Interaction of hypoxia and hypercapnia on ventilation, tidal volume and respiratory frequency in the anaesthetized rat

1. Ventilation ( V(E)), tidal volume (V(T)), respiratory frequency (f) and arterial and end-tidal gas tensions were measured in seventy-one tracheostomized New Zealand white rats ( approximately 405 g) anaesthetized with an initial dose of pentobarbitone followed by repeated small doses to ensure that a weak limb-withdrawal reflex remained.2. O(2) consumption (1.2 ml (s.t.p.d.) min(-1) 100 g(-1)), CO(2) production (1.0 ml (s.t.p.d.) min(-1) 100 g(-1)), heart rate (357 min(-1)), V(E) (43 ml min(-1) 100 g(-1)), P(a,CO2) (34 mmHg) and P(a,O2) (84 mmHg) in the control periods did not change significantly during the course of the experiment.3. Inspirates of 21% O(2) with 2-10% CO(2), 15, 10 or 7.5% O(2) with either no or sufficient CO(2) to maintain normocapnia and 15 or 10% O(2) with 4, 6 or 8% CO(2) were tested. Steady-state responses were measured after 2 min of exposure.4. Hypoxic-hypercapnic interaction on V(E), V(T) and f determined by a three-inspirate test ((i) hypoxia alone, (ii) hypercapnia and (iii) these hypoxic and hypercapnic levels combined) yielded various conclusions depending on the level of asphyxia examined. Essentially, the milder the asphyxia the more the interaction appeared additive or even multiplicative and the stronger the asphyxia the more the interaction appeared occlusive. However, this test is unsuitable for accurately showing interactions because the P(a,O2) achieved in asphyxia was higher than in hypoxia and the asphyxial P(a,CO2) was lower than in hypercapnia.5. For isoxic conditions (P(a,O2) = 97, 77 and 51 mmHg), V(E) and V(T) were related linearly to P(a,CO2) whilst f was related hyperbolically with convexity upwards (P(a,O2) 97 mmHg) or downwards (P(a,O2) 77 and 51 mmHg).6. For isocapnic conditions (P(a,CO2) = 33, 40 and 48 mmHg), V(E) and V(T) were inversely related to P(a,O2) with a hyperbolic curve (convexity downwards) whilst f was inversely and linearly related (P(a,CO2) 33 mmHg) or constant (P(a,CO2) 40 and 48 mmHg).7. Multivariate analyses showed that the hypoxic-hypercapnic interaction was additive for V(T) but occlusive for V(E) and f and the occlusion was more severe in the latter. This was illustrated graphically for the variable plotted against P(a,CO2) or P(a,O2) as parallel shifts in regression lines for V(T), flatter regression lines for V(E) during asphyxia and a virtually constant f during asphyxia.8. V(E) responses and sensitivities to hypoxia and hypercapnia, the shape of V(E), V(T) and f regression lines against P(a,O2) and P(a,CO2) and the type of hypoxic-hypercapnic interaction on each variable in the rat were compared with other species.9. Possible causes of the occlusive hypoxic-hypercapnic interaction in the rat were considered.