Biomedical subjects

T Takishima

Publications and source records attributed to T Takishima.

At least 19 recordsLinked to original sources

PubMed1992

Protection against bradykinin-induced bronchoconstriction in asthmatic patients by neurokinin receptor antagonist.

Axon reflex mechanisms may be involved in the pathogenesis of asthma, but there has been no direct evidence that endogenous tachykinins cause bronchoconstriction in asthmatic subjects. We have studied the effect of a tachykinin receptor antagonist (FK-224) on bronchoconstriction induced by inhalation of bradykinin in asthmatic patients. In a double-blind, placebo-controlled, crossover trial, ten subjects with stable asthma were given FK-224 (4 mg) or placebo by inhalation 20 min before challenge with bradykinin (0-1250 micrograms/ml, five breaths of each concentration) given with 5 min intervals. Bradykinin caused dose-dependent bronchoconstriction in all subjects. FK-224 significantly opposed the bronchoconstrictor effect; the geometric mean of the cumulative concentration required to elicit a 35% fall in specific airway conductance was 5.3 micrograms/ml after placebo and 40 micrograms/ml after FK-224 (p < 0.001). Inhalation of bradykinin caused coughing in three subjects, which was inhibited by FK-224 in all three. Antagonism of the tachykinin receptor by FK-224 greatly inhibited both bronchoconstriction and coughing induced by bradykinin in asthmatic patients, suggesting that tachykinin release from the airway sensory nerves is involved in responses to bradykinin. Tachykinin receptor antagonists may be useful in the treatment of asthma.

Administration, Inhalation↗

PubMed1992

Functional analysis of alternatively spliced transcripts of the human histidine decarboxylase gene and its expression in human tissues and basophilic leukemia cells.

L-Histidine decarboxylase (HisDC) is the enzyme catalyzing the formation of histamine from L-histidine. HisDC activity is expressed specifically in mast cells/basophils, endocrine cells in stomach, and histaminergic neurons in brain. As a first step in the analysis of the regulation of HisDC gene expression, we have cloned the cDNA coding for HisDC from a cDNA library of a human basophilic leukemia cell line, KU-812-F. We identified two types of HisDC cDNA, representing the 2.4-kb and 3.4-kb HisDC mRNA constitutively expressed in these cells. Sequence analysis of these cDNA revealed that the 3.4-kb mRNA contains the insert sequence of 824 bases and suggests that both 2.4-kb and 3.4-kb mRNA may represent the alternatively spliced transcripts of the HisDC gene. Using expression plasmids containing a cDNA for each HisDC mRNA, we analyzed the function of possible HisDC isoforms. We show that only the 2.4-kb mRNA encodes functional HisDC and is expressed in human brain and lung. However, we were unable to detect the 3.4-kb mRNA in these tissues. Thus, the 3.4-kb mRNA may be generated by KU-812-F cell-specific splicing of the HisDC gene transcripts. Furthermore, we demonstrated the increase in the level of 2.4-kb HisDC mRNA and HisDC activity in KU-812-F cells following treatment with phorbol 12-myristate 13-acetate.

Alternative Splicing↗

PubMed1992

Evidence that an atypical beta-adrenoceptor mediates the prejunctional inhibition of non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

We investigated the effect of the putative beta 3 agonist BRL 35135 on non-adrenergic non-cholinergic (NANC) contractions in guinea-pig bronchial strips. BRL 35135 (10(-9) to 10(-6) M) did not alter the baseline tension but reduced NANC contractions induced by electrical field stimulation (EFS) in a concentration-dependent fashion without having a significant effect on the contraction induced by substance P (10(-6) M). BRL 35135 (10(-6) M) also reduced the contraction induced by capsaicin (10(-7) M). Likewise, BRL 37344 (10(-9) to 10(-6) M) reduced NANC contractions induced by EFS in a concentration-dependent fashion. While BRL 37344 up to concentrations of 10(-8) M did not alter the contraction induced by SP (10(-6) M), BRL 37344 (10(-8) M) significantly inhibited NANC contractions induced by EFS and capsaicin (10(-7) M), (P less than 0.01). The inhibitory effect of BRL 35135 (10(-6) M) on NANC contractions induced by EFS was not significantly altered by the non-selective beta-adrenoceptor antagonists, propranolol and pindolol (P greater than 0.10), by the beta 1-selective antagonists, atenolol and metoprolol (P greater than 0.20) (10(-8) to 10(-6) M), or by the alpha-adrenoceptor antagonist, phentolamine (10(-7) to 10(-5) M) (P greater than 0.50). These results suggest that beta 3 agonists exert a prejunctional inhibitory action on NANC contractions.

