Physiological gas exchange in the middle ear cavity

Hamada, Y.; Utahashi, Hiroya; Aoki, Kazuhiro

doi:10.1016/s0165-5876(02)00040-x

Cited by 22 publications

(23 citation statements)

References 18 publications

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“…(17). It has been determined that gas exchange can occur both into and out of the middle ear cavity via the eustachian tube and also by passive diffusion across the middle ear mucosa (22,53). Furthermore, the chinchilla eustachian tube appears to be continually semipatulous where a constant airflow may be maintained by the passage of air into the middle ear cleft (15).…”

Section: Discussionmentioning

confidence: 99%

A Mutation in the sap Operon Attenuates Survival of Nontypeable Haemophilus influenzae in a Chinchilla Model of Otitis Media

2005

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Bacteria have evolved strategies to resist killing by antimicrobial peptides (APs), important effectors of innate immunity. The sap (sensitivity to antimicrobial peptides) operon confers resistance to AP-mediated killing of Salmonella. We have recently shown that sapA gene expression is upregulated in the middle ear in a chinchilla model of nontypeable Haemophilus influenzae (NTHI)-induced otitis media. Based on these findings, we constructed an NTHI strain containing a Lux reporter plasmid driven by the sapA promoter and demonstrated early yet transient expression of the sap operon within sites of the chinchilla upper airway upon infection. We hypothesized that the sap operon products mediate NTHI resistance to APs. In order to test this hypothesis, we constructed a nonpolar mutation in the sapA gene of NTHI strain 86-028NP, a low-passagenumber clinical isolate. The sapA mutant was approximately eightfold more sensitive than the parent strain to killing by recombinant chinchilla ␤-defensin 1. We then assessed the ability of this mutant to both colonize and cause otitis media in chinchillas. The sapA mutant was significantly attenuated compared to the parent strain in its ability to survive in both the nasopharynx and the middle ear of the chinchilla. In addition, the mutant was impaired in its ability to compete with the parent strain in a dual-strain challenge model of infection. Our results indicate that the products of the sap operon are important for resisting the activity of APs and may regulate, in part, the balance between normal carriage and disease caused by NTHI.

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Section: Discussionmentioning

confidence: 99%

A Mutation in the sap Operon Attenuates Survival of Nontypeable Haemophilus influenzae in a Chinchilla Model of Otitis Media

2005

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“…This assumption was further supported experimentally in rabbits where phase Ba^did not occur when the ME was initially flushed with a gas mixture containing 5% CO 2 (similar to venous blood; Hamada et al 2002).…”

Section: Introductionmentioning

confidence: 84%

“…Data obtained from phase Ba^(Figs. 4, 5, and 6) were used for the analysis under the previously supported assumption that the initial volume increase in that phase represents diffusion of CO 2 from the blood into the air-flushed ME, down its partial pressures difference (Hamada et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Whereas some (e.g., humans, guinea pigs, pigs) have complex gas-filled systems containing multiple connected cells (e.g., the mastoid gas cell system in humans) that are connected to the ME cavity itself, others (e.g., rats, rabbits) have a rather simple structure (bulla) (Hellströ m et al 1982;Judkins and Li 1997;Goksu et al 1992;Pracy et al 1998;Hamada et al 2002).…”

Section: Introductionmentioning

confidence: 99%

“…In this way, the normal steady-state condition of ME gas is challenged, and until steady state is reestablished, the general gas exchange process over time can be studied. This general method has been used in different animals, e.g., rabbits (Hamada et al 2002), rats (Kania et al 2004), and monkeys (Doyle and Seroky 1994;Doyle et al 1995, and also in humans (Aoki et al 1998;Uchimizu et al 2005). It has also been described by mathematical models (e.g., Fink et al 2003).…”

Section: Introductionmentioning

confidence: 99%

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High-Resolution Measurements of Middle Ear Gas Volume Changes in the Rabbit Enables Estimation of its Mucosal CO2 Conductance

Marcusohn

Dirckx

2006

JARO

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Transmucosal CO(2) exchange in the middle ear (ME) of the New Zealand White rabbit (Oryctolagus cuniculus) was studied using an accurate novel detecting and recording system for measuring gas volume changes at constant pressure, based on a principle that was previously used by Kania et al. (Acta Otolaryngol 124:408-410, 2004). After the ME cavity was washed with ambient air, the initial diffusion rate of CO(2) (V(.-)(i)CO(2)) from the blood perfusing the ME mucosa was calculated from gas volume change measurements. In nine cases, the (V(.-)(i)CO(2))calculated after normalization due to shifts in baseline was 314+/-112 microL x h(-1) (mean +/- SD). In two cases where normalization was not needed, (V(.-)(i)CO(2)) was 409 microL x h(-1) (276 and 543 microL x h(-1)). Normalization of (V(.-)(i)CO(2)) data was also made in five additional cases where secretion of fluids from the lining of the ear canal was observed. In these cases (V(.-)(i)CO(2)) was 245 +/- 142 microL x h(-1). No differences were found between results obtained in the three groups. Thus, an overall mean value of (V(.-)(i)CO(2)) of 305 +/- 131 microL x h(-1) (n = 16) was calculated. An effective coefficient of conductance of CO(2) (G(CO(2))) between the mucosal circulation and the ME gas cavity of the New Zealand White rabbit was estimated to be approximately 0.05 microL (h x Pa)(-1) and compared to the G(CO(2)) estimated for humans in a different study.

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Myringotomy in the Junbo mouse model of chronic otitis media alleviates inflammation and cellular hypoxia

2014

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Objectives/Hypothesis: Ventilation of the chronically inflamed middle ear is a key outcome in functional middle ear surgery. Grommets eliminate middle ear effusion, but there is also evidence that they downregulate inflammation. The reason for this is not understood, but there is little to suggest alteration in eustachian tube ventilatory capacity. Previous work has shown that the Junbo mouse model of chronic otitis media has hypoxic middle ear mucosa and bulla fluid leucocytes. Here we explore whether surgical ventilation may alleviate chronic otitis media through downregulation of hypoxia.Study Design: Surgical intervention on a mouse model of disease. Methods: We established patency of myringotomy incision as 5 days in wild-type mice. We performed unilateral myringotomy on three cohorts of mice: 10 wild-type controls, 12 Junbo mice, and 15 Junbo mice with additional removal of middle ear effusion. A small cohort of these mice were labeled in vivo by intraperitoneal injection of pimonidazole to identify tissue hypoxia. Tissues were assessed for mucoperiosteal thickening and pimonidazole labeling, comparing operated to nonoperated ears.Results: Ventilation of the inflamed Junbo middle ear revealed significant reduction in inflammatory thickening associated with loss of pimonidazole labeling, suggesting resolution of cellular hypoxia.Conclusions: Surgical ventilation may achieve therapeutic effect through alleviation of cellular hypoxia in the chronically inflamed middle ear. Targeted molecular therapy of hypoxia signaling may offer future alternative therapy for chronic otitis media.

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Physiological gas exchange in the middle ear cavity

Cited by 22 publications

References 18 publications

A Mutation in the sap Operon Attenuates Survival of Nontypeable Haemophilus influenzae in a Chinchilla Model of Otitis Media

A Mutation in the sap Operon Attenuates Survival of Nontypeable Haemophilus influenzae in a Chinchilla Model of Otitis Media

High-Resolution Measurements of Middle Ear Gas Volume Changes in the Rabbit Enables Estimation of its Mucosal CO2 Conductance

Myringotomy in the Junbo mouse model of chronic otitis media alleviates inflammation and cellular hypoxia

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