.0131340.g003: Immediate outcome in keeping with the number of intra-peritoneal NaHS injections required to produce a coma.There was no difference in the mortality whether 1, 2 or 3 injections were administered. Of note is that the 2 rats that were unable to swim in the H2S groups belonged to the rats that received 3 IP injections.

Mentions: Whenever a coma occurred, its characteristics were very stereotypical and similar whether the coma was produced after one, two or three NaHS injections (Fig 3). Typically within one minute following NaHS administration, rats started to present signs of motor agitation, grooming their nose and eyes, along with a tachypnea, while a typical smell of rotten-eggs was detectable. Following this initial phase, all animals rapidly (i.e. within one to 2 minutes) stopped their spontaneous locomotor activity with a phase of muscle hypotonia, starting with the forelimbs. The rats lost their righting reflex and became unresponsive (loss of response to hand clapping or air puffing) around 3 min. Then the animals clearly reduced their breathing frequency leading to irregular ventilation. The latter led to recurrent episodes of apnea and gasping (large and slow breaths). This severe depression in breathing was very often associated with a loss of the corneal reflex. The mechanism of death was a cardiac arrest (disappearance of cardiac pulses) that occurred during this phase of gasping (around 7 minutes after injection). In most rats, gasping was still produced while cardiac pulsations disappear. In the surviving rats, the phase of coma was rather short, lasting on average 3.8 ± 1.0 min (from 2 to 5.6 min). The animals remained unable to use their limbs for a longer period: forelimb hypotonia/paralysis, preventing any efficient grasping or grabbing, lasted 14.6 ± 6.8 min. The animals progressively recovered the mobility of the hindlimbs first, followed by the forelimbs.


Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue.

Sonobe T, Chenuel B, Cooper TK, Haouzi P - PLoS ONE (2015)

Immediate outcome in keeping with the number of intra-peritoneal NaHS injections required to produce a coma.There was no difference in the mortality whether 1, 2 or 3 injections were administered. Of note is that the 2 rats that were unable to swim in the H2S groups belonged to the rats that received 3 IP injections.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482667&req=5

pone.0131340.g003: Immediate outcome in keeping with the number of intra-peritoneal NaHS injections required to produce a coma.There was no difference in the mortality whether 1, 2 or 3 injections were administered. Of note is that the 2 rats that were unable to swim in the H2S groups belonged to the rats that received 3 IP injections.
Mentions: Whenever a coma occurred, its characteristics were very stereotypical and similar whether the coma was produced after one, two or three NaHS injections (Fig 3). Typically within one minute following NaHS administration, rats started to present signs of motor agitation, grooming their nose and eyes, along with a tachypnea, while a typical smell of rotten-eggs was detectable. Following this initial phase, all animals rapidly (i.e. within one to 2 minutes) stopped their spontaneous locomotor activity with a phase of muscle hypotonia, starting with the forelimbs. The rats lost their righting reflex and became unresponsive (loss of response to hand clapping or air puffing) around 3 min. Then the animals clearly reduced their breathing frequency leading to irregular ventilation. The latter led to recurrent episodes of apnea and gasping (large and slow breaths). This severe depression in breathing was very often associated with a loss of the corneal reflex. The mechanism of death was a cardiac arrest (disappearance of cardiac pulses) that occurred during this phase of gasping (around 7 minutes after injection). In most rats, gasping was still produced while cardiac pulsations disappear. In the surviving rats, the phase of coma was rather short, lasting on average 3.8 ± 1.0 min (from 2 to 5.6 min). The animals remained unable to use their limbs for a longer period: forelimb hypotonia/paralysis, preventing any efficient grasping or grabbing, lasted 14.6 ± 6.8 min. The animals progressively recovered the mobility of the hindlimbs first, followed by the forelimbs.

Bottom Line: The aim of our study was to 1--describe the immediate and long-term neurological effects following H2S-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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, United States of America.

ABSTRACT

Background: Acute hydrogen sulfide (H2S) 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 H2S-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 i.v.) 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 H2S 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.

No MeSH data available.


Related in: MedlinePlus