Animals↗

PubMed1992

Inhibitory actions of prostaglandin E1 on neurogenic plasma extravasation in rat airways.

To determine whether neurogenic inflammation can be inhibited by prostaglandin E1 (PGE1), that is suggested to have an inhibitory effect on neuropeptide release from airway sensory nerves, we examined plasma extravasation in the airways of anesthetized rats in vivo with Evans blue due as a marker. Neurogenic inflammation was produced by an i.v. injection of capsaicin (100 micrograms/kg) or by antidromic electrical stimulation of the right vagus nerve (4 Hz, 1 ms, 4 V for 1 min). Capsaicin injection significantly increased leakage of dye in the trachea and main bronchi. Similar increases in leakage were seen in the trachea and right bronchus on electrical stimulation of the right vagus nerve. PGE1 (1-1000 micrograms/kg) inhibited the leakage induced by capsaicin in the trachea and bronchi concentration dependently with complete inhibition at a concentration of 1000 micrograms/kg. Likewise, PGE1 (1000 micrograms/kg) significantly inhibited electrical stimulation-induced leakage in the trachea and right bronchus (P less than 0.01). I.v. substance P (SP; 1 microgram/kg) increased Evans blue dye extravasation in the same way as the leakage induced by capsaicin and electrical stimulation but PGE1 (1000 micrograms/kg) failed to inhibit SP-induced leakage in the trachea and main bronchi (P greater than 0.20). These results suggest that PGE1 inhibits neurogenic plasma leakage by presynaptic inhibition of the release of neuropeptides from sensory nerves.

Alprostadil↗

PubMed1992

Maximum stress-volume index ratio of the left ventricle in hypertrophic cardiomyopathy.

To evaluate the left ventricular contractile state in patients with nonobstructive hypertrophic cardiomyopathy (HCM), we analyzed the maximum stress-volume index ratio (MSVR) using catheter-tip cineangiography in 11 patients with HCM and 16 normal subjects. The value of the MSVR in normal subjects was 6.48 +/- 1.25 kdyn/cm5/m2 (mean +/- SD) and we defined the range of the mean +/- 2 SD as the normal MSVR range. Six patients with HCM placed inside the normal MSVR range (IN), but the other 5 patients placed outside and to the right of the normal range (RIGHT). This suggests that the contractile states of the patients of the RIGHT group were depressed. Compared with IN, the end-diastolic and end-systolic volume indices of RIGHT were larger (EDVI; 69.3 +/- 6.9 vs. 96.1 +/- 11.1 ml/m2, p less than 0.01, ESVI; 18.2 +/- 3.2 vs. 29.1 +/- 8.3 ml/m2, p less than 0.05), but the ejection fraction did not differ (IN 73.5 +/- 5.7 vs. RIGHT 69.6 +/- 8.3%, NS). End-diastolic pressure of IN and RIGHT was higher than that of normal subjects (IN 16.5 +/- 4.5, RIGHT 16.7 +/- 4.6 vs. 8.3 +/- 2.5 mm Hg, both p less than 0.05), but there was no difference between the two groups in HCM. End-systolic pressure did not differ among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Opsonized zymosan decreases cytoplasmic motility of alveolar macrophages in dogs.

