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Biomedical subjects

M Okazawa

Publications and source records attributed to M Okazawa.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of chronic antigen and beta 2 agonist exposure on airway remodeling in guinea pigs.

We recently reported that chronic exposure to fenoterol (FEN) in guinea pigs increases in vivo and in vitro airway responsiveness to a degree similar to that induced by chronic antigen (ovalbumin [OA]) exposure. We hypothesized that these changes were due to airway inflammation and airway remodeling. To trace newly recruited granulocytes as a marker of inflammation and to detect DNA replication in resident airway wall cells, the nucleotide 5'-bromo-2'-deoxyuridine (BrdU) was administered intermittently over the six-wk period of chronic FEN and/or OA exposure. Noncartilaginous airway dimensions were measured and the area fraction of BrdU-immunoreactive and total nuclei in adventitia, smooth muscle, and epithelium was determined by immunohistochemistry and point counting. The proliferation index was defined as the ratio of the two area fractions in each wall area. The adventitial areas of FEN- and OA-treated airways were respectively 62 and 88% greater than those of control airways (p < 0.05). The inner wall areas were not increased. The smooth muscle cell and epithelial cell proliferation index was increased after OA (smooth muscle index: control, 2.7 +/- 1.1% [SEM]; OA, 23.0 +/- 3.7%; p < 0.02) but not after FEN exposure, and there was an increased number of BrdU-immunoreactive granulocytes in the adventitia and epithelium after OA but not after FEN exposure. The increased in vivo airways responsiveness produced by chronic OA or FEN exposure may be attributable to adventitial thickening and increased in vitro muscle contractility, but the cellular mechanisms underlying these and other airway wall responses are different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1994

Proposed nomenclature for quantifying subdivisions of the bronchial wall.

There is increasing interest in the structural components of the airway wall because of the airway remodeling that is observed in conditions such as asthma and chronic obstructive pulmonary disease and because of their contribution to changes in airway mechanics. This interest has stimulated several groups to make morphometric measurements on airway cross sections, and their results have been reported using a variety of nomenclature. We propose the adoption of a standard system of nomenclature that is based on accepted terms for subdivisions of the airway wall and has been agreed to by several groups working in this field.

Bronchi↗
PubMed1993

Airway smooth muscle shortening in excised canine lung lobes.

To estimate the importance of lung parenchymal airway interdependence in attenuating airway narrowing, airway smooth muscle shortening in response to nebulized carbachol was measured in excised canine lung lobes and compared with the calculated load applied by lung elastic recoil. Pulmonary resistance of matched right and left upper lobes of five dogs was measured in a pressure-compensated volume plethysmograph by forced oscillation (6 Hz) before and after administration of an aerosol of carbachol (250 mg/ml) or saline. Matched lobes were studied at transpulmonary pressures (PL) of 5, 7, 10, 12, and 15 cmH2O. The lungs were then fixed at that PL by pulmonary arterial perfusion with formaldehyde, and cross sections of multiple airways from each lobe (n = 275) were examined by use of morphometric techniques to measure luminal area and smooth muscle length. By use of the saline lobe as a control, percentage of muscle shortening and decrease in airway lumen area caused by carbachol could be calculated. Passive and active smooth muscle stresses in each airway were calculated from PL and the calculated change in peribronchial pressure for a given change in airway diameter. The increase in pulmonary resistance and average smooth muscle shortening after administration of carbachol was greater in lobes held at lower PL. There was marked variation in narrowing between airways within a lobe: smooth muscle shortening ranged between 0 and 65% but averaged < 45% at all levels of PL.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1992

In vivo loads on airway smooth muscle: the role of noncontractile airway structures.

The degree of airway smooth muscle contraction and shortening that occurs in vivo is modified by many factors, including those that influence the degree of muscle activation, the resting muscle length, and the loads against which the muscle contracts. Canine trachealis muscle will shorten up to 70% of starting length from optimal length in vitro but will only shorten by around 30% in vivo. This limitation of shortening may be a result of the muscle shortening against an elastic load such as could be applied by tracheal cartilage. Limitation of airway smooth muscle shortening in smaller airways may be the result of contraction against an elastic load, such as could be applied by lung parenchymal recoil. Measurement of the elastic loads applied by the tracheal cartilage to the trachealis muscle and by lung parenchymal recoil to smooth muscle of smaller airways were performed in canine preparations. In both experiments the calculated elastic loads applied by the cartilage and the parenchymal recoil explained in part the limitation of maximal active shortening and airway narrowing observed. We conclude that the elastic loads provided by surrounding structures are important in determining the degree of airway smooth muscle shortening and the resultant airway narrowing.

