Hajime Kurosawa

Quantitative Assessment of the Pharyngeal Airway by Dynamic Magnetic Resonance Imaging in Obstructive Sleep Apnea Syndrome

Dynamic changes in the pharyngea airway of patients with obstructive sleep apnea syndrome (OSAS) were evaluated by quantitating the findings of real-time imaging performed during wakefulness and spontaneous sleep by means of dynamic magnetic resonance imaging (MRI). Six patients with OSAS and 3 non-OSAS subjects, selected prospectively and randomly, underwent polysomnography and dynamic MRI. The cross-sectional areas of the soft palate and oropharynx and the anterior-posterior airway dimensions seen during wakefulness and spontaneous sleep were calculated by US National Institutes of Health imaging software. On the basis of a case control study, comparisons were made with age-matched and body mass index—matched obese non-OSAS snorers. Spontaneous sleep caused significant obstruction and narrowing of various sites of the pharyngeal airway in the OSAS patients, but not in the non-OSAS subjects. During wakefulness, the non-OSAS subjects showed no marked narrowing of the pharyngeal airways, whereas a transient but significant narrowing was observed in the OSAS patients. The mean values of both the cross-sectional area and the anterior-posterior diameter at the soft palate were significantly reduced by spontaneous sleep in the OSAS patients. Dynamic MRI in awake OSAS patients shows promise as a routine diagnostic tool for localizing the upper airway collapse for appropriate selection of surgical therapy.

Renal protective effects of chronic exercise and antihypertensive therapy in hypertensive rats with chronic renal failure

Objectives Patients with chronic renal failure are restricted to mild physical activity and tend to a lack of exercise. However, there have been few reports regarding the influence of chronic exercise on the progression of renal disease. Similarly, there are few animal models concerned with the effect of exercise training on improving renal function. Therefore, we assessed the renal effects of moderate chronic treadmill exercise in a remnant kidney model of spontaneously hypertensive rats (SHR) with chronic renal failure. We also assessed the effects of exercise and antihypertensive therapy on renal function. Design and methods Eight-week-old SHR were subjected to 5/6 nephrectomy by removal of the left kidney and excision of two-thirds of the right kidney. The rats were divided into four groups: (i) no exercise (Non-EX); (ii) moderate exercise with treadmill running (20 m/min, 0 grade incline for 60 min) (EX); (iii) EX with an angiotensin converting enzyme (ACE) inhibitor, enalapril (2 mg/kg per day, i.p.); and (iv) EX with an angiotensin receptor antagonist, losartan (5 mg/kg per day, i.p.), for 4 weeks. Results Chronic EX significantly attenuated the increase in proteinuria (P < 0.01) and significantly protected against increases in the index of glomerular sclerosis (IGS). Both enalapril and losartan with EX significantly decreased blood pressure (P < 0.001), and further decreased the IGS. In the stepwise multiple regression analysis, only antihypertensive drug remained in the model as a significant predictor of IGS (P < 0.0001). In contrast, exercise, antihypertensive drug and mean systolic blood pressure (weeks 1–4) remained in the model as a significant predictors of mean proteinuria (weeks 1–4) (all P < 0.0001). Conclusions These results suggest that exercise does not worsen renal function and has renal-protective effects in this model of rats. Moreover, the antihypertensive therapy has additional renal-protective effects in this model of rats.

CO2 response for the brain stem artery blood flow velocity in man

We examined changes in the blood flow velocity of brain stem artery (BSA) and middle cerebral artery (MCA) in response to hypercapnic, normocapnic and hypocapnic hyperventilation in seven awake subjects with a transcranial Doppler to determine if there are differences in blood flow control in regional brain perfused by these respective arteries, and to separate the effects of CO2 and ventilation itself on blood flow velocity during CO2 loading. During hypercapnic hyperventilation, BSA flow velocity increased linearly with an increase in end-tidal partial pressure of CO2 (PETCO2). During hypocapnic hyperventilation, BSA flow velocity decreased linearly with decrease in PETCO2, but did not change during normocapnic hyperventilation. The mean CO2 reactivity of BSA was 2.8%/mmHg. The responses of MCA to these hyperventilations and CO2 reactivity were similar to those of BSA. These findings suggest that CO2 rather than ventilation per se is the important stimulus to changes in brain blood flow velocity and that the CO2 responses of brain arteries are not affected by differences in vascular beds.