To examine the mechanisms of changes in alveolar macrophage (AM) activities caused by phagocytic stimulus, we studied the effect of opsonized zymosan (OZ) on cytoplasmic motility (CM) of AM from dog lungs in vitro. Four days after the instillation of ferrimagnetic particles (Fe3O4, 3 mg/kg) into the lower lobe bronchus, AM were harvested by broncho-alveolar lavage. AM were adhered to the bottom of plastic vials (10(6) cells of AM per each vial). Remanent field strength (RFS) from the AM containing Fe3O4 particles was measured immediately after magnetization. RFS decreased with time due to particle rotation (relaxation), which is related to cytoplasmic motility of AM. OZ (1-500 micrograms) decreased lambda 0 (the relaxation rate for the first min) in a concentration-dependent fashion. Neither BW755C (10(-5) M), indomethacin (10(-6) M), leupeptin (10(-5) M), bestatin (10(-5) M), nor superoxide dismutase (1000 U/ml) inhibited OZ (500 micrograms)-induced inhibitory effects on lambda 0, suggesting that cyclooxygenase and lipoxygenase products, serine, thiol enzymes, aminopeptidase and superoxide anion wer not responsible for OZ-induced effects. OZ (500 micrograms) significantly increased the intracellular concentration of Ca2+ (P less than 0.01). Likewise, OZ (500 micrograms)-induced effects on lambda 0 of AM were significantly inhibited by replacement of the medium with a Ca2+ free solution (P less than 0.01). These results imply that opsonized zymosan inhibits cytoplasmic motility of AM via external calcium influx.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1992

Influence of lung volume history and increased surface forces on collateral resistance.

In order to investigate the major route for collateral ventilation, the influences of lung volume history and increased surface forces on collateral resistance (Rcoll) were studied in excised canine lower lobes. Measurements were made during inflation and deflation in two states, i.e. before (control) and after stiffening by large tidal ventilation raising peak recoil pressure (Ptp) by 8-10 cmH2O. Air flowed into a wedged segment via a double lumen catheter (Vcoll) keeping segmental pressure (PS) constant at 2 cmH2O as monitored through the other lumen, giving Rcoll = Ps/Vcoll. Rcoll vs lung volume (VL) showed little hysteresis, in sharp contrast to Rcoll vs Ptp (Rcoll higher during inflation). Thus, in each state, Gcoll (= 1/Rcoll) depended primarily on VL, but the stiffed state appeared to have permanently enlarged channels or recruited new ones. The relations between Gcoll and VL or Ptp somewhat resemble reported bronchial diameter behaviour. The ventilation process itself, rather than higher surface forces per se, appeared to distend collateral channels in the stiff lung. The results are consistent with the major component of Gcoll being located at the bronchiole level.

Airway Resistance↗

PubMed1992

Hypoxic contraction of pre-stretched human pulmonary artery.

To clarify the mechanism of hypoxic pulmonary vasoconstriction in man, human pulmonary artery segments (2 mm O.D.) were suspended and changes in isometric force were measured. The arteries were contracted by hypoxia (PO2 43 +/- 2 Torr) developing a tension of 127 +/- 36 mg over the course of 15 min. This contraction was completely blocked by 10(-6) M L-isoproterenol, 10(-6) M nitroglycerin, partially blocked by 10(-8)-10(-6) M verapamil, unchanged by 10(-6) M phentolamine, 10(-6) M L-propranolol, 10(-6) M diphenhydramine, 10(-6) M guanethidine, 10(-7) M FPL 55712 and enhanced by 10(-6) M BAY K 8644, 10(-3) M procaine, 3 x 10(-6) M quinacrine, 10(-6) M indomethacin or 10(-6) M methylene blue. Removal of the endothelium significantly enhanced the magnitude of hypoxia-induced contraction. These results suggest that the human pulmonary artery constricts in response to hypoxia, at least in part, through activation of the voltage-dependent Ca2+ channels and that neither alpha, beta, H1 receptors, the lipoxygenase pathway nor neural reflexes are involved. They also show that the endothelium is not required for hypoxic contraction and that its presence reduces sensitivity to hypoxia.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1992

Induction of granule release by intracellular application of calcium and guanosine-5'-O-(3-thiotriphosphate) in human eosinophils.

