Hypoxemia and attenuated hypoxic ventilatory responses in mice lacking heme oxygenase-2: evidence for a novel role of heme oxygenase-2 as an oxygen sensor.
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Animals↗
Biomedical subjects
Wataru Hida
Publications and source records attributed to Wataru Hida.
Morphologic analyses of mandible and upper airway soft tissue by MRI of patients with obstructive sleep apnea hypopnea syndrome.
STUDY OBJECTIVES: To evaluate the morphological features of the mandible and the volume of the upper airway soft tissues in determining the anatomical risk factors for the upper airway in Japanese male patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Five morphological parameters of the mandible at the mandibular base plane and three volumetric parameters of the upper airway soft tissue were analyzed using three-dimensional (3D) magnetic resonance imaging software in 31 OSAHS and 20 controls. RESULTS: There were no significant differences between the two groups in mandibular internal width (the distance between the internal right and left gonia [IRG and ILG]) and mandibular bony thickness. However, the patients with OSAHS had a significantly wider mandibular divergence (the angle between the spina mentalis (SM)- IRG line and SM- ILG line), a smaller mandibular internal length (the perpendicular distance from SM to the RG- LG line), and a smaller area than the normal subjects at the mandibular base plane. There were no significant differences in these morphological parameters for the mandible between obese and nonobese OSAHS patients. The volumes of the tongue, soft palate, and lateral pharyngeal walls were not significantly different between the OSAHS and the control groups. CONCLUSIONS: Japanese male OSAHS patients had specific anatomical features in the bottom part of the mandible; however, obesity seemed to be a less significant risk factor. Investigators and clinicians must realize that ethnicity may modify the effects of obesity and abnormal craniofacial anatomy as risk factors for the pathogenesis of OSAHS.
Asian People↗
Characteristics of young-onset hypertension identified by targeted screening performed at a university health check-up.
Since the prevalence and clinical characteristics of young-onset hypertension are still to be elucidated, we performed targeted-screening at an annual university health check-up for two consecutive years. Out of 16,464 subjects in 2003 and 17,032 in 2004 that were aged less than 30 years, 22 and 26 students (all males) exhibited high blood pressure (BP), respectively, on three occasions during casual BP measurements at the Tohoku University Health Center (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively). These students were asked to measure their BP at home, and 9 subjects in total were diagnosed as having essential hypertension (EH). The remaining students were diagnosed as having white coat hypertension (WCH). In 8 out of 9 EH students, their father and/or mother had also been treated with antihypertensive medication. Adjustment by attendance ratio for each BP measurement suggested that the incidence of EH was around 0.1% and that of hypertension (EH and WCH) was around 0.5% in university students aged less than 25 years, since most of the subjects and hypertensive students were between 18 and 24 years old. Body mass index of the EH, which was more than 25 kg/m2 (overweight), was significantly higher than that with WCH. In conclusion, the combination of repeated casual BP measurements and home BP effectively identified young-onset EH. The clinical parameters indicated that male gender, genetic background, and excessive weight were risk factors for young-onset hypertension.
Adolescent↗
Mice with blunted hypoxic ventilatory response are susceptible to respiratory disturbance during hypoxia.
