ABSTRACT
We examined whether gender specific differences exist in defending inspiratory tidal volumes in the face of upper airway obstruction. In normal weight- and aged-matched men (n=9) and women (n=9), we induced upper airway obstruction with inspiratory flow limitation during NREM sleep by exposing individuals to sub-atmospheric nasal pressure. The mean inspiratory airflow was used to define three distinct levels of upper airway obstruction, based on a mean inspiratory airflow of 175-225 ml/s, 125-175 ml/s and 75-125 ml/s. While duty cycle responses were similar between genders, women had a greater response in T(TOT) at all flow limited conditions. (p<0.05). However, the greater response in T(TOT) led to a more pronounced decline in tidal volume in women compared to men (p<0.05), particularly during the mild and moderate upper airway obstruction. Our data demonstrate that the respiratory rate determines the tidal volume during periods of upper airway obstruction and indicate that individuals with a higher respiratory rate are at risk to develop hypoventilation in face of upper airway obstruction. Because women have a more brisk response in the respiratory rate than men, this may explain the difference in the expression of sleep disordered breathing between genders.
ABSTRACT
We hypothesized that upper airway obstruction (UAO) leads to a compensatory increase in the duty cycle [ratio of inspiratory time to respiratory cycle length (Ti/Tt)], which is determined by genetic factors. We examined the compensatory Ti/Tt responses to 1). UAO and hypercapnia among normal individuals and 2). hypercapnia in different inbred strains, C3H/HeJ (C3) and C57BL/6J (B6), and their first- and second-generation (F2) offspring. 3). We then used the compensatory Ti/Tt response in the F2 to determine genetic linkage to the mouse genome. First, normal individuals exhibited a similar increase in the Ti/Tt during periods of hypercapnia (0.11 +/- 0.07) and UAO (0.09 +/- 0.06) compared with unobstructed breathing (P < 0.01). Second, the F2 offspring of C3 and B6 progenitors showed an average Ti/Tt response to 3% CO2 (0.42 +/- 0.005%) that was significantly (P < 0.01) greater than that of the two progenitors. Third, with a peak log of the odds ratio score of 4.4, Ti/Tt responses of F2 offspring are genetically linked to an interval between 58 and 64 centimorgans (cM) on mouse chromosome 5. One gene in the interval, Dagk4 at 57 cM, is polymorphic for C3 and B6 mice. Two other genes, Adrbk2 at 60 cM and Nos1 at 65 cM, have biological plausibility in mechanisms of upper airway patency and chemosensitivity, respectively. In summary, Ti/Tt may serve as an intermediate physiological phenotype for compensatory neuromuscular response mechanisms for maintaining ventilation in the face of UAO and hypoventilation and to help target specific candidate genes that may play a role in the expression of sleep-disordered breathing.