The roles of Ca and G proteins in granule release from human eosinophils were examined by use of a patch-clamp technique in single cells. The morphologic changes and the release of eosinophil peroxidase (EPO) from single cells were simultaneously observed. In addition, the expression of small molecular weight guanine nucleotide binding protein (small G protein) mRNA (smg p25A [rab 3] and smg p21 [rab 1]) was investigated. The intracellular application of Ca, 10 mumol/L, and guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), 100 mumol/L, induced fusion of EPO containing granules with the surface membrane, which was associated with a marked increase in membrane capacitance. Ca alone caused a rapid granule release at an early stage of cell dialysis, but most granules still remained in a cluster. GTP-gamma-S alone caused a gradual degranulation. Northern blot analysis revealed the definite expression of smg p21 mRNA with no appreciable expression of smg p25A. These results provide direct evidence of granule fusion by intracellular application of Ca and GTP-gamma-S. In addition, Ca dependent proteins and G proteins act cooperatively in granule release, and these proteins likely regulate the different processes of degranulation. Furthermore, a protein, encoded by smg p21, may be involved in the granule release process in human eosinophils.

Calcium↗

PubMed1992

Vascular permeability and airway narrowing during late asthmatic response in dogs treated with Metopirone.

Recently, we have developed an animal model of late asthmatic response (LAR) by treating naturally sensitized dogs to Ascaris suum antigen with the cortisol-synthesizing inhibitor, Metopirone. By using this animal model, we examined the contribution of edema in the airway wall to the development of LAR. To study whether airway microvascular leakage is increased in association with LAR, we performed antigen challenge in dogs treated with Metopirone. We measured the amount of extravasated Evans blue (EB) dye from the esophagus, trachea, and large and small bronchi 8 hours after the antigen challenge in dogs demonstrating immediate asthmatic response alone (IAR) and in dogs demonstrating both IAR and LAR. Airway responses to A. suum antigen were assessed by changes in respiratory resistance measured with the force oscillation technique at 3 Hz. EB dye extravasation did not increase significantly from that of control in any tissues in IAR (P greater than 0.10), but in LAR, it increased significantly from that of control (p less than 0.01) and IAR (p less than 0.05) in large and small bronchi. Histologic assessment of vascular permeability revealed that Monastral blue-labeled leaking vessels were only in sections from LAR, and leaking vessels were limited to small vessels (10 to 25 microns) in the trachea, large (diameter, greater than 5 mm) and small bronchi (2 to 4 mm in diameter), and bronchiole. The permeability index defined as the ratio of area of small vessels labeled with Monastral blue to that of the total small vessels in the walls was highest in the small bronchi. LAR significantly increased submucosal thickness of the small bronchi (p less than 0.05) compared with that in IAR. Both EB dye extravasation and permeability index in large and small bronchi also significantly increased during IAR within 3 minutes after the antigen challenge (p less than 0.05), but IAR did not alter the submucosal thickness of the small bronchi. These results imply that the increase in vascular permeability and submucosal thickness, especially in small bronchi, may be an important factor in the pathogenesis of LAR.

Airway Obstruction↗

PubMed1992

Effects of duration of pressure overload on the reversibility of impaired coronary autoregulation in rats.