Hypoxia causes a life-threatening situation, and the ventilatory response to hypoxia plays an important role in preventing death. We have hypothesized that persons with a blunted hypoxic ventilatory response may have a weak defense response to hypoxic episodes and be susceptible to fatal respiratory disturbances. However, precise correlations between the hypoxic ventilatory response and respiratory disturbances are not well understood. In the present study we examined the hypoxic and hypercapnic ventilatory responses in nine inbred mouse strains (A/J, AKR/N, BALB/c, C3H/He, C57BL/6, DBA/2, NZW, SWR/J, and 129Sv). Breathing frequency, tidal volume and minute ventilation of unanesthetized and unrestrained mice were assessed by whole body plethysmography. Age-matched mice were exposed for 3 min to 10% O(2) in N(2) gas or 10% CO(2) in hyperoxic gas to determine the acute ventilatory response to chemical stimuli. Basal respiratory variables and hypoxic ventilatory responses differed among the strains, but the hypercapnic ventilatory response did not differ. The hypoxic ventilatory response was the highest in AKR/N mice and the lowest in SWR/J mice. These findings suggest that genetic factors may have influenced the hypoxic ventilatory response but not the hypercapnic ventilatory response. To examine the effects of severe hypoxic stress on the respiratory cycle, we exposed the strain with the highest or lowest hypoxic ventilatory response to 6% O(2) in N(2) until the onset of apnea. The "appearance time of apnea", which is defined as the time from the hypoxic loading to the onset of apnea, was shorter in the SWR/J strain than in the AKR/N strain. We suggest that a lower hypoxic ventilatory response may be a risk factor for apnea under hypoxia.
Adaptation, Physiological↗
Digital recording and analysis of esophageal pressure for patients with obstructive sleep apnea-hypopnea syndrome.
To evaluate sleep-related obstructive breathing events in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), we developed a technique for digital recording and analysis of esophageal pressure (Pes) and elucidated the Pes parameters. Pes was recorded overnight with a microtip-type pressure transducer in 74 patients with OSAHS. Simultaneously, in all patients digital polysomnography was recorded. The mean nadir end-apneic Pes swing (Pes Nadir) ranged from -20.2 to -147.4 cmH(2)O, with a mean of -53.6+/-2.9 cmH(2)O. Correlation of the mean Pes Nadir indicated a linear relationship with the mean ratio of maximal Pes swing to apnea duration (r(2)=0.70) and the mean area of the Pes (Pes Area) (r(2)=0.82). Significant correlations were noted between the mean Pes Nadir and apnea-hypopnea index (AHI, ranging from 7.9 to 109.5 per hour; r(2)=0.66), minimum SpO(2) (r(2)=0.60), oxygen desaturation index (ODI) of more than 3 (r(2)=0.65), arousal index (r(2)=0.54), and between the mean Pes Area and AHI (r(2)=0.63), minimum percutaneous arterial oxygen saturation (SpO(2); r(2)=0.57), ODI (r(2)=0.69), and arousal index (r(2)=0.41). Pes parameters were found to be significant in the evaluation of the severity of the respiratory effort during the sleep-related obstructive breathing events for patients with OSAHS.
Electroencephalography↗
Prevalence of chronic obstructive pulmonary disease in Japanese people on medical check-up.
In Japan, spirometry has not been included as an item in medical check-ups for all persons. The purpose of this study was to show evidence to recommend spirometry routinely on medical check-up for the early detection of chronic obstructive pulmonary disease (COPD). There were 12,760 enrolled persons who underwent medical check-up. COPD was defined as a ratio of forced expiratory volume in one second to slow vital capacity of 70% or less. We investigated the prevalence and its characteristics of COPD in people on medical check-up. The prevalence of COPD was 3.6% in all subjects, 4.5% in males, and 1.8% in females. In the comparison between males and females, the prevalence of COPD in males of most age groups was higher than that of females, and this difference was greater with aging. Males in their 50s and over 60 years old and females over 60 years old showed remarkably high prevalences. Occupations associated with a high smoking rate such as transportation-related occupations showed a higher prevalence of COPD. These results suggest that spirometry for all persons in medical check-ups can identify many COPD patients not aware of this disease. Spirometry should be carried out routinely on medical check-up.
Adult↗
Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2.
