Software toolbox for analysis of the endometrial myometrial junction - a pilot study.

PURPOSE: To develop and evaluate an algorithm for computerized evaluation and measurement of the endometrial-myometrial junction (EMJ). MATERIALS AND METHODS: The advanced image processing toolbox of the Matlab software package was used for identificiation and quantitative analysis of the EMJ area on three-dimensional (3D) rendered coronal plane uterine images, with clear-cut borders of the EMJ. The algorithm was used to process the images and calculate the geometric parameters characterizing the identified EM The manual measurements of the maximum thickness of the EMJ were compared to automated measurements performed by the algorithm on the same images. RESULTS: For all three interfaces, the mean maximum manual measurement was less than the mean maximui computed measurement. The differences between the two measurements were not statistically significant (p = 0.275, 0.608 and 0.41 for the right wall, left wall, and fundus, respectively). The mean systematic and random errors ranged from 5.4% tol9.3% and 20.4 to 48.6%, respectively. Pearson correlations for the right wall, left wall and fundus (r = 0.642, p = 0.001; r = 0.730, p < 0.001, and r 0.694, p < 0.001, respectively) were good. CONCLUSIONS: Maximum EMJ thickness measurements performed by the innovative Matla software algorithm are as accurate as manual measurements, and have the potential to reduce inter-observer variability.

Prediction of microcephaly at birth using three reference ranges for fetal head circumference: can we improve prenatal diagnosis?

OBJECTIVE: To evaluate the prediction of microcephaly at birth (micB) using established and two new reference ranges for fetal head circumference (HC) and to assess whether integrating additional parameters can improve prediction. METHODS: Microcephaly in utero was defined as a fetal HC 3SD below the mean for gestational age according to Jeanty et al.'s reference range. The records of cases with fetal microcephaly (Fmic) were evaluated for medical history, imaging findings, biometry and postnatal examination/autopsy findings. Microcephaly was confirmed at birth (micB) by an occipitofrontal circumference (OFC) or a brain weight at autopsy 2SD below the mean for gestational age. The new INTERGROWTH-21(st) Project and a recent Israeli reference for fetal growth were applied for evaluation of the Fmic positive predictive value (PPV) for diagnosis of micB cases. Optimal HC cut-offs were determined for each of the new references with the aim of detecting all micB cases whilst minimizing the number of false positives found to have a normal HC at birth. We also assessed the difference between the Z-scores of the prenatal HC and the corresponding OFC at birth, the frequency of small-for-gestational age (SGA), decreased HC/abdominal circumference (AC) and HC/femur length (FL) ratios, the prevalence of associated malformations and family history. RESULTS: Forty-two fetuses were diagnosed as having Fmic according to the Jeanty reference, but micB was confirmed in only 24 (PPV, 57.1%). The optimal INTERGROWTH and Israeli reference HC cut-offs for micB diagnosis were mean - 3SD and mean - 2.3SD, resulting in a statistically non-significant improvement in PPV to 61.5% and 66.7%, respectively. The presence of a family history of microcephaly, SGA, associated malformations and application of stricter HC cut-offs resulted in a higher PPV of micB, although not statistically significant and with a concurrent increase in the number of false-negative results. The deviation of the HC from the mean, by all references, was significantly larger compared with the actual deviation of the OFC at birth, with mean differences between the corresponding Z-scores of -1.15, -1.95 and -0.74 for the Jeanty, INTERGROWTH and Israeli references, respectively. CONCLUSIONS: The evaluated reference ranges all result in considerable over-diagnosis of fetal microcephaly. The use of the two new HC reference ranges did not significantly improve micB prediction compared with that of Jeanty et al., whilst use of additional characteristics and stricter HC cut-offs could improve the PPV with an increase in false negatives. The postnatal OFC deviates significantly less from the mean compared with the prenatal HC, and we propose that adjustment for this would enable better prediction of the actual OFC deviation at birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Increased mechanical strain imposed on murine lungs during ventilation in vivo depresses airway responsiveness and activation of protein kinase Akt.