The aim of this study was to determine the effects of duration of pressure overload on the reversibility of impaired coronary autoregulation in hypertropied hearts. The experiments were performed on 38 anesthetized male Wistar rats aged 6 to 8 weeks. The ascending aorta was banded for 4 or 10 weeks, then in some rats the bands were removed for 4 weeks. We estimated coronary hemodynamics in a model consisting of isolated non-working hearts perfused with Tyrode's solution containing bovine red blood cells and serum albumin. Myocardial mass increased significantly in 4 and 10-week banded groups compared to controls. Four weeks after debanding in 4- and 10-week banded groups, the value returned to that of controls. Autoregulation gain was significantly lower in banded groups than in controls in the range between 50 and 100 mmHg of coronary perfusion pressure. Although the gain normalized in the debanded group after 4 weeks of banding, the value in the debanded groups after 10 weeks of banding remained less than zero between 25 and 150 mmHg of perfusion pressure. In transient flow response to a stepwise increase of perfusion pressure within the autoregulatory range, promptly increased flow was followed by more rapid and greater decrease in controls than in banded groups. The flow response regressed in the debanded group after 4 weeks of banding, while it remained unchanged in the debanded group after 10 weeks of banding. Thus, duration of pressure overload alters the regression of impaired coronary autoregulation in cardiac hypertrophy.

Animals↗

PubMed1992

Regional variation of excitatory and inhibitory amino acid-induced responses in rat dissociated CNS neurons.

Regional differences in glutamate (Glu), aspartate (Asp), gamma-aminobutyric acid (GABA) and glycine (Gly) responses in CNS neurons were investigated by means of the whole-cell mode of the patch-clamp technique. The neurons were freshly dissociated from rat cortex, limbic system (hippocampal CA1 region), diencephalon (ventromedial hypothalamus), medulla (nucleus paragigantocellularis lateralis) and spinal cord (spinal dorsal horn). The current amplitudes induced by Glu and GABA did not show any regional differences whereas those of Asp- and Gly-induced responses were significantly different among CNS regions. The enhancement of Asp response by Gly was observed in all regions, and the facilitatory ratio did not differ among these regions. Even though the NMDA response in cortical neurons was significantly greater than that in spinal neurons, the ratios of NMDA response facilitation by Gly were also the same in both regions. When the current amplitudes induced by individual amino acids were estimated for the unit surface area of respective neurons (current density), the Glu, Asp and Gly responses showed regional heterogeneity whereas the GABA response did not.

Amino Acids↗

PubMed1992

Effects of alpha and beta adrenergic blockade on coronary arterial microvessels in the beating canine heart.

OBJECTIVE: The aim was to clarify the effects of alpha and beta adrenergic blockade on coronary arterial microvessels and to assess the role of alpha and beta adrenergic tone in normally beating hearts. METHODS: 47 anaesthetised open chest dogs were studied. The diameters of epicardial arterial microvessels were measured in beating hearts using an incident light fluorescence microscope equipped with a floating objective. Drugs were infused into the left anterior descending coronary artery keeping the heart rate and aortic pressure at control levels. To examine the effect of alpha adrenergic blockade, phentolamine (100 micrograms.kg-1) was given in the absence or presence of beta adrenergic blockade (propranolol 50 micrograms.kg-1). To examine the effect of beta adrenergic blockade, propranolol (50 micrograms.kg-1) or three doses of ICI 118,551 (a selective beta 2 antagonist, 0.1, 0.5, and 1.0 microgram.kg-1.min-1) was given. RESULTS: Coronary arterial microvessels were divided into three groups according to the control diameters (D) of small (D less than 100 microns), medium (100 less than or equal to D less than 200 microns) and large (D greater than or equal to 200 microns) groups. In the absence of beta adrenergic blockade, phentolamine significantly dilated all vessel groups: small +19.6 (SEM 5.6)%, medium +5.8(2.3)%, large +5.3(0.9)%. In the presence of beta adrenergic blockade, the vasodilator effect of phentolamine was completely abolished. Propranolol constricted all vessel groups: small -3.6(1.1)%, medium -4.8(1.0)%, large -3.5(1.0)%. ICI 118,551 significantly constricted the large vessel group [-2.5(0.6)%] at the mid dose, and the medium and large vessel groups [medium -3.1(0.8)%, large -3.5(1.3)%] at the highest dose. CONCLUSIONS: These data indicate that (1) the vasodilator effect of phentolamine is induced by beta adrenergic stimulation; (2) resting alpha adrenergic tone of coronary arterial microvessels is minimal in normally beating hearts, and (3) resting beta adrenergic tone may play a physiological role in coronary arterial microvessels, and beta 2 adrenergic tone predominates in arterial microvessels greater than 100 microns in diameter.