Heme oxygenase (HO) catalyzes physiological heme degradation and consists of two structurally related isozymes, HO-1 and HO-2. Here we show that HO-2-deficient (HO-2(-/-)) mice exhibit hypoxemia and hypertrophy of the pulmonary venous myocardium associated with increased expression of HO-1. The hypertrophied venous myocardium may reflect adaptation to persistent hypoxemia. HO-2(-/-) mice also show attenuated ventilatory responses to hypoxia (10% O2) with normal responses to hypercapnia (10% CO2), suggesting the impaired oxygen sensing. Importantly, HO-2(-/-) mice exhibit normal breathing patterns with normal arterial CO2 tension and retain the intact alveolar architecture, thereby excluding hypoventilation and shunting as causes of hypoxemia. Instead, ventilation-perfusion mismatch is a likely cause of hypoxemia, which may be due to partial impairment of the lung chemoreception probably at pulmonary artery smooth muscle cells. We therefore propose that HO-2 is involved in oxygen sensing and responsible for the ventilation-perfusion matching that optimizes oxygenation of pulmonary blood.
Animals↗
The effect of upper airway structural changes on central chemosensitivity in obstructive sleep apnea-hypopnea.
We examined the efficiency of upper airway structural changes in uvulopalatopharyngoplasty and/or tonsillectomy on central chemosensitivity, and whether the outcome of such surgeries can be predicted by the central chemosensitivity in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. In 11 patients with OSAHS group, the average of the hypercapnic ventilatory response (HCVR) slope was 1.93 +/- 0.20 L/min/mm Hg preoperatively and 1.78 +/- 0.22 L/min/mm Hg postoperatively. The average of the mouth occlusion pressure at 0.1 second after the onset of inspiration (P (0.1)) slope was 0.47 +/- 0.06 cm H (2)O/mm Hg and 0.44 +/- 0.08 cm H (2)O/mm Hg, before and after surgery, respectively. There were no significant differences before and after treatment, although OSAHS was improved by these surgeries. In control group with 5 patients, the HCVR slope and P (0.1) slope also showed no significant difference before and after the procedure. When we divided the 11 OSAHS patients into 7 responders (apnea-hypopnea index < 20 events/h and > 50% reduction) and 4 poor responders, there was a significant difference between the average HCVR slope of responders (1.59 +/- 0.21 L/min/mm Hg) and that of poor responders (2.52 +/- 0.20 L/min/mm Hg). We saw no significant difference in physiologic (age, body mass index, one-piece tonsil weight), blood gas values, cephalometric, spirometric, or sleep parameters.
Adult↗
Improved activities of daily living, psychological state and health-related quality of life for 12 months following lung volume reduction surgery in patients with severe emphysema.
OBJECTIVE: The aim of the present study was to evaluate the effect of lung volume reduction surgery (LVRS), with an emphasis on improvement in activities of daily living (ADL), psychological state and health-related quality of life (HRQL), for 12 months in patients with severe emphysema. METHODOLOGY: Eighteen male patients (mean age +/- SD: 65.2 +/- 6.4 years) who underwent LVRS following pulmonary rehabilitation (LVRS group) and 12 patients (67.0 +/- 8.1 years) who were medicated and underwent pulmonary rehabilitation (non-LVRS group) were studied. LVRS was performed by video-assisted thoracoscopic surgery. Serial measurements of lung function, 6-min walking distance (6MWD), ADL, HRQL and psychological state scores were performed before surgery and 3, 6, and 12 months after surgery (in the LVRS group), or on the day of discharge (in the non-LVRS group). RESULTS: As well as an improvement in FEV(1) and 6MWD, ADL scores were significantly improved in the items of 'face washing and teeth brushing', and 'indoor walking' at 3 months after LVRS (P < 0.05). At 12 months, an improvement was still found in 'indoor walking' and 'bathing'. HRQL scores were ameliorated at 3-12 months after LVRS. In the non-LVRS group, ADL and HRQL scores failed to improve in any items during the 12 months of observation. Psychological state scores were maintained in the LVRS group and were better than those in the non-LVRS group at 12 months (P < 0.05). CONCLUSIONS: Lung volume reduction surgery improves not only lung function and exercise performance but also ADL, HRQL and psychological state for at least 12 months.