Continuous positive airway pressure (CPAP) administered to tracheostomized rabbits and ferrets for 4 days or 2 wk suppresses bronchial reactivity in vivo and suppresses airway reactivity in lobes and tracheal segments isolated from these animals. In vitro studies of canine tracheal smooth muscle tissues indicate that mechanical loading suppresses the activation of the growth regulatory kinase, Akt, and that Akt is a negative regulator of smooth muscle differentiation. The transduction of mechanical signals in the tracheal tissues in vitro is mediated by integrin-associated adhesion complexes. To determine whether airway responsiveness and Akt activation are modulated by mechanical loads applied for short time periods to the airways of living animals in vivo, mice were mechanically ventilated for 2 h with high (5 cmH2O) or low (0-1 cmH2O) positive end-expiratory pressure (PEEP) and then ventilated at low PEEP for 30 min. Ventilation of mice with PEEP in vivo for 2 h depressed airway responsiveness to methacholine measured in vivo subsequent to the PEEP treatment. Airway narrowing in vitro in intraparenchymal airways in isolated lung slices and contractile responses of isolated tracheal segments in vitro were suppressed for at least 6 h subsequent to the in vivo exposure to PEEP. Tracheal segments isolated from high PEEP-treated mice exhibited significantly lower levels of Akt activation than tracheae from low PEEP-treated mice. The results indicate that mechanical loads imposed in vivo result in physiological and biochemical changes in the airway tissues after a relatively short 2-h period of in vivo loading.

Sonographic imaging of fetal tympanic rings.

OBJECTIVE: To examine the feasibility of ultrasonographic imaging of fetal tympanic rings. METHODS: This was an observational cohort study of 80 healthy fetuses in low-risk pregnancies, divided into four gestational-age subgroups (12, 16, 23 and 32 weeks), each comprising 20 consecutive fetuses. Tympanic ring visualization was achieved by two-dimensional and three-dimensional (3D) sonography. A standard algorithm for tympanic ring examination was constructed using 3D multiplanar reconstruction. The volume acquisition plane was directed to the inferolateral aspect of the fetal temporal bone. Transvaginal scans were carried out in the 12-week and 16-week subgroups, and transabdominal scans in the 23-week and 32-week subgroups. Study parameters included the inferomedial inclination angle (IMIA) of the tympanic ring relative to the vertical skull axis, the anteromedial inclination angle (AMIA) of the tympanic ring relative to the anteroposterior skull axis and the longest (LTRD) and shortest (STRD) tympanic ring diameter, the latter measured perpendicular to the LTRD. The feasibility of tympanic ring demonstration was assessed in each gestational-age subgroup. RESULTS: Tympanic rings appeared as round-oval, thin, echogenic structures in a plane tangential to the inferolateral surface of the fetal skull below the inferior border of the squamous part of the temporal bone. Higher demonstration rates were achieved in the 16-week and 23-week subgroups (90% and 80%, respectively) than in the others. LTRD and STRD each showed a linear correlation with gestational age (r = 0.96 for both measurements; P < 0.01). Mean IMIA ranged from 41.0 to 60.4° and mean AMIA from 17.3 to 23.4° across the different gestational-age subgroups. The malleal manubrium was observed only in examinations in the second half of pregnancy, appearing as a bright echo within the upper area of the tympanic ring in 56% (9/16) and 82% (9/11) of cases with tympanic ring imaging appropriate for measurement of the study parameters in the 23-week and 32-week subgroups, respectively. CONCLUSION: This is the first report of sonographic imaging of fetal tympanic rings and shows that this is feasible in the second trimester. We discuss the possible implications of our findings for the prenatal diagnosis of congenital hearing loss.

Numerical modelling and analysis of peripheral airway asymmetry and ventilation in the human adult lung.

We present a new one-dimensional model of gas transport in the human adult lung. The model comprises asymmetrically branching airways, and heterogeneous interregional ventilation. Our model differs from previous models in that we consider the asymmetry in both the conducting and the acinar airways in detail. Another novelty of our model is that we use simple analytical relationships to produce physiologically realistic models of the conducting and acinar airway trees. With this new model, we investigate the effects of airway asymmetry and heterogeneous interregional ventilation on the phase III slope in multibreath washouts. The model predicts the experimental trend of the increase in the phase III slope with breath number in multibreath washout studies for nitrogen, SF(6) and helium. We confirm that asymmetrical branching in the acinus controls the magnitude of the first-breath phase III slope and find that heterogeneous interregional ventilation controls the way in which the slope changes with subsequent breaths. Asymmetry in the conducting airways appears to have little effect on the phase III slope. That the increase in slope appears to be largely controlled by interregional ventilation inhomogeneities should be of interest to those wishing to use multibreath washouts to detect the location of the structural abnormalities within the lung.

Quantitative assessment of chronic lung disease of infancy using computed tomography.