Effects of exercise and β-blocker on blood pressure and baroreflexes in spontaneously hypertensive rats

Abstract Background Exercise training or β-blocker decreases high blood pressure (BP) and improves abnormal baroreflex function associated with hypertension. This study was undertaken to examine whether the effects of exercise training are additive to β-blocker in spontaneously hypertensive rats (SHR). Methods At 5 weeks of age, SHR were allocated to four groups: sedentary control, exercise training, treatment with moderate dose of bisoprolol, and their combination. Systolic BP was monitored by the tail-cuff method under restrained conditions. Sigmoidal mean arterial pressure (MAP)–heart rate (HR) reflex curves were obtained in rats at 17 weeks of age under quiet conditions before and after atenolol to ensure sympathetic blockade and to determine the vagal component of gain. After studying baroreflex function, intrinsic HR was obtained by additional administration of atropine. Results Before atenolol, both exercise training alone and bisoprolol alone lowered resting MAP and HR, and decreased upper plateau (maximal tachycardia) and lower plateau (maximal bradycardia), resulting in decreased sympathetic component of HR range (upper plateau − intrinsic HR) and increased vagal component of HR range (intrinsic HR − lower plateau). After atenolol, both exercise training alone and bisoprolol alone increased the gain of vagal component. Exercise training had no additive effect on any parameters to bisoprolol except for systolic BP and HR measured by the tail-cuff method. Conclusions Exercise training and bisoprolol have similar effects concerning resting hemodynamics and baroreflex function in SHR. Although additive effects of exercise training to bisoprolol are not evident under quiet, nonstressful conditions, some additive effects may be obtained under stress such as restrain.

Application of impulse oscillometry for within-breath analysis in patients with chronic obstructive pulmonary disease: pilot study

Background The impulse oscillometry is increasingly used for assessing the oscillatory mechanics of the respiratory system. The within-breath behaviour of the oscillatory mechanics in chronic obstructive pulmonary disease (COPD) is a well-known physiological feature. The purpose of this study was to develop a new approach for assessing this feature using impulse oscillometry. Methods The oscillatory mechanics were assessed by a commercially available impulse oscillometry device. The respiratory system resistance (Rrs) and reactance (Xrs) were measured during tidal breathing in patients with COPD (n=39) and healthy subjects (n=5). Selected data, the Rrs at 5 Hz (R5), Rrs at 20 Hz (R20), Xrs at 5 Hz (X5), and resonant frequency of Xrs (Fres) every 0.2 s, were extracted from the device. These data were divided into eight time fractions during the respiratory cycle to form averaged respiratory phases. Results The time courses of the R5 and X5 were notably dependent on the respiratory cycles in patients with COPD, while there was little such dependency in healthy subjects. Irrespective of respiratory phase, R5 and Fres increased, and X5 fell to a more negative level in patients with COPD in a severity-dependent fashion. The increase in the R5 and negative level in the X5 were more prominent in the middle of the expiratory phase. The severity dependence in the R20 was relatively small compared with that in the R5. Conclusions The results of this study suggest that impulse oscillometry can assess the within-breath behaviour of the oscillatory mechanics with high temporal resolution, which may be helpful for evaluating the severity of COPD. Further studies are needed to reveal which biomarkers obtained with this approach would be suitable for evaluating the airway obstruction.

Mesenchymal Stem Cells Correct Inappropriate Epithelial–mesenchyme Relation in Pulmonary Fibrosis Using Stanniocalcin-1

Current hypotheses suggest that aberrant wound healing has a critical role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). In these hypotheses, continuous TGF-β1 secretion by alveolar epithelial cells (AECs) in abnormal wound healing has a critical role in promoting fibroblast differentiation into myofibroblasts. Mesenchymal stem cells (MSCs) home to the injury site and reduce fibrosis by secreting multifunctional antifibrotic humoral factors in IPF. In this study, we show that MSCs can correct the inadequate-communication between epithelial and mesenchymal cells through STC1 (Stanniocalcin-1) secretion in a bleomycin-induced IPF model. Inhalation of recombinant STC1 shows the same effects as the injection of MSCs. Using STC1 plasmid, it was possible to enhance the ability of MSCs to ameliorate the fibrosis. MSCs secrete large amounts of STC1 in response to TGF-β1 in comparison to AECs and fibroblasts. The antifibrotic effects of STC1 include reducing oxidative stress, endoplasmic reticulum (ER) stress, and TGF-β1 production in AECs. The STC1 effects can be controlled by blocking uncoupling protein 2 (UCP2) and the secretion is affected by the PI3/AKT/mTORC1 inhibitors. Our findings suggest that STC1 tends to correct the inappropriate epithelial-mesenchymal relationships and that STC1 plasmid transfected to MSCs or STC1 inhalation could become promising treatments for IPF.