Activities of Daily Living↗
Bach1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells.
Heme oxygenase 1 (HO-1) catalyzes heme breakdown, eventually releasing iron, carbon monoxide, and bilirubin IXalpha. HO-1 is induced by its substrate heme and various environmental factors, which represents a protective response against oxidative stresses. Here we show that hypoxia represses HO-1 expression in three human cell types but induces it in rat, bovine, and monkey cells, indicating the inter-species difference in the hypoxic regulation of HO-1 expression. The hypoxia-mediated repression of HO-1 expression is consistently associated with the induction of Bach1, a heme-regulated transcriptional repressor, in human cells. Bach1 is a basic leucine zipper protein, forming a heterodimer with a small Maf protein. Expression of HO-1 was also reduced in human cells when exposed to interferon-gamma or an iron chelator desferrioxamine, each of which induced Bach1 expression. In contrast, induction of HO-1 expression by CoCl(2) is associated with reduced expression of Bach1 mRNA. Thus, expression of HO-1 and Bach1 is inversely regulated. We have identified a Maf recognition element in the human HO-1 gene that is required for repression of a reporter gene by hypoxia and targeted by Bach1. Therefore, Bach1 functions as a hypoxia-inducible repressor for the HO-1 gene, thereby contributing to fine-tuning of oxygen homeostasis in human cells.
Animals↗
Quality of life in obesity hypoventilation syndrome.
The first paper of this issue of Sleep and Breathing reports that the quality of life (QOL) assessed by the SF-36 and the Epworth Sleepiness Scale (ESS) in obesity hypoventilation syndrome (OHS) was compared with age- and body mass index-matched patients without hypoventilation (obese OSA), nonobese OSA patients, and healthy subjects. The QOL in OHS was worst among these four groups. After 3 to 6 months of nasal continuous positive airway pressure (CPAP) treatment, the QOL in OHS improved to the normal level similar to the two other OSA groups. We have observed severe nonobese OSA patients with hypoventilation. One of the risk factors, which related to a severe general condition, seems to be a small craniomandibular structure, which could induce an increase in upper airway resistance during sleep. Characteristics of Japanese OSA patients may be different from those in other countries. Although belatedly, the clinical study and management of sleep disordered breathing have just begun.
Body Mass Index↗
Nasal continuous positive airway pressure improves quality of life in obesity hypoventilation syndrome.
We studied the quality of life of obesity hypoventilation syndrome (OHS) by comparing it with age- and body mass index-matched patients without hypoventilation and age-matched obstructive sleep apnea (OSA) patients with body mass index (BMI) under 30, and the efficacy of nasal continuous positive airway pressure (CPAP) therapy for 3 to 6 months on the quality of life in these patients. Prospectively recruited patients from six sleep laboratories in Japan were administered assessments of the general health status by the Short-Form 36 Health Survey (SF-36) and subjective sleepiness by the Epworth Sleepiness Scale (ESS). Compared with matched healthy subjects, OHS and OSA patients not yet treated had worse results on the ESS scores and the SF-36 subscales for physical functioning, role limitations due to physical problems, general health perception, energy/vitality, role limitations due to emotional problems, and social functioning. The ESS scores of OHS patients were worse than those of the OSA groups including the age- and BMI-matched OSA patients. In the SF-36 subscales of OHS patients, only the subscale of social functioning showed worse results compared with that of BMI-matched OSA patients. After 3 to 6 months of treatment, ESS scores and these SF-36 subscales in all three patient groups improved to the normal level. These results suggested that the quality of life of OHS before nasal CPAP was significantly impaired and that nasal CPAP for OHS improved the quality of life associated with the improvement of daytime sleepiness to the level of the other OSA patients.
Adult↗
Effects of lung volume reduction surgery for emphysema on oxygen cost of breathing.