Animals↗
PubMed1992

Effect of vagal stimulation and parenteral acetylcholine on canine trachealis muscle shortening.

Canine trachealis smooth muscle shortening (TMS) in response to vagal nerve stimulation is approximately 30%, far less than the 70% predicted from in vitro studies. We hypothesized that in vivo airway smooth muscle activation during vagal stimulation may be submaximal, and in this study we wished to determine TMS during maximal activation. TMS was studied in 12 alpha-chloralose-anesthetized dogs during vagal stimulation, systemic acetylcholine injection, and local acetylcholine injection. Bilateral vagal stimulation produced TMS of 26 +/- 5% (SE) length at functional residual capacity (LFRC). Maximal TMS during systemic injection of acetylcholine was 28 +/- 12% LFRC but may have been limited by delivery of acetylcholine to the muscle because asystole occurred at higher concentrations. TMS was greatest during local injection of acetylcholine (48 +/- 7% LFRC). There was a greater increase in pulmonary resistance and decrease in dynamic compliance during systemic acetylcholine injection than during vagal stimulation. We conclude that bilateral vagal nerve stimulation does not maximally activate trachealis smooth muscle but that the maximal shortening achieved with local injection of acetylcholine is still less than isotonic shortening in vitro. These data suggest that maximal shortening in vivo is limited by the afterload provided by the tracheal cartilaginous rings.

Acetylcholine↗
PubMed1992

Airway narrowing in excised canine lungs measured by high-resolution computed tomography.

The exact site of airway narrowing in asthma and chronic obstructive pulmonary disease is unknown. High-resolution computed tomography (HRCT) is a sensitive noninvasive imaging technique that can be used to measure airway dimensions. After determining the optimal computed tomographic parameters using a phantom, we measured lobe volume and airway dimensions of isolated canine lung lobes at a transpulmonary pressure of 25 cmH2O. These measurements were repeated after deflation and administration of aerosolized saline and carbachol (256 mg/ml). Lobe volume decreased with all treatments. The maximal lobar volume change was 26% at 6 cmH2O after carbachol. Average airway lumen area decreased with all treatments. After carbachol, at transpulmonary pressures of 25, 15, 10, 8, and 6 cmH2O, lumen area decreased by 7.3 +/- 4.1, 62.0 +/- 4.9, 77.5 +/- 3.0, 31.9 +/- 9.0, and 95.2 +/- 1.0% (SE), respectively. When the airways were divided into four categories on the basis of initial lumen diameter (less than 2, 2-4, 4-6, and greater than 6 mm), the greatest decreases in luminal area after carbachol were seen in intermediate-sized airways (2-4 mm, 56 +/- 4%; 4-6 mm, 59 +/- 3%). HRCT can be used to make accurate measurements of airway dimensions and airway narrowing in excised lungs. HRCT may allow measurement of airway wall thickness and determination of the site of airway narrowing in asthma.

Administration, Inhalation↗
PubMed1992

In vivo and in vitro correlation of trachealis muscle contraction in dogs.

Maximal trachealis muscle shortening in vivo was compared with that in vitro in seven anesthetized dogs. In addition, the effect of graded elastic loads on the muscle was evaluated in vitro. In vivo trachealis muscle shortening, as measured using sonomicrometry, revealed maximal active shortening to be 28.8 +/- 11.7% (SD) of initial length. Trachealis muscle preparations from the same animals were studied in vitro to evaluate isometric force generation, isotonic shortening, and the effect of applying linear elastic loads to the trachealis muscle during contraction from optimal length. Maximal isotonic shortening was 66.8 +/- 8.4% of optimal length in vitro. Increasing elastic loads decreased active shortening and velocity of shortening in vitro in a hyperbolic manner. The elastic load required to decrease in vitro shortening to the extent of the shortening observed in vivo was similar to the estimated load provided by the tracheal cartilage. We conclude that decreased active shortening in vivo is primarily due to the elastic afterload provided by cartilage.

Animals↗
PubMed1992

Anterotracheal temperature during and after exercise in the guinea pig.