Effects of angiotensin-converting enzyme inhibitor and exercise training on exercise capacity and skeletal muscle.

Objective Physical fitness is closely related with cardiovascular health. We examined the effects of angiotensin-converting enzyme inhibitor, exercise training and their combination on exercise capacity as well as skeletal muscle fiber type and capillarity in spontaneously hypertensive rats (SHR). Methods Seven-week-old male SHR were allocated to four groups: sedentary control (C), treatment with perindopril (3 mg/kg per day) (Per), exercise training on a treadmill (EX), and their combination (Per + EX). Following 8-week interventions, rats were submitted to a stepwise exercise test on a treadmill. After experiments, fiber type and capillarity in soleus muscle were examined. Results Exercise capacity significantly increased in Per compared with in C. Combination of exercise training and perindopril further increased exercise capacity compared with perindopril alone, whereas there was no significant difference in exercise capacity between EX and Per + EX. Capillary density increased similarly in Per and EX compared with in C. Combination of exercise training and perindopril further increased capillary density compared with exercise training alone. The percentage of type I fiber increased only in Per + EX. Conclusions We found that in growing SHR, chronic treatment with perindopril enhances untrained exercise capacity, while it does not affect acquired exercise capacity as a result of exercise training. We also found that perindopril promotes adaptive changes of skeletal muscle in response to exercise such as increases in capillary density and percentage of type I fiber.

Clinical Application of the Forced Oscillation Technique

The forced oscillation technique (FOT) is a noninvasive method with which to measure respiratory system resistance and reactance during tidal breathing. Recently, its clinical application has spread worldwide with the expansion of commercially available broadband frequency FOT devices, including MostGraph and Impulse Oscillometry. An increasing number of reports have supported the usefulness of the FOT in the management of asthma and chronic obstructive pulmonary disease (COPD). However, the FOT is not a surrogate test for spirometry, but should be used complementarily. Furthermore, reference values are not necessarily available and the interpretation of some measured data is controversial. There is a need to update the international statement for not only technical aspects but also the clinical use of the FOT. In this review, we summarize the previously published studies and discuss how to use the FOT in a clinical setting.

Effects of Estradiol, Angiotensin-Converting Enzyme Inhibitor and Exercise Training on Exercise Capacity and Skeletal Muscle in Old Female Rats

Physical fitness is closely related to cardiovascular health. We examined the effects of estradiol, angiotensin-converting enzyme inhibitor, exercise training, and their combination on exercise capacity as well as skeletal muscle fiber type and capillarity in old female rats. Twelve-month-old female Wistar-Kyoto rats were allocated to six groups: control (C), treatment with 17 beta-estradiol (0.025 mg/kg/dose, i.p. twice a week) (Est), perindopril (2 mg/kg/day) (Per), exercise training on a treadmill (15 m/min, 10 grade incline, 60 min/day, 5 days/week) (Exe), and combinations of a drug and exercise training (Exe+Est and Exe+Per). Following 6-month interventions, the rats were submitted to a stepwise exercise test on a treadmill. Moreover, fiber type and capillarity in both the soleus and gastrocnemius muscles were examined. Exercise capacity, capillary density, and the percentage of type I fiber significantly increased in Exe, Exe+Est, and Exe+Per compared to C. There were no significant differences in exercise capacity, capillary density, and percentage of type I fiber among C, Est, and Per. The combination of exercise training and perindopril further increased capillary density in both the soleus and gastrocnemius muscles, and the percentage of type I fiber in the gastrocnemius muscle compared to exercise training alone. We found that in old female rats, chronic treatment with estradiol or perindopril affected neither untrained exercise capacity nor exercise capacity acquired as a result of exercise training. However, we found that perindopril promotes adaptive changes of skeletal muscle in response to exercise such as increases in capillary density and the percentage of type I fiber.

Understanding the oldest old in northern Japan: An overview of the functional ability and characteristics of centenarians

Aim:  To increase knowledge of the functional ability of centenarians by examining the situation of Japanese centenarians residing in an urban region in northern Japan.