Abstract W P95: Disordered Breathing in a Mouse Model of Ischemic Stoke
| Autor: | Anthony Patrizz, Adam Kolb, Daniel Mulkey, Lousie McCullough |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Stroke. 46 |
| ISSN: | 1524-4628 0039-2499 |
| DOI: | 10.1161/str.46.suppl_1.wp95 |
| Popis: | Background: Stroke induced respiratory dysfunction is a common complication after stroke prolonging recovery and increasing mortality. Animal models are lacking. Central chemoreceptors play a vital role in regulating breathing patterns in response to changes in CO2/H+. The retrotrapezoid nucleus (RTN) in the caudal brainstem contains a population of chemoreceptors that regulate frequency and tidal volume. Activity of these neurons may be regulated by KCNQ channels. We hypothesize that targeting KCNQ channels is a viable option for the treatment of stroke induced breathing disorders. Methods: Whole body plethysmography was performed on WT C57/B6 male mice to establish baseline frequency (BPM), tidal volume (TV), minute volume (MV), periods/durations of apnea and approximate entropy of the system (ApEn). Mice were then subjected to 90 minute MCAO or sham surgery. 72 hours after surgery whole body plethysmography was performed again to identify the stroke disordered breathing phenotype. Mice were randomly assigned to one of two treatment groups: Retigabine (a KCNQ channel activator) or saline at a dose of 50ul/10g SQ, respiratory activity was monitored during a 5 day drug treatment regime. Results: All MCAO-treated mice exhibited disordered breathing characterized by pronounced decrease in respiratory frequency (254.3 ± 15.8 vs.478.2 ± 24.5 BPM) and MCAO-treated mice showed lower ApEn values compared to Sham (0.64 ± .04 vs. 1.02 ± 0.09). There was also a trend for increased number of apneic events in post-stroke animals. No significant differences were observed in TV, suggesting the respiratory phenotype observed in MCAO mice is not due to phenomena. Systemic injection of retigabine suppressed basal respiratory activity of Sham and MCAO-treated animals. Conclusions: Our results suggest that ischemic stroke results in hypoventilation and decreased respiratory stability as evidenced by a decrease in ApEn. Further, considering that retigabine worsened stroke-disordered breathing also suggests that stroke-induced respiratory problems do not result from over activation of the chemoreflex as previously proposed. |
| Databáze: | OpenAIRE |
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