Ear Perfusion Research Articles

Pneumatic external counterpulsation (PECP): a new treatment option in therapy refractory inner ear disorders?

The established therapeutic principle for sudden deafness and tinnitus is based on the stimulation of the inner ear perfusion by infusion therapy using vaso-active or hemodilutive agents. Concerning a mechanically induced increase of the inner ear's blood supply, the new technique of Pneumatic External Counterpulsation (PECP) was performed. This technique had already been used successfully in patients suffering from coronary heart disease. Due to an ECG-guided pneumatic compression of the lower extremities during diastole an increase of arterial perfusion of the extracranial supplying brain vessels can be obtained by PECP-treatment. PECP was used in 33 patients (22 males, 11 females) between 19 and 76 years of age suffering from persisting acute hearing disorders and/or tinnitus after adequate infusion therapy. 3 patients revealed mild complications during PECP-treatment (e.g. thoracic pain) which seemed to be related to the therapeutic regime and disappeared completely after cessation of PECP. 30 patients underwent PECP-treatment on 5 following days for 1 hour. This standardized hourly treatment regime was extended to 10 days in 12 patients. Therapeutic effects were determined by color-coded duplexsonography and pure tone audiometry eventually masking the audiogram. During treatment an increase of 19% flow volume in the internal carotid arteries and of 11% in the vertebral arteries was evaluated using color-coded duplexsonography. In 47% of cases (n = 14) decrease of tinnitus intensity and/or tinnitus appearance with an average of 16 dB was perceived after the end of the treatment series. Hearing threshold increased in 28% of cases (n = 7) with an average threshold shift of 19 dB after PECP-treatment. All patients were examined by pure tone audiometry during the follow-up after 4, 8 and 12 weeks as well as after 6 and 12 months. In all cases the audiometric benefit lasted throughout the follow-up 1 year, after treatment. The determination of a positive correlation between vascular flow increase in the extracranial brain-supplying vessels during PECP-treatment and the encouraging therapeutic results obtained by audiometry seem to make this new and promising therapeutic option effective, practicable and easy to handle. These preliminary results of the PECP technique should be validated in further studies featuring larger numbers of patients suffering from therapy-resistant inner ear disorders.

Ibuprofen modulates tissue perfusion in partial-thickness burns

Introduction. The anti-inflammatory and anticoagulant effects of ibuprofen and heparin may enhance skin perfusion in cutaneous scald burns. To test this hypothesis, skin perfusion and edema formation in scald burned rabbit ears were measured. Method. Eighteen rabbits (3.5–4.5 kg) received partial-thickness scald burns to one ear and then were given normal saline, n=6, 20 mg/kg ibuprofen, n=6, or 700 IU/kg heparin, n=6. Skin perfusion, blood flow and edema formation in the burned ear were measured with laser Doppler, ultrasound flowmeter and skin calipers, respectively. Statistical analysis was performed using repeated measures ANOVA with post hoc Scheffe's test for comparison between groups. Results. Blood flow to the scald burned ear increased 10–15 times that of baseline with tissue perfusion increasing by 70% within 0.5 h compared to pre-burn. Ibuprofen maintained the elevated tissue perfusion for 5 h while the heparin and saline groups showed decreases to 95 and 35% of pre-burn values, respectively. The heparin and ibuprofen groups demonstrated significant increases in ear perfusion at 4 and 5 h postburn. Ibuprofen also showed a significant difference within the first hour postburn, p<0.01. Wet to dry weight ratios in burned ear tissue were greater in rabbits receiving saline or heparin compared to ibuprofen at 3.6±0.2 and 2.9±0.3 vs. 2.1±0.1, respectively ( p<0.001). Conclusion. Ibuprofen increases tissue perfusion and reduces edema formation in scald burned rabbit ears.

Effects of Morphine in Decomposing Bodies on the Development of Lucilia sericata (Diptera: Calliphoridae)

This study concerns the effects of morphine in tissues on the rate of development of Lucilia sericata (Diptera: Calliphoridae) using those tissues as a food source. Lucilia sericata is a species of fly commonly found on human corpses in Europe during the early stages of decomposition and thus of forensic interest. Three rabbits were administered 12.5, 25.0 and 50.0 mg/h of morphine chlorhydrate via ear perfusion over a period of 3 h. These dosages and duration of perfusion were calculated to give tissue concentrations of morphine similar to those encountered in fatal human overdoses. A fourth rabbit was used as a control. Following administration of the drug, rabbits were sacrificed and 400 eggs of Lucilia sericata, all of the same age, were placed in the eyes, nostrils and mouth of each rabbit. Developing larvae were sampled daily to determine growth rate and weight. Puparia and emerging adult flies were also sampled. Data were analyzed using analysis of variance (ANOVA) and Student's T-test. Results of this study show that an underestimation of the postmortem interval of 24 h is possible if the presence of morphine in tissues is not considered. This study demonstrates again the necessity of considering the possible effects of drugs in tissues on insect growth rates when estimating the postmortem interval using entomological techniques.

