Yasuyoshi Ohshima

Impaired ventilation and metabolism response to hypoxia in histamine H1 receptor-knockout mice.

The role of central histamine in the hypoxic ventilatory response was examined in conscious wild-type (WT) and histamine type1 receptor-knockout (H1RKO) mice. Hypoxic gas (7% O(2) and 3% CO(2) in N(2)) exposure initially increased and then decreased ventilation, referred to as hypoxic ventilatory decline (HVD). The initial increase in ventilation did not differ between genotypes. However, H1RKO mice showed a blunted HVD, in which mean inspiratory flow was greater than that in WT mice. O(2) consumption (V(O2)) and CO(2) excretion were reduced 10min after hypoxic gas exposure in both genotypes, but (V(O2)) was greater in H1RKO mice than in WT mice. The ratio of minute ventilation to (V(O2)) during HVD did not differ between genotypes, indicating that ventilation is adequately controlled according to metabolic demand in both mice. Peripheral chemoreceptor sensitivity did not differ between genotypes. We conclude that central histamine contributes via the H1 receptor to changes in metabolic rate during hypoxia to increase HVD in conscious mice.

Effects of fasting on hypoxic ventilatory responses and the contribution of histamine H1 receptors in mice

We tested the hypothesis that fasting affects hypoxic ventilatory responses through metabolic changes via histamine H1 receptors. Wild-type (WT) and histamine H1 receptor knockout (H1RKO) mice were studied in fed and fasted states. In the fed WT, hypoxic-gas exposure elicited an increase and a subsequent decline in ventilation (hypoxic ventilatory decline or HVD). HVD was influenced by fasting in breathing pattern with metabolic rate. Fasting elicited hypoglycemia, a drop in R, and increases in free fatty acid and ketone bodies in the serum. In H1RKO, HVD was blunted in the fed state, but it appeared in the fasted state. There was a minimal drop in R following fasting and a low triglyceride concentration. Thus, fasting affects HVD through a change in energy mobilization from glucose to lipid metabolism. Histamine H1 receptors are involved in HVD during fed and fasted states, resulting in adaptation to the environmental conditions.

Circadian Changes in Respiratory Responses to Acute Hypoxia and Histamine H1 Receptors in Mice

Central histamine has crucial roles in circadian rhythm, ventilation, and the balance of energy metabolism via H1 receptors. We focused on the variation in ventilatory responses to hypoxia between light and dark periods, and the requirement of histamine H1 receptors for the circadian variation, using wild-type (WT) and histamine H1 receptor-knockout (H1RKO) mice. In WT mice, minute ventilation (V(E)) during hypoxia was higher in the dark period than in the light period. In H1RKO mice, changes in V(E) between photoperiods were minimal because V(E) increased relative to VO(2) (particularly in the light period). H1RKO mice showed metabolic acidosis, and increased levels of ketone bodies in blood during the light period. These data suggested that changes in V(E) during hypoxia vary between light and dark periods, and that H1 receptors have a role in the circadian variation in V(E) through control of acid-base status and metabolism in mice.

Effect of thixotropy conditioning of inspiratory muscles on the chest wall response to CPAP

Background and objective:  Thixotropy conditioning of inspiratory muscles changes the end‐expiratory position of the respiratory system during resting breathing. We examined the immediate effects of thixotropy conditioning of inspiratory muscles on chest wall inflation induced by CPAP.

Breathing Irregularity Is Independently Associated With the Severity of Obstructive Sleep Apnea in Patients With Multiple System Atrophy

STUDY OBJECTIVES Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the combination of cerebellar ataxia, parkinsonism, and autonomic disturbance. Patients with MSA frequently have sleep-disordered breathing. In some patients with MSA, central sleep apnea manifests during the diseases natural course or as a treatment effect. Breathing instability may be involved in the development of obstructive sleep apnea (OSA); therefore, we investigated whether breathing instability affects the severity of OSA in patients with MSA. METHODS Patients with MSA and a control group of individuals who were matched for age, body mass index (BMI), and supine apnea-hypopnea index (AHI) were recruited. Breathing instability was evaluated by using polysomnography to determine the irregular pattern with approximate entropy (ApEn) of chest respiratory movements during wakefulness before sleep onset. The ApEn values were compared between the groups. The severity of OSA was evaluated with background parameters and ApEn values by regression analysis. RESULTS Twenty patients with MSA (9 men; mean age, 61 years; BMI, 24.1 kg/m2; supine AHI, 37.9 events/h) were compared to the control group. The ApEn values were higher in the patients with MSA than those in the control group (1.28 versus 1.11; P < .05). Multiple regression analysis showed that supine AHI was associated with ApEn values but not with BMI in patients with MSA and associated with BMI but not with ApEn values in the individuals in the control group. CONCLUSIONS Patients with MSA had more breathing irregularity. In patients with MSA, breathing instability may be a more influential factor for OSA than BMI. COMMENTARY A commentary on this article appears in this issue on page 1641.

Time-Dependent Ventilatory Response to Poikilocapnic Hypoxia during Light and Dark Periods and the Role of Histamine H1 Receptors in Mice

We tested the hypothesis that the biphasic ventilatory response to poikilocapnic hypoxia shows circadian variation and contribution of histamine H1 receptors in mice. Initial increases in ventilation were augmented during dark periods. H1 receptors had no major relationship with circadian variation, but affected the declined phase.