Background: Stroke induced respiratory dysfunction (SIRD) is a common complication of stroke. SIRD delays recovery and increases mortality. Despite the high prevalence of SIRD, the magnitude of breathing dysfunction in stroke patients and its impact on functional recovery is unknown. Even less is known regarding age and sex differences in SIRD and respiratory instability due to the lack of an appropriate animal model of SIRD.
Methods: Whole body plethysmography was performed in WT C57/B6 young (2-3 month)/aged (20 month) male and female mice to establish baseline frequency (BPM), tidal volume (TV), minute ventilation (MV-ml/min/g), periods of apnea, duration of apnea and approximate entropy of the system (ApEn). Mice were then subjected to 60 (aged) or 90 (young) minute MCAO, or sham surgery. 72 hours and 21 days after surgery whole body plethysmography was repeated to identify SIRD phenotype across cohorts.
Results: Three days after stroke aged animals of both sexes exhibit hypoventilation and a reduced ventilatory response to CO2 (Air: male sham 2.13±.1 vs. stroke1.26±.13 MV, p=.01, female sham 2.89±.27 vs. stroke 1.73±.21 p=.001). A significant interaction of age and surgery was noted among males F(1,42)=10.69, p<0.005. At day 21, young males show a recovery in MV (Air: 2.96±.24 vs. day 3 1.95±.35) as a combined result of decreased inter-breath interval (134.6±12.7mS vs. day 3 248.8±37.3,p=.05) and a decrease in apneas (26.6±9.3/min vs. day 3 47.8±11.4).
Conclusions: We found that both age and sex affect ventilatory response following stroke. Aged females showed higher pre-stroke MV and dropped to similar levels as males after stroke, suggesting a more severe effect on breathing in aged females. Aged males demonstrated a more pronounced hypoventilation following stroke than their young counterparts, with less robust recovery. Stabilizing respiratory dysfunction may improve post stroke recovery and cognitive outcomes.