Adrenergic alpha-Antagonists↗

PubMed1992

Effects of exercise stress on left ventricular end diastolic pressure-length strain relations in dogs with and without coronary stenosis.

OBJECTIVE: The aim was to elucidate the alterations of left ventricular diastolic properties, taking into account changes in unstressed length during exercise stimuli with and without coronary stenosis. METHODS: Left ventricular end diastolic pressure-length strain relations using segment length normalised to Lagrangian strain, and the rate of relaxation, were studied in seven open chest anaesthetised dogs with and without coronary stenosis on both left anterior descending and circumflex coronary arteries (approximately 30% resting flow reduction) during simulated dynamic exercise. Regional segment length was measured with ultrasonic crystals placed in the left anterior descending subendocardial region, and unstressed segment length at zero transmural pressure was obtained by occluding the vena cava. RESULTS: Peak negative dP/dt was decreased and isovolumetric left ventricular relaxation time constant increased by coronary stenoses; however neither changed significantly during simulated exercise. Left ventricular end diastolic pressure was significantly increased by coronary stenoses, from 3.1(SEM 0.8) to 7.0 (0.9) mm Hg (p < 0.05), and further increased to 15.5(1.1) mm Hg (p < 0.01) during simulated exercise, although right ventricular end diastolic pressure did not change. Unstressed length was increased in coronary stenoses from 9.03(0.08) to 9.89(0.13) mm (p < 0.01), and further increased to 10.34(0.14) mm (p < 0.01) during exercise, whereas it tended to decrease without coronary stenosis, from 9.03(0.08) to 8.79(0.11) mm during exercise. Left ventricular end diastolic pressure-length strain relations progressively shifted upward and leftward with coronary stenoses and subsequent exercise, but shifted downward and rightward during exercise without coronary stenosis. CONCLUSIONS: The increase in unstressed length or volume may contribute to exercise induced left ventricular dilatation observed in patients in effort angina. End diastolic distensibility decreases in both mild supply induced and exercise induced ischaemia, whereas in the normal heart, left ventricular end diastolic distensibility increases during exercise.

Animals↗

PubMed1992

Value of three-dimensional surface display of brain perfusion imaging. Comparison with tomographic imaging.

The diagnostic ability of a three-dimensional surface display of I-123 IMP brain scintigrams and tomographic images was compared in 12 patients who underwent I-123 brain tomography for cerebral cortical hypoperfusion. Foci of decreased accumulation were independently diagnosed by four radiologists, first with transaxial images, second with three-dimensional images, and finally with both images subjectively compared for the purpose of diagnosing the existence, localization, and extent of lesions. Six different lesions (0 to 3 lesions/radiologist) were found only on the transaxial images, but 30 different lesions (1 to 14 lesions/radiologist) were found on the three-dimensional images. In 9 out of 12 cases, the three-dimensional images were regarded as superior for evaluating the extension of the lesion and for lesion existence and lesion localization in 5 out of 12 (P less than 0.05). In conclusion, a three-dimensional display of an I-123 IMP brain tomogram is superior to tomographic images in diagnosing the extent of cerebral cortical hypoperfusion. However, the display is not superior to tomographic images for diagnosing the existence and localization of hypoperfusion.

