The physiological significance of the chemical regulation of respiration for blood gas homeostasis is reviewed. In particular, its role in the state of impaired gas exchange is considered.
For the quantitative evaluation of the ventilatory activities of the driving system, ΔV₅₀ and D were examined by the withdrawal test and by the CO₂ response curve during hyperoxia for peripheral and central chemoreceptor activities, When ΔV₅₀ and D plotted against PaCO₂ and PaO₂ were observed at rest in 37 patients with pulmonary disease, these indices were significantly decreased in patients with PaO₂ lower than 70mmHg and PaCO₂ higher than 50mmHg. Depression of ventilatory response to chemical drives was more pronounced in the patients with higher PaCO₂ than low PaO₂.
Steady state response to hypoxia was found to be higher than ΔV₅₀. This may be attributed to the fact that hypoxic drive via the peripheral chemoreceptors is integrated, modified or even depressed in the brain stem respiratory centers. Evidence of medullary depression during hypoxia was present in a patient with bilateral carotid chemoreceptor resection over 20 years previously.
Electro-physiological studies on the ventral surface of the medulla oblongata where the central chemosensitive areas are supposed to be located are presented. Cells with specifically H⁺ dependent membrane potential were detected. We at present suspect that this potential varies in accordance with extracellular K⁺ concentration which is released by chemoreceptive cell excitation. Unsolved problems related to central chemosensitivity mechanisms are discussed.

View full abstract

To investigate the buffer mechanism of cerebrospinal fluid in acute hypercapnia in vivo, we have studied the acid-base status of CSF in 14 mongrel dogs, changing their inspiratory CO₂ concentration, from room air to 6% and then to 12%. Each condition was maintained for two hours, and at the end of each CO₂ loading, arterial and CSF samples were taken anaerobically for the determination of PO₂, PCO₂, pH and [HCO₃^-] by electrode and Van Slyke-gas chromatograph system. Buffer values, Δ[HCO₃^-]/ΔpH were calculated for blood and CSF between room air and 6% CO₂ breathing and also between 6% and 12% CO₂ breathing.
As results, followings were concluded:
1) The buffer values of CSF in vivo in acute hypercapnia were significantly higher than those of arterial blood.
2) The buffer values of CSF increased significantly with increases of CSF PCO₂.
3) An active transport system is presumably necessary for the explanation of this PCO₂ dependent buffer mechanism, in which the participation of carbonic anhydrase would be suggested.

View full abstract

Asthma is a clinical syndrome manifested by reversible and intermittent obstruction of the bronchi. The reported incidence of aspirin-induced asthma varies from 2.3 to 20.0%, and causes the highest incidence of all drug-induced asthma. Nevertheless the etiology of aspirin-induced asthma is unknown.
The present investigation was conducted to explore the effects of aspirin on the contraction of guinea-pig tracheal tissues with various bronchoconstrictors. Male guinea-pigs, weighing 250-300g, were killed. Guinea-pig tracheal tissues were removed and suspended in a bioassay glass jackets and superfused with Krebs-Hensleit solution at 37°C, saturated with oxygen and carbon dioxide (95:5, v/v). Contraction of tissues was detected by an isotonic transducer and displayed on a polyrecorder.
1) The contractile responses of guinea-pig tracheal tissues with acetylcholine were markedly increased with continuous infusion of aspirin and were dose related.
2) The contractile responses of guinea-pig tracheal tissues with histamine, serotonin, prostaglandin F_2α and bradykinin were increased with continuous infusion of aspirin and became bigger by increasing the dose of aspirin.
3) These results suggest that aspirin lowers the threshold of various bronchoconstrictors, and that such a mechanism may play a very important role in the pathophysiological aspects of aspirin-induced asthma.