Cytokine and Chemokine Induction Using Cell Wall Component and Toxin Derived from Gram-Positive Bacteria in the Rat Middle Ear

Lipoteichoic acid (LTA) is one of the components present within the cell wall layer of most gram-positive bacteria. It plays an important role in the initiation and progression of bacterial infection. In this study, we performed a rat middle ear and nasal perfusion with LTA purified from two different gram-positive bacterial species. Using ELISA and RT-PCR, the production and mRNA expression of rat chemokine, GRO/CINC-1, proinflammatory cytokine, TNF-alpha, in rat middle ear lavage and mucosa were investigated. GRO/CINC-1 in middle ear lavage was produced by stimulation of LTA in a time-dependent fashion; however, TNF-alpha production into the lavage was not detectable using ELISA assay. The mRNA expressions of GRO/CINC-1 and TNF-alpha in the middle ear mucosa were both induced after LTA and exotoxin exposures. The expression of IL-10 mRNA was also induced after 6 h of LTA and exotoxin exposures. The profile of the production of GRO/CINC-1 and TNF-alpha in rat nasal lavage was similar to that in the middle ear; however, the mRNA expressions of GRO/CINC-1, TNF-alpha and IL-10 in the nasal mucosa were different from those in the middle ear mucosa. These results suggest that the cell wall component and exotoxin of gram-positive bacteria can induce several cytokines in vivo and play an important role in the initiation of the inflammatory cascade in the middle ear.

Role of allergy in eustachian tube blockage and otitis media with effusion: A review

Recent studies continue to support a role for allergy in the pathogenesis of otitis media with effusion. Although a variety of mechanisms have been proposed to relate these two disease conditions causally, none has been completely validated by experimental or clinical studies. This review suggests that the observed relationship between allergy and otitis media with effusion is caused by mediators of inflammation and cytokines and colony-stimulating factors released by mucosal mast cells and other inflammatory and epithelial cells in the nose and nasopharynx. These mediators produce blockage of the eustachian tube through a number of mechanisms, which may include local injury or vascular- or neural-mediated changes in the eustachian tube opening pressure and in middle ear perfusion. It is likely that the nasal allergic response in patients predisposes to eustachian tube blockage and, if prolonged, causes changes in gas absorption in the middle ear space. This gas exchange primarily involves nitrogen absorption, which may take several days to develop. This persistent underpressure will then lead to middle ear effusion. Irrespective of the theoretical mechanism, the relationship between allergy and otitis media with effusion will remain controversial until well-controlled clinical studies are conducted documenting that in select populations antiallergy therapy is efficacious in preventing or limiting the duration of otitis media with effusion. (Otolaryngol Head Neck Surg 1996;114:562-8.)

Role of Allergy in Eustachian Tube Blockage and Otitis Media with Effusion: A Review

Recent studies continue to support a role for allergy in the pathogenesis of otitis media with effusion. Although a variety of mechanisms have been proposed to relate these two disease conditions causally, none has been completely validated by experimental or clinical studies. This review suggests that the observed relationship between allergy and otitis media with effusion is caused by mediators of inflammation and cytokines and colony-stimulating factors released by mucosal mast cells and other inflammatory and epithelial cells in the nose and nasopharynx. These mediators produce blockage of the eustachian tube through a number of mechanisms, which may include local injury or vascular- or neural-mediated changes in the eustachian tube opening pressure and in middle ear perfusion. It is likely that the nasal allergic response in patients predisposes to eustachian tube blockage and, if prolonged, causes changes in gas absorption in the middle ear space. This gas exchange primarily involves nitrogen absorption, which may take several days to develop. This persistent underpressure will then lead to middle ear effusion. Irrespective of the theoretical mechanism, the relationship between allergy and otitis media with effusion will remain controversial until well-controlled clinical studies are conducted documenting that in select populations antiallergy therapy is efficacious in preventing or limiting the duration of otitis media with effusion.

Absorption and metabolism of hydrocortisone 21-butyrate, 21-hemisuccinate and hydrocortisone by skin of the rabbit ear during single-pass perfusion.