Amphetamines↗

PubMed1992

The role of cyclic AMP in non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

1. We investigated the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in non-adrenergic non-cholinergic (NANC) contraction in guinea-pig bronchial strips. 2. Forskolin (3 nM to 1 microM) reduced NANC contraction induced by electrical field stimulation (EFS) in a concentration-dependent fashion (-log EC50 was 7.22 +/- 0.12 M and maximum inhibition was 100 +/- 0.01%). However, forskolin (less than 1 microM) did not alter the contraction induced by substance P (SP, 1 microM). 3. Dibutyryl cyclic AMP (1 mM) also reduced NANC contractions induced by EFS (100 +/- 0.01%) without significant effect on SP (1 microM)-induced contractions. In contrast, dibutyryl cyclic GMP (1 mM) was without effect against either NANC or SP-induced contractions. 4. Both the beta 2-adrenoceptor agonist, procaterol (0.1 nM to 3 nM) and theophylline (100 nM to 1 mM) concentration-dependently reduced EFS-induced NANC contractions without significant effect on SP (1 microM)-induced contractions. 5. In contrast to forskolin, procaterol and theophylline, both sodium nitroprusside and cromakalim inhibited the EFS-induced contractions only at those concentrations that similarly reduced the contractions induced by SP (1 microM). 6. These results suggest that cyclic AMP may mediate pre-junctional inhibition of NANC contractions in guinea-pig bronchi.

Animals↗

PubMed1992

Effects of posture on flow-volume curves during normocapnia and hypercapnia in patients with obstructive sleep apnoea.

BACKGROUND: A high ratio of forced expiratory to forced inspiratory maximal flow at 50% of vital capacity (FEF50/FIF50) may identify upper airway dysfunction. Since hypercapnia increases the motor activity of airway dilating muscles its effects on the maximum expiratory and inspiratory flow-volume curves (MEIFV) in patients with obstructive sleep apnoea and in normal subjects in different postures was studied. METHODS: The effects of posture on the maximum expiratory and inspiratory flow-volume curves during the breathing of air and 7% carbon dioxide in 11 patients with obstructive sleep apnoea were compared with those in nine normal subjects. Measurements were made in the sitting, supine, and right lateral recumbent positions. Forced expiratory flow at 50% vital capacity (FEF50), forced inspiratory flow at 50% vital capacity (FIF50) and FEF50/FIF50 were determined. RESULTS: In the normal subjects FEF50, FIF50, and FEF50/FIF50 were not affected by change in posture or by breathing carbon dioxide. In the patients there was a fall in FIF50 and an increase in FEF50/FIF50 when breathing air in the supine position compared with values in the seated and lateral position. While they were breathing carbon dioxide there was a slight increase in FEF50 when patients were seated or in the lateral position compared with values during air breathing. Hypercapnia abolished the effects of posture on FEF50/FIF50. Values for FEF50/FIF50 in the supine position while they were breathing air correlated with the apnoeic index but not with other polysomnographic data. CONCLUSION: In patients with obstructive sleep apnoea the upper airway is prone to collapse during inspiration when the patient is supine, even when awake; this tendency can be reversed by breathing carbon dioxide.

Adult↗

PubMed1992

Modulatory role of EDRF in hypoxic contraction of isolated porcine pulmonary arteries.

To examine the hypothesis that suppression of basal release of endothelium-derived relaxing factor (EDRF) by hypoxia might be related to the mechanism of hypoxic pulmonary vasoconstriction, rings of porcine pulmonary artery (PA, 2 mm OD) were suspended in organ chambers and changes in isometric force were measured. Hypoxia significantly reduced endothelium-dependent relaxation induced by acetylcholine and augmented contractile response to phenylephrine. This augmentation by hypoxia was not seen in rings without endothelium. Contractile response to phenylephrine was also enhanced by removal of endothelium. With 15 min of hypoxia, PA contracted and guanosine 3',5'-cyclic monophosphate content decreased. Pretreatment with 10(-6) M methylene blue, 3 x 10(-7) M oxyhemoglobin, and 9.6 x 10(-5) M NG-monomethyl-L-arginine significantly enhanced hypoxic contraction. Furthermore, removal of endothelium also enhanced hypoxic contraction. These results suggest that suppression of basally released EDRF by hypoxia was not the cause of the contractile response to hypoxia and that EDRF modulates the hypoxic contraction of porcine PA in basal conditions at this diameter.

Acetylcholine↗