View full abstract

The recognized biological role of cyclic AMP has grown from a relatively simple role in liver glycogenolysis to the point where it appears to be a key regulatory agent in most mammalian tissues.
The present investigation was conducted to explore the effect of various vasoactive substances on the cyclic nucoleotide contents of guinea-pig lung and tracheal tissues.
Male guinea-pigs, weighing 250-300g, were used. The cyclic nucleotide contents of guinea-pig lung and tracheal tissues were determined by radioimmunoassay method.
1) The cyclic nucleotide contents of guinea-pig lung and tracheal tissues reached a maximum in about 15min. by incubating with aminophylline (1mM), decreased and reached a plateau in about 30min..
2) The cyclic AMP content of guinea-pig tracheal tissues reached a maximum in 2min. by incubating with acetylcholine, isoproterenol, prostaglandin E₂ (PGE₂) and histamine, reached a maximum in 3min. by incubating with PGF_2α.
3) The cyclic AMP content of guinea-pig lung tissues reached a maximum in 2min. by incubating with isoproterenol, PGE₂ and histamine, reached a maximum in 3min. by incubating with PGF_2α.
4) The cyclic GMP content of guinea-pig tracheal tissues reached a maximum in 2min. by incubating with acetylcholine and histamine, and did not show any change by incubating with isoproterenol and PGE₂.
5) The cyclic GMP contents of guinea-pig lung tissues reached a maximum in 2min. by incubating with PGF_2α and histamine, reached a maximum in 1min. by incubating with acetylcholine and PGE₂, and did not show any change by incubating with isoproterenol.

View full abstract

There is the hypothesis that stimulation of β sites leads to an increase in adenylate cyclase activity, an increase in intracellular cyclic AMP concentration and a corresponding change in cell function, and that stimulation of α sites decreases adenylate cyclase activity, diminishes cyclic AMP concentration and leads to the opposite change in cell function.
The present investigation was conducted to explore the effect of various vasoactive substances on the cyclic nucleotide contents of guineapig lung and tracheal tissues.
Male guinea-pigs, weighing 250-300g, were used. The cyclic nucleotide contents of guinea-pig lung and tracheal tissues were determined by radioimmunoassay method.
1) The cyclic AMP and cyclic GMP contents of guinea-pig lung and tracheal tissues increased dose dependently by incubating with histamine, serotonin, bradykinin and acetylcholine.
2) The cyclic AMP contents of guinea-pig tracheal tissues increased dose dependently by incubating with isoproterenol, while the cyclic GMP content did not show any change.
3) The cyclic GMP content of guinea-pig tracheal tissues increased markedly by incubating with angiotensin II (AII), while the cyclic AMP content showed moderate increase. The cyclic AMP content of guinea-pig lung tissues increased slightly by incubating with AII, while the cyclic GMP content did not show significant change.
4) The cyclic AMP content of guinea-pig lung and tracheal tissues increased dose dependently by incubating with VIP, while the cyclic GMP content of guinea-pig tracheal tissues increased slightly, and that of guinea-pig lung tissues decreased at a dose of 5 μg/ml.

View full abstract

This study was carried out to evaluate whether or not alveolar lining materials influence the levels of lysosomal enzymes in mononuclear phagocytes. Pulmonary washings (PW) obtained from normal rabbit lungs were used as a sample of alveolar lining materials. When PW was added to the monolayers of mononuclear phagocytes including alveolar macrophages, peritoneal exudate cells, peritoneal cells and blood monocytes in rabbits, the levels of lysosomal enzyme β-galactosidase in these cells were elevated 24 hours after incubation. The enzyme-inducing factor in PW was found to be filterable, nondialysable and heat-labile, and the activity was dose-dependent and pH-dependent. No pyrogenic effect was found. Gel-filtration of PW through Sepharose 4B yielded five fractions. The factor was in the third fraction (m. w. 200, 000 to 700, 000), and the minimum responses were obtained by the third fraction at a protein concentration of 25μg/ml. The activity was decreased by trypsin treatment.
These results may suggest that increased levels of lysosomal enzymes in normal alveolar macrophages are induced by endogenous factors such as enzyme-inducing factors in the lining materials of normal alveolar spaces rather than by inhaled exogenous stimulants.

View full abstract

The significance of phase IV of the N₂ method is not understood sufficiently to be used as a routine clinical test. We analyzed closing volume tracings by the N₂ method in twenty five asymptomatic patients with bronchial asthma and fourteen healthy non-smokers as a control group. Two methods were applied to all subjects, namely, the original N₂ method and a modified N₂ method in which preinspiratory lung volume was kept at RV+600ml by adding dead space. The results were summarized as follows:
1) By the original N₂ method only four out of twenty five patients with bronchial asthma showed abnormal closing vloumes and eight patients had increased phase III slope (ΔN₂). Eleven patients were abnormal in either parameter. Closing volume tracings demonstrated a relatively flat phase IV in the patients making the inflection point between phases III and IV unclear.
2) The modified N₂ method brought consistently higher closing volumes, ΔN₂, and amplitude of cardiac oscillation than the original method in the control group. However, in patients with asymptomatic asthma, changes of ΔN₂ and cadiac oscillation by adding dead space did not show any consistent trend. In several patients phase IV change was characteristic in that it appeared at much higher lung volumes, leading to a detection of another six patients with abnormal closing volumes. Four out of these six patients had increased ΔN₂ by the original method, implying that these abnormal phase III slopes might be due to poorly identified phase IV.
We concluded that the modified N₂ method was superior to the original method for the detection of anormal phase IV but that the latter was still useful if phase III and IV were analysed together.