1. Rabbit ear was single-pass perfused with protein-free buffer solution at a rate of 0.02 ml/min per cm2 surface area for up to 6 h. 2. Hydrocortisone or hydrocortisone 21-butyrate or hydrocortisone 21-hemisuccinate was applied dermally (0.01-1.0% w/w) in suspension with isopropyl myristate or dissolved in 1,2-propanediol. The ointments were stiffened with 5% polyethylene 1500 or 1.2% methylcellulose respectively. 3. Hydrocortisone was slowly absorbed and did not reach a steady-state absorption rate during the experimental period. 4. No metabolites of hydrocortisone were found during ear perfusion. In the supernatant of skin homogenate, however, cortisone, hydrocortisone-20 alpha-ol and another, as yet unidentified metabolite, were observed. 5. Hydrocortisone 21-butyrate was completely hydrolysed during dermal absorption, showing steady-state concentrations of hydrocortisone in the effluent. Hydrocortisone 21-hemisuccinate did not reach steady-state concentrations in the effluent. About two-thirds was hydrolysed during absorption. 6. During arterial perfusion approximately 30% of hydrocortisone 21-butyrate was hydrolysed whereas 97% of hydrocortisone 21-hemisuccinate remained intact. 7. First-pass ester hydrolysis in skin may be complete for the poorly absorbed glucocorticoids leading to metabolites of less lipophilicity.

Ester hydrolysis and conjugation reactions in intact skin and skin homogenate, and by liver esterase of rabbits.

1. Procaine, 2-chloroprocaine, ethyl aminobenzoate and methyl salicylate were added at various concentrations to liver esterase, supernatant of skin homogenate, or single-pass perfused ears of rabbits. 2. Vmax of product formation by purified liver esterase correlated with the rank order of the distribution coefficients (n-octanol/buffer) of the substrates and ranged between 11 and 1100 pmol/min per micrograms protein. Km values were between 20 and 50 microM. 3. No correlation was observed when the apparent enzyme kinetics, calculated by non-linear adaptation, were compared with each other after substrate administration to skin, arterial influx, or incubation with skin homogenate. 4. An acid labile conjugate of ethyl 4-aminobenzoate was found, mainly during arterial perfusion and in supernatant of skin homogenate, after administration of ethyl 4-aminobenzoate. 5. Acetamidobenzoic acid was observed in quantities of about 10% of the free 4-aminobenzoic acid during dermal or arterial application of procaine. This metabolite was not found with ethyl 4-aminobenzoate. 6. The results from isolated rabbit ear perfusion differ quantitatively and qualitatively with those obtained from supernatant of skin homogenate or purified liver esterase.

Clinical Experience with Early Post-mortem Human Inner Ear Perfusion

Early fixation of human temporal bones is a difficult but very important task. The author reports on his experience in hospital wards.

T-2 toxin can cause vasoconstriction in an in vitro bovine ear perfusion system

An in vitro bovine ear perfusion system was used to examine the effect of T-2 toxin on peripheral vasculature. T-2 toxin caused a dose-related increase in the perfusion pressure, with an apparent threshold concentration of 1 × 10 −5 m. The effect of the toxin was observed irrespective of the presence of either histamine or norepinephrine in the system. The presence of known histaminic or noradrenergic antagonists did not affect the response to the toxin. Once the vessel was exposed to T-2 toxin, the response to histamine or norepinephrine was decreased.

Effect of pentoxifylline ('Trental') on cochlear blood flow as measured by hydrogen wash-out.

A comparative experimental study was carried out in guinea-pigs to assess the effect of pentoxifylline on inner ear perfusion. Five animals were given a single dose of 30 mg pentoxifylline per 10-minute intravenous infusion and the cochlear blood flow measured by means of the hydrogen-clearance technique before and after administration of the drug. A control group of 11 animals received the solvent only. Compared to controls, a significant increase in inner ear blood flow was observed in the pentoxifylline-treated animals. These data may explain positive clinical findings with pentoxifylline in otological disorders associated with impaired cochlear perfusion.

Effects of hypoxia and acidosis on vascular plasminogen activator release in the pig ear perfusion system

The influence of hypoxia and acidosis on the release of vascular plasminogen activator was studied in the isolated perfused pig ear. Perfusion with deoxygenated or acid solutions led to significant increases in plasminogen activator release (p<0.001); acid solutions of pH 6.7 were more effective than those of pH 6.9. Perfusions with lactate and AMP, two metabolic products which might act as mediators of fibrinolytic stimulation during hypoxia, resulted in moderate increases of plasminogen activator in the effluent p<0.01).

Early Vasoconstriction Induced in the Isolated Rabbit's Ear by X-Radiation

lowed flow measurements at 5-minute intervals only and made it necessary to interrupt perfusion during irradiation; therefore onset and time course of the vascular reaction could not be established. In the present study, determination of these factors was accomplished with an improved technique that permitted both ear perfusion as well as flow rate recording to be performed continuously. Furthermore, the protein washout found previously with a half-quantitative method was re-examined with a much more sensitive and accurate technique. METHOD