BACKGROUND: Patients with severe pulmonary emphysema have a greatly increased oxygen cost of breathing (O(2) cost), and this is the cause of serious malnutrition, or respiratory cachexia, in such patients. STUDY OBJECTIVES: To clarify the effect of lung volume reduction surgery (LVRS) on respiratory function and the nutritional state of these patients through a reduction in the O(2) cost of the respiratory muscles. DESIGN: Prospective cohort study. Setting, patients, and interventions: Twenty-three patients who underwent LVRS in Tohoku University Hospital. MEASUREMENTS: Pulmonary function and O(2) cost were measured perioperatively by utilizing a method of continuous dead space. In addition, we calculated the proportion of oxygen consumption (O(2)) of respiratory muscles to total O(2) (%O(2)resp) from the measured energy expenditure and the predicted values. RESULTS: FEV(1) and arterial oxygen pressure increased after surgery while lung volume and dyspnea decreased (p < 0.01), and O(2) cost was also reduced from 0.044 to 0.026 log(mL/min)/(L/min) [p < 0.001]. Moreover, the change in O(2) cost had a strong negative correlation with that of FEV(1) (r = - 0.70, p < 0.001), and a moderate positive correlation with that of the ratio of residual volume to total lung capacity (r = 0.54, p < 0.01). %O(2)resp was 23.1% at rest and 55.5% at maximal ventilation. LVRS reduced %O(2)resp at maximal ventilation to 49.0% (p < 0.05), but %O(2)resp at rest did not decrease after surgery. CONCLUSIONS: LVRS reduces energy expenditure of respiratory muscles especially during exercise by decreasing small airway obstruction and hyperinflated lung volume. This may reverse the malnourished state in end-stage emphysema.
Aged↗
Can nasal continuous positive airway pressure decrease clinic blood pressure in patients with obstructive sleep apnea?
Obstructive sleep apnea (OSA) is commonly associated with systemic hypertension and now recognized as an independent risk factor for daytime hypertension. We aimed to study the short- and long-term effect of nasal continuous positive airway pressure (CPAP) in hypertensive and normotensive patients with OSA. Forty-six patients with moderated to severe OSA were treated with nasal CPAP and followed after one year of treatment. Clinic blood pressure, heart rate, and body weight were taken before and followed up for one year after beginning nasal CPAP. In this study 25 patients with OSA were found to have hypertension (54.3%). The hypertensive group showed a significant reduction in clinic blood pressure after nasal CPAP, whereas the normotensive group showed no changes. The subgroup of hypertensive patients with OSA who had no anti-hypertensive medication revealed a decrease in clinic blood pressure comparable to those with anti-hypertensive drugs. The heart rate was not significantly changed in any patients. There was no significant correlation between the decrease in body weight and the reduction in blood pressure. These results suggest that nasal CPAP alone might have a substantial blood pressure lowering effect in hypertensive patients with OSA. This effect could decrease the morbidity and mortality related to cardiovascular complications in patients with OSA.
Adult↗
Pulmonary hypertension in patients with chronic obstructive pulmonary disease: recent advances in pathophysiology and management.
In patients with chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH) is associated with a worse prognosis. Recently, information has been increasing concerning the cellular and molecular aspects of the pathophysiology of PH in COPD. The most striking finding is the role of vascular endothelial cells and endogenous mediators released by these cells. Endothelial cell-dependent relaxation is impaired in COPD patients with PH. Moreover, vascular remodelling in these patients is mainly responsible for irreversible PH in advanced COPD. Smoking cessation will slow down the progression of the disease process and may prevent the development of PH in COPD. The timing of initiation of long-term oxygen therapy is important for the effective management of PH in COPD. Research on therapeutic agents for the effective treatment of PH is still needed in the management aspect of patients with COPD. This review focuses on the recent advances in our understanding of the pathophysiology and treatment of PH in COPD.
Cardiac Catheterization↗
Doxapram and perception of dyspnea.
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Adult↗