Journal of applied physiology
-
A recent study by our laboratory has shown that an increase in intrathoracic temperature activates vagal pulmonary C-fibers. Because these afferents are known to elicit reflex bronchoconstriction upon stimulation, this study was carried out to investigate if an increase in airway temperature within the physiological range alters bronchomotor tone. Adult guinea pigs were anesthetized and mechanically ventilated via a tracheal tube. ⋯ These results indicate that the increase in airway temperature induced transient airway constriction in guinea pigs. Approximately two-thirds of the increase in bronchomotor tone was mediated through the cholinergic reflex, which was probably elicited by the activation of TRPV1-expressing airway afferents. The remaining bronchoconstriction was caused by other, yet unidentified factors.
-
Autoresuscitation is a critical survival-promoting mechanism in mammals that allows recovery from primary apnea via hypoxia-induced gasping. Here we show, using head-out plethysmography, that gasping behavior is altered during autoresuscitation, and the autoresuscitation response is delayed, in neonatal 5-hydroxytryptamine (5-HT) neuron-deficient Pet-1 homozygous (Pet-1(-/-)) mice. When exposed to 97% N(2)-3% CO(2) on postnatal day 4.5, unanesthetized Pet-1(-/-) mice required over four times longer than age-matched wild-type controls to initiate gasping following primary apnea. ⋯ However, when the exposure to anoxia was unrelenting, gasping frequency, the form of the gasps, the total number of gasps produced, the duration of the gasping period, and time to last gasp were comparable to controls. Plethysmographic testing of the same mutants on postnatal day 9.5 revealed that their autoresuscitation responses, although improved compared with day 4.5, remained significantly longer than in wild-type controls. Our data indicate that despite a severe deficiency of central 5-HT neurons, Pet-1(-/-) neonatal mice are capable of gasping, but their gasping pattern is altered during autoresuscitation, leading to a prolongation of the time required to recover from hypoxia-induced apnea.
-
The factors regulating lung aeration and the initiation of pulmonary gas exchange at birth are largely unknown, particularly in infants born very preterm. As hydrostatic pressure gradients may play a role, we have examined the effect of a positive end-expiratory pressure (PEEP) on the spatial and temporal pattern of lung aeration in preterm rabbit pups mechanically ventilated from birth using simultaneous phase-contrast X-ray imaging and plethysmography. Preterm rabbit pups were delivered by caesarean section at 28 days of gestational age, anesthetized, intubated, and placed within a water-filled plethysmograph (head out). ⋯ In contrast, ventilation with 5-cmH(2)O PEEP gradually increased aeration of the distal airways, which did not collapse at end expiration. The FRC achieved in pups ventilated with PEEP (19.9 +/- 3.2 ml/kg) was significantly greater than in pups ventilated without PEEP (-2.3 +/- 3.5 ml/kg). PEEP greatly facilitates aeration of the distal airways and the accumulation of FRC and prevents distal airway collapse at end expiration in very preterm rabbit pups mechanically ventilated from birth.
-
We hypothesized that some of the heterogeneity of pulmonary blood flow present in the normal human lung in normoxia is due to hypoxic pulmonary vasoconstriction (HPV). If so, mild hyperoxia would decrease the heterogeneity of pulmonary perfusion, whereas it would be increased by mild hypoxia. To test this, six healthy nonsmoking subjects underwent magnetic resonance imaging (MRI) during 20 min of breathing different oxygen concentrations through a face mask [normoxia, inspired O(2) fraction (Fi(O(2))) = 0.21; hypoxia, Fi(O(2)) = 0.125; hyperoxia, Fi(O(2)) = 0.30] in balanced order. ⋯ Neither mean proton density [hypoxia, 0.46(0.18) g water/cm(3); normoxia, 0.47(0.18) g water/cm(3); hyperoxia, 0.48(0.17) g water/cm(3); P = 0.28] nor mean density-normalized perfusion [hypoxia, 4.89(2.13) ml x min(-1) x g(-1); normoxia, 4.94(1.88) ml x min(-1) x g(-1); hyperoxia, 5.32(1.83) ml x min(-1) x g(-1); P = 0.72] were significantly different between conditions in either imaging plane. Similarly, perfusion heterogeneity as measured by relative dispersion [hypoxia, 0.74(0.16); normoxia, 0.74(0.10); hyperoxia, 0.76(0.18); P = 0.97], fractal dimension [hypoxia, 1.21(0.04); normoxia, 1.19(0.03); hyperoxia, 1.20(0.04); P = 0.07], log normal shape parameter [hypoxia, 0.62(0.11); normoxia, 0.72(0.11); hyperoxia, 0.70(0.13); P = 0.07], and geometric standard deviation [hypoxia, 1.88(0.20); normoxia, 2.07(0.24); hyperoxia, 2.02(0.28); P = 0.11] was also not different. We conclude that HPV does not affect pulmonary perfusion heterogeneity in normoxia in the normal supine human lung.
-
Opioid drugs disrupt signaling in the brain stem respiratory network affecting respiratory rhythm. We evaluated the influence of a steady-state infusion of a model opioid, remifentanil, on respiratory variability during spontaneous respiration in a group of 11 healthy human volunteers. We used dynamic linear and nonlinear models to examine the effects of remifentanil on both directions of the ventilatory loop, i.e., on the influence of natural variations in end-tidal carbon dioxide (Pet(CO(2))) on ventilatory variability, which was assessed by tidal volume (Vt) and breath-to-breath ventilation (i.e., the ratio of tidal volume over total breath time Vt/Ttot), and vice versa. ⋯ The obtained models revealed a decrease in the strength of the dynamic effect of Pet(CO(2)) variability on Vt (the "controller" part of the ventilatory loop) and a more pronounced increase in the effect of Vt variability on Pet(CO(2)) (the "plant" part of the loop). Nonlinear models explained these dynamic interrelationships better than linear models. Our approach allows detailed investigation of drug effects in the resting state at the systems level using noninvasive and minimally perturbing experimental protocols, which can closely represent real-life clinical situations.