View full abstract

The purpose of this study was to evaluate the role of the diastolic pressure-volume relationship of the right ventricle. Twenty-four patients consisting of 4 with normal hemodynamics, 11 with heart diseases and 9 with pulmonary diseases were studied. Ages ranged from 17 to 76 years. Right heart catheterization was performed in all cases and the right ventricular residual ratio (RVRR) was measured by the RI method.
Patients with heart and pulmonary diseases had nearly the same degree of mild to moderate pulmonary hypertension at the time of this study. Passilve elastic modulus (k) was calculated from right ventricular endo-diastolic volume and pressure by the formula P=be^kV (Gaasch). dV/dP (cc/m²/mmHg)=e^-kV/kb or 1/kP and dV/Vdp (mmHg^-1) =dV/dP 1/V were also calculated.
Passive elastic modulus of cases with normal hemodynamics was 0.023±0.003, heart diseases 0.018±0.002 and pulmonary diseases 0.014±0.002. The k value was significantly different between normal hemodynamics and pulmonary diseases (p<0.01). The values of dV/dP and dV/VdP in cases with pulmonary diseases tend to be high. value Correlation between k and paO₂ (r=0.440, p<0.05), k and stroke index (r=-0.451, p<0.05), and k and right ventricular work index (r=-0.670, p<0.01) respectively were significant. Furthermore, the correlation between paO₂ and RVRR (r=-0.625, p<0.01) was also significant.
These results suggest that in cases with pulmonary diseases the right ventricle was compelled to perform less effective pumping function both in systole and diastole phase because of increased compliance of the right ventricle probably due to chronic hypoxia. This fact was further supported by acutely induced hypoxia test.

View full abstract

A new non- invasive measurement of cardiac performance, viz., intratracheal cardiogram or ITCG, which we introduced for the first time (Jap. J. Anesthesiol., 25: 357, 1976 & 26: 436, 1977.), is based on the airflow or pressure change in the trachea of apneic anesthetized intubated patients produced by cardiogenic oscillation and measured by means of a highly sensitive pressure transducer or pneumotachograph.
Since the resonant frequency of the system with the previous pressure transducer was found inadequate for correctly assessingspike waves of ITCG, a new pressure transducer (PM-25) was recently developed the resonant frequency of which proved to be sufficient (about 195Hz) for this purpose.
Some of the parameters calculated from the spike waves of ITCG obtained by means of the new transducer with reference to ECG, i. e. QC, BC, QB, & QB. BC ratio were compared to known indices of systolic time intervals obtained by the ordinary non-invasive method, i. e. EMS, LVET, PEP, & PEP. LVET ratio.
Mean values and relationships with heart rate of the corresponding parameters and indices of the two methods, as well as correlation coefficients and regression equations between the corresponding parameters and indices of the two methods showed no significant difference statistically.
Therefore ITCG is expected to be useful in evaluating non-invasively cardiac performance of intubated patients during anesthesia or under intensive care.
Some problems about the assessment of ITCG spike waves and the ITCG generation mechanism are also discussed.

View full abstract

A 45 year-old housewife was admitted to our hospital on October 25, 1976 with reccurent exertional dyspnea.
Since 5 years ago, she began to notice dyspnea on exertion in the summer or autumn of each year.
Chest X ray showed interstitial infiltrate in both lower lung fields and pulmonary function tests showed lowered D_LCO and hypoxemia.
Histopathologic findings of the specimen obtained by open lung biopsy performed November 14, 1975 showed granulomas scattered in the parenchyma and a diagnosis of hypersensitivity pneumonitis was made.
Precipitating antibodies to various antigens could not be detected.
The symptoms subsided after administration of prednisone and the patient has been well since then.

View full abstract