Kenshi Kuno

The nocturnal secretion of cardiac natriuretic peptides during obstructive sleep apnoea and its response to therapy with nasal continuous positive airway pressure

The nocturnal secretion profile of the newly identified natriuretic peptide (NP), brain natriuretic peptide (BNP), was studied in 14 patients with obstructive sleep apnoea syndrome (OSAS) (apnoea hypopnoea index: 60.5±3.4, mean±SE) during two separate nights before and during nasal continuous positive airway pressure (NCPAP) therapy. Plasma levels of NPs (atrial natriuretic peptides; ANP and BNP) were measured at 2‐h intervals during sleep. Simultaneously, blood pressure was measured by a non‐invasive method (Finapres®, Ohmeda, Englewood, CO, USA) and urine was collected for determing volume and catecholamine levels. Urinary and serum sodium concentration were determined before and after the study. Eight non‐snoring subjects were also studied for the investigation of normal nocturnal profiles of BNP levels. To understand the discrete secretion profiles of the two NPs during sleep, blood was sampled from an additional seven patients every 5 min over a 30‐min period around 00.00 and 04.00 hours before NCPAP. In patients with OSAS, plasma BNP levels increased from the beginning of sleep (22:00 h) to the morning (06:00 h) before NCPAP therapy (P< 0.01, anova). Baseline BNP levels were not significantly correlated with patients clinical and poly‐ somnographic parameters. However, in the latter half of the sleep period (02:00–06:00 h), increases in BNP levels during the night before NCPAP therapy were significantly correlated with blood pressure elevations (systolic: r=0.784 P< 0.01, diastolic: r=0.587 P< 0.01) and with apnoea duration (r=0.582 P< 0.01). In normal subjects BP and BNP levels were not changed significantly during sleep. Plasma BNP levels were well correlated with concomitant ANP levels (P< 0.001). NCPAP therapy reduced ANP and BNP levels during sleep and in the morning (P< 0.01). Plasma levels of BNP at 5 min intervals before NCPAP therapy revealed few variations. On the other hand, ANP levels fluctuated over the 30‐min period. Changes in BNP levels during sleep in the patients with OSAS may be related to blood pressure variations, but may be too small to play a significant physiological role in regulating diuresis in OSAS. Further work is required to determine the precise role of dual natriuretic system in cardiovascular load and natriuresis in OSAS.

Age-related changes in the static and dynamic mechanical properties of mouse lungs.

To investigate the effects of aging on pulmonary mechanical properties in mice, we devised a new experimental apparatus to measure the respiratory impedance of excised lungs in mice and examined age-related changes in both static and dynamic properties. In an accelerated senescence-resistant strain of mice, SAMR1 (Takeda, T., Y. Fukuchi, Y. Uejima, K. Teramoto, T. Oka and H. Orino, J. Am. Geriatr. Soc. 39: 911-919, 1991), ranging from 3 to 24 months of age, static compliance (Cst) as well as total lung capacity increased significantly with age, whereas specific compliance and the K value, as determined by exponential analysis, showed no significant change. In the dynamic study, dynamic compliance (Cdyn) increased significantly with age, whereas the frequency dependence of Cdyn (Cdyn/Cst) did not vary with age. From these results we concluded that lung elasticity, normalized to lung volume, remained constant with age and that the effects of aging on pulmonary mechanics might be solely derived from increases in lung volume in the SAMR1 strain of mice.

N-Isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung

N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (Kd) values of 53 ± 2 and 4687 ± 124 nM and maximum binding capacity (Bmax) values of 7 ± 1 and 133 ± 27 pmol/mg protein (n=5) respectively. The IC50 values of various amines were as follows: IMP, 9 × 10−5M; propranolol, 5 × 10−4M; haloperidol, 6 × 10−4M; ketamine, 9 × 10−3M; dopamine, 1 × 10−2M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with Kd values of 54 ± 2 and 5277 ± 652 nM and Bmax values of 7±1 and 103 ± 21 pmol/mg protein (n = 3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue.

The effect of the level of ventilatory assist on the level of respiratory drive in decerebrate cats

The present study was undertaken to investigate whether, independent of changes in PaCO2, ventilatory assist influences not only the pattern but also the level of the respiratory drive. The experiments were performed on decerebrate and paralyzed cats ventilated by a phrenic-driven servo respirator at three different FICO2 levels (0, 0.30, 0.05). The level of ventilatory assist was altered within the range where PaCO2 did not exceed 80 Torr. A higher FICO2 accompanied a higher level of ventilatory assist. The relationship between the minute phrenic activity and log10 PaCO2 at a given FICO2 was linear. No significant difference was found in the regression lines at different levels of FICO2. We conclude that ventilatory assist has little effect on the respiratory drive at a constant level of chemical feedback during hypercapnia.

Intellectual Work Using a Video Game Inhibits Post Hyperventilation Hyperpnoea Following Voluntary Hyperventilation While it Stimulates Breathing At Rest

It has been reported that visual and auditory stimuli significantly increase respiratory frequency (f) and ventilation (\( ({\dot V_E}) \) relative to resting levels (8). However, the effects of intellectual work, which would require widespread parallel activation of central nervous system (CNS) in motor, sensory and associated integrative areas of the cortex, on\( {\dot V_E} \) and breathing patterns have not been well documented. Post hyperventilation hyperpnoea (PHH) (9, 10) or ventilatory afterdischarge (2) is the time-dependent continued hyperventilation after the abrupt termination of a ventilatory stimulus. Plum et al. (6) showed that PHH was frequently impaired in patients with brain disorders. These results have led to the hypothesis that intellectual work could have effects on resting ventilation and PHH in man. To test this hypothesis we evaluated\( {\dot V_E} \), breathing patterns and the changes in PaCO2 using inductive plethysmography and transcutaneous PCO2 (PtcCO2) measurements during intellectual work in normal subjects. We also investigated the effects of intellectual work on PHH following voluntary hyperventilation (VHV) for 3 minutes.

Phase differences between chest and mouth flows in patients suffering from pulmonary disease

The phase difference (PD) between mouth flow and chest flow during rest breathing was measured in pulmonary diseased patients using a body box and the results were compared with normal subjects. Whereas the PD increased in patients with chronic pulmonary obstructive disease (COPD) compared to normal subjects, PD was found to be normal in patients with interstitial pulmonary fibrosis (IPF) (Normal: 2.94 +/- 1.25, COPD: 11.32 +/- 4.17*, IPF: 2.62 +/- 1.67 degrees; *P < 0.01). PD correlated well with FEV1.0/VC%, PFR, RV/TLC, VTG and Ra (r: -0.759, -0.672, -0.788, 0.666, 0.606). From an in-depth analysis of the results, we suggest that the factors which increase PD in COPD patients include hyperinflation of the lung, increases in airway resistance and increases in the parallel inhomogeneity of airway resistance accompanied by an unevenness of alveolar pressures. PD was thought to be clinically useful for the evaluation of the pathological stages of COPD because it reflects the overall clinical manifestations in COPD patients.