We measured the temperature in the anterotracheal region of the guinea pig during and after various intensities of exercise (from 20 to 100 m/3 min). The temperature decreased during exercise, and the maximal drop of the temperature increased with increasing intensity of exercise up to a speed of 80 m/3 min. When the exercise was discontinued, the temperature initially fell rapidly, then rose progressively to equal or exceed the preexercise value. The changes in temperature were similar among 5 animals. These findings suggest that the tracheal wall temperature changes during and after exercise relative to the intensity of exercise. Using this method in guinea pigs may provide more information about the pathophysiology of exercise-induced asthma.

Animals↗
PubMed1992

High-resolution computed tomography of experimental hydrostatic pulmonary edema.

To better understand the distribution and clearance mechanisms of extravascular lung water (EVLW) in pulmonary edema, computed tomographic (CT) scans of isolated canine lungs were obtained. In this model, there is no active lymphatic drainage. Fourteen isolated lobes were inflated with oxygen, and edema was induced by infusion of normal saline solution. Two volumes of saline were used, 50 percent and 150 percent of initial wet lobar weight. Six 10-mm- and 1.5-mm-collimation CT scans were obtained at 10-mm intervals from the hilum to the periphery of the lobe before and after each of the two stages of pulmonary edema. The CT scans were reviewed independently by two chest radiologists and were assessed by CT densitometry. Both subjective analysis and CT densitometry showed a predominantly central peribronchial distribution of EVLW in the isolated lungs. Airway wall thickness also increased from the control value (average thickness, 1.0 mm) to 150 percent edema (average thickness, 1.5 mm) (p less than 0.001). We postulate that the peribronchial distribution of fluid is due to a pressure gradient from the alveolar interstitium to the interstitium around the blood vessels and airways at the hilum. This gradient may play a major role in the characteristic perihilar and peribronchial distribution of EVLW seen radiologically in patients with hydrostatic pulmonary edema.

Animals↗
PubMed1992

[Clinical efficacy of ceftriaxone when administered once daily for respiratory tract infections in patients with advanced ages].

Ceftriaxone (CTRX), a new third generation cephalosporin, was investigated upon once daily administration for its clinical efficacy and safety on respiratory tract infections in patients with advanced ages. The results are summarized as follows: 1. Clinical responses to CTRX of 48 cases of advanced age patients with respiratory tract infections were good with an efficacy rate of 89.6%. 2. Adverse reactions to CTRX were mainly exanthema in 7 cases (14.6%). 3. Serum levels of CTRX were determined in 4 cases after intravenous drip infusion of 2 g CTRX. Serum levels were analyzed by one-compartment model. There was no evidence of accumulation of CTRX in the patients with advanced ages.

Aged↗
PubMed1990

Effect of nifedipine administration on pulse wave velocity (PWV) of chronic hemodialysis patients--2-year trial.

Pulse wave velocity (PWV) is known to reflect the stiffness of the aorta, one of the major features of atherosclerosis. To clarify the severity and progression mechanism of atherosclerosis in hemodialysis patients and the preventive effect of nifedipine, PWV was annually measured for 2 years, and the change of PWV and contributory factors were analyzed. PWV in hemodialysis patients was faster than in age-matched normal controls. PWV was correlated with the duration of hemodialysis. delta PWV, which is obtained from the difference in PWV over 1 year, was positively correlated with age, high blood pressure, and serum cholesterol levels and was negatively correlated with HDL levels. The Ca x Pi value was also positively correlated with delta PWV. Nifedipine was administered to 47 patients for 2 years, and the change of PWV was compared with age-matched control hemodialysis patients. The PWV of the control group was gradually increased by 10%. The PWV of the group given nifedipine decreased by 2%. These results suggested that administration of nifedipine may prevent the progression of PWV in hemodialysis patients and may decrease the progression of atherosclerosis.

Adult↗
PubMed1990

Tracheal smooth muscle mechanics in vivo.

We applied the technique of sonomicrometry to directly measure length changes of the trachealis muscle in vivo. Pairs of small 1-mm piezoelectric transducers were placed in parallel with the muscle fibers in the posterior tracheal wall in seven anesthetized dogs. Length changes were recorded during mechanical ventilation and during complete pressure-volume curves of the lung. The trachealis muscle showed spontaneous fluctuations in base-line length that disappeared after vagotomy. Before vagotomy passive pressure-length curves showed marked hysteresis and length changed by 18.5 +/- 13.2% (SD) resting length at functional residual capacity (LFRC) from FRC to total lung capacity (TLC) and by 28.2 +/- 16.2% LFRC from FRC to residual volume (RV). After vagotomy hysteresis decreased considerably and length now changed by 10.4 +/- 3.7% LFRC from FRC to TLC and by 32.5 +/- 14.6% LFRC from FRC to RV. Bilateral supramaximal vagal stimulation produced a mean maximal active shortening of 28.8 +/- 14.2% resting length at any lung volume (LR) and shortening decreased at lengths above FRC. The mean maximal velocity of shortening was 4.2 +/- 3.9% LR.S-1. We conclude that sonomicrometry may be used to record smooth muscle length in vivo. Vagal tone strongly influences passive length change. In vivo active shortening and velocity of shortening are less than in vitro, implying that there are significant loads impeding shortening in vivo.

