Adult, conscious rats have been exposed to CO-induced hypoxia for 30 min in normoxia, ambient hypoxia (FIO2=14%), or hyperoxia (FIO2=40%). From arterial blood gas analyses, FICO was adjusted in all experimental conditions to obtain final arterial oxygen saturations (SaO2) of ∼60%. Oxygen uptake (V̇O2), ventilation (V̇) and colonic temperature (Tc) were measured in experiments carried out at an ambient temperature of either 25 or 15°C. It was found that CO hypoxia induced marked reductions in the hemoglobin O2 half saturation pressure (P50). Furthermore, isolated reductions in SaO2 (with PaO2 constant) induced decreases in V̇O2 and Tc and increases in ventilation which, as compared with normoxia, were enhanced in ambient hypoxia and reduced but still significant in hyperoxia. As suggested by previous studies, the interactions between SaO2 and PaO2 which operate on the control of metabolism and ventilation originate probably in the central nervous system.
Overall inhomogeneity of ventilation distribution, as measured by single-breath vital capacity (VC) washout (SBW) is known to be greater supine vs. standing. To establish the underlying mechanisms 13 healthy males performed VC SBW of 4% SF(6) and He, standing and supine, with or without a 10 sec breathhold (BH). Overall inhomogeneity, as indicated by normalized phase III slopes, was >50% greater supine (SF(6) 13.1 x 10(-3); He 10.7 x 10(-3) L(-1)) than standing (SF(6) 8.6 x 10(-3); He 6.4 x 10(-3) L(-1); P<0.001). The (SF(6)-He) slope, an index of intraacinar inhomogeneity, did not change with posture. Breathholding, assumed to eliminate convective dependent inhomogeneity within and/or between small lung units, produced twice as great reduction of inhomogeneity when supine vs. standing. After BH inhomogeneity remained significantly greater supine vs. standing. In conclusion, at least two events seem to underlie the increased inhomogeneity when supine: (1) a substantially increased convection dependent non-uniformity between well-separated lung regions; and (2) a somewhat increased convection dependent non-uniformity within and/or between peripherally located lung units.
We have developed a mathematical model of the regulation of ventilation that successfully simulates breathing in the awake as well as in sleeping states. In previous models, which were used to simulate Cheyne-Stokes breathing and respiration during sleep, the controller was only responsive to chemical stimuli, and allowed no ventilation at sub-normal carbon dioxide levels. The current model includes several new features. The chemical controller responds continuously to changes in P(CO(2)) with a lower sensitivity during hypocapnia than in the hypercapnic ranges. Hypoxia interacts multiplicatively with P(CO(2)) over the entire range of activity. The controller in the current model, besides the chemical drive, includes also a neural component. This neural drive increases and decreases as the level of alertness changes, and adds or subtracts from ventilation levels demanded by the chemical controller. The model also includes the effects of post-stimulus potentiation (PSP) and hypoxic ventilatory depression (HVD). While PSP eliminates apneas after a disturbance and also dampens the subsequent dynamics of the respiration, it is not a major factor in the damping of the response. Another finding is that HVD is destabilizing. The model is the first to reproduce results reported in conscious humans after hyperventilation and after acute and longer-term hypoxia. It also reproduces the effects of NREM sleep.
Upper airway (UA) anatomical abnormalities are frequently observed in obstructive sleep apnea syndrome (OSAS). The correspondence between UA anatomical modifications and UA resistance (UAR) had not been studied. We aimed to determine if cephalometric characteristics could be related to segmental UAR. In twenty-five patients (21 males) (15 OSAS patients, 10 snorers) and 10 control subjects (8 males), segmental UAR were measured in supine position and cephalometry was performed. Inspiratory and expiratory UAR were calculated at peak flow. Length of the soft palate (LP), posterior airway space (PAS), distance from hyoid bone to mandibular plane and to posterior pharyngeal wall were different between the groups (P<0.01). Inspiratory and expiratory, total and segmental, UAR were higher in OSAS (P<0.001). Segmental UAR were correlated with PAS and distance from hyoid bone to mandibular plane and to pharyngeal posterior wall (P<0.05). In conclusion, OSAS patients had higher UAR depending on anatomical variables, especially the place of the hyoid bone.
Nitric oxide (NO) has important functions in the regulation of pulmonary smooth muscle tone. In the human lung, published data on the expression and distribution of neuronal nitric oxide synthase (NOS-I) are contradictory. The aim of this study, therefore, was to determine the predominant cells expressing NOS-I in the human lung. Immunofluorescence double staining techniques were applied to normal human lung tissue using established monospecific antibodies directed against NOS-I. Suprisingly, capillary endothelial cells in the alveolar septa were identified as the major sites of NOS-I expression. Neither alveolar nor bronchiolar epithelium, nor the alveolar macrophages, expressed NOS-I. These results indicate that the predominant sites of NOS-I expression in the human lung are confined to non-neuronal, i.e. capillary endothelial cells and suggest a role for NO in the regulation of pulmonary endothelial cell permeability.