Animals↗
PubMed1990

Magnetic resonance imaging of hydrostatic pulmonary edema in isolated dog lungs: comparison with computed tomography.

Magnetic resonance imaging (MRI) is considered inferior to computed tomography (CT) in the assessment of lung parenchyma, being hampered by low proton density, magnetic susceptibility effects, flow, and cardiac and respiratory motion. In this study the authors assessed the potential usefulness of MRI by comparing it with corresponding CT images of the lung in the absence of motion. They studied eight excised normal canine lung lobes inflated with oxygen before and after induction of pulmonary edema produced by intravascular infusion of saline at 30 cm H2O. T1, T2 and proton density weighted, 5-mm thick, gapped, multislice sequences were performed at 1.5 T. Magnetic resonance images were compared with corresponding 5-mm collimation CT scans at identical levels both before and after the induction of pulmonary edema. The MR and CT scans were assessed independently by two chest radiologists. In normal lung, there was equivalent visualization of vessels down to 1 mm and bronchi to 2 mm in diameter. T1 and proton density scans demonstrated lower spatial resolution but greater contrast than the corresponding CT images. In pulmonary edema both T1 and proton density sequences demonstrated peribronchial edema with greater contrast than CT. Air-space filling was equally well demonstrated by either technique. The authors conclude that, in motionless lung, MRI has lower spatial but greater contrast resolution than CT. It is potentially superior to CT in assessing focal and diffuse lung disease if cardiac and respiratory motion artifacts can be minimized or suppressed.

Animals↗
PubMed1988

Hypertonic aerosol inhalation does not alter central airway blood flow in dogs.

Tracheobronchial blood flow in dogs increases with cold or dry air hyperventilation, possibly as a result of airway drying leading to increased osmolarity of airway surface fluid. This study was designed to examine whether administration of aerosols of various tonicity to alter airway surface fluid osmolarity would induce similar blood flow changes. Tracheobronchial blood flow was measured by the radioactive microsphere technique in six anesthetized dogs ventilated with warm humid air (100% relative humidity) for 15 min (period 1), air containing ultrasonically nebulized saline aerosol (1,711 mosmol/kg) for 3 min (period 2) and 12 min (period 3), and the same aerosol at a higher nebulizer output for a further 3 min (period 4). Between periods 3 and 4, the dogs were ventilated with warm humid air for 30 min to reestablish base-line conditions. In another five dogs, measurements were made after 30 min of ventilation with 1) warm humid air, 2) isotonic saline aerosol, 3) warm humid air, 4) distilled water aerosol (3 dogs), and hypertonic saline aerosol (2 dogs). After the last measurement was made, each dog was killed, the trachea and major bronchi were excised, and blood flow was calculated. No change in blood flow was found during any period of aerosol inhalation. The osmolar load imposed on the airways was estimated and was similar to that occurring during cold or dry air hyperventilation. These data suggest that increasing osmolarity of airway surface fluid does not explain the blood flow changes seen during hyperventilation of cold or dry air.

Aerosols↗
PubMed1985

The role of airflow in mucous transport in the trachea.

The role of airflow in mucous transport in the respiratory tract was studied. Seven mongrel dogs were tracheostomised at the caudal end of the neck, and the following two procedures were performed. In procedure (1), a small radiopaque plastic disc was placed on the mucous membrane of the right side wall of the trachea through the tracheostoma, which was then closed to let the dog breathe through the normal respiratory tract. Roentgenograms of the trachea were taken three times at 5-min intervals. Procedure (2) was designed to eliminate airflow from around the disc. A canula was placed in the trachea through the tracheostoma to bypass airflow, and the disc was placed on the mucous membrane slightly more proximal than the cannula. The transport rate was 11.1 +/- 4.1 mm/min (mean +/- S.D.) in procedure (1) and 5.4 +/- 2.7 mm/min in procedure (2), which showed a significant difference. The present results seem to indicate an important role of airflow in mucous transport in the trachea.

Animals↗