The aims of this study were to determine whether infants and toddlers with chronic lung disease of infancy (CLDI) have smaller airways and lower lung density compared with full-term healthy controls. Multi-slice computed tomography (CT) chest scans were obtained at elevated lung volumes during a brief respiratory pause in sedated infants and toddlers; 38 CLDI were compared with 39 full-term controls. For CLDI subjects, gestational age at birth ranged from 25 to 29 weeks. Airway size was measured for the trachea and the next three to four generations into the right lower lobe; lung volumes and tissue density were also measured. The relationship between airway size and airway generation differed between the CLDI and full-term groups; the sizes of the first and second airway generations were larger in the shorter CLDI than in the shorter full-term subjects. The increased size in the airways in the CLDI subjects was associated with increasing mechanical ventilation time in the neonatal period. CLDI subjects had a greater heterogeneity of lung density compared with full-term subjects. Our results indicate that quantitative analysis of multi-slice CT scans at elevated volumes provides important insights into the pulmonary pathology of infants and toddlers with CLDI.

Computed tomography score and pulmonary function in infants with chronic lung disease of infancy.

Chronic lung disease of infancy (CLDI) remains a common outcome among infants born extremely prematurely. In older children and adults with lung disease, pulmonary function and computed tomography (CT) scores are used to follow up respiratory disease and assess disease severity. For infants and toddlers, however, these outcomes have been used very infrequently and most often, a dichotomous respiratory outcome (presence or absence of CLDI) is employed. We evaluated the performance of CT score and pulmonary function to differentiate infants and toddlers with CLDI from a control group. CT scans, forced expiratory flows and pulmonary diffusing capacity were obtained in 39 CLDI patients and 41 controls (aged 4-33 months). CT scans were quantified using a scoring system, while pulmonary function was expressed as Z-scores. CT score outperformed pulmonary function in identifying those with CLDI. There were no significant correlations between CT score and pulmonary function. CT score had a better performance than pulmonary function in differentiating individuals with CLDI; however, these outcomes may reflect differing components of the pulmonary pathophysiology of CLDI. This new information on pulmonary outcomes can assist in designing studies with these parameters. Future studies will be required to evaluate which of the outcomes can better detect improvement with therapeutic intervention and/or lung growth.

Chronic continuous positive airway pressure (CPAP) reduces airway reactivity in vivo in an allergen-induced rabbit model of asthma.

Previous studies have demonstrated that chronic mechanical strain produced by continuous positive airway pressure (CPAP) reduces in vivo airway reactivity in rabbits and ferrets. For CPAP to potentially have a therapeutic benefit for asthmatic subjects, the reduction in airway responsiveness would need to persist for 12-24 h after its discontinuation, require application for only part of the day, and be effective in the presence of atopic airway inflammation. In the present study, airway responsiveness to acetylcholine or methacholine was measured during mechanical ventilation following three different protocols in which active, nonanesthetized, tracheotomized rabbits were treated with High vs. Low CPAP (6 vs. 0 cmH(2)O). 1) High CPAP was applied continuously for 4 days followed by 1 day of Low CPAP; 2) High CPAP was applied at night and Low CPAP during the daytime for 4 days, and 3) High CPAP was applied for 4 days in animals following ovalbumin (Ova) sensitization and challenge. For all three protocols, treatment with High CPAP resulted in significantly reduced airway responsiveness compared with treatment with Low CPAP. Cumulatively, our in vivo results in rabbits suggest that high CPAP, even when applied only at night, produces a persistent reduction of airway responsiveness. In addition, CPAP reduces airway responsiveness even in the presence of atopic airway inflammation.

Long-term "protective" effect of aromatase inhibitors on the endometrium of postmenopausal breast cancer patients.

BACKGROUND: Decrement of endometrial thickness was recorded following short-term aromatase inhibitor treatment in breast cancer patients previously treated with tamoxifen. It is necessary to verify if long-term aromatase inhibitor treatment can maintain this phenomenon. METHODS: Prospective long-term comparison of the last ultrasonographic endometrial thickness measurement taken before discontinuation of long-term tamoxifen treatment in 64 postmenopausal breast cancer patients, with further repeated measurements, performed following administration of aromatase inhibitors. RESULTS: There was a significant decrement of endometrial thickness, following 36.5 +/- 15.7 months of tamoxifen treatment, from a mean value of 8.7 +/- 5.2 mm, measured at the last ultrasonographic measurement performed before discontinuation of tamoxifen treatment, down to a mean value of 6.2 +/- 4.6 mm, measured following 5.3 +/- 4.8 months of aromatase inhibitor therapy (P < 0.001). Further ultrasonographic studies revealed the same significant trend. In the first ultrasonographic study performed during aromatase inhibitor treatment, five (7.8%) patients demonstrated a significant increase of endometrial thickness. Hysteroscopy revealed a benign endometrial polyp in three patients and atrophic endometrium in the other 2. In 35 patients (54.7%), endometrial thickness was reduced following the administration of aromatase inhibitors and in 24 patients (37.5%) there was no change in endometrial thickness. With longer duration of aromatase inhibitor therapy, more patients showed decrement of endometrial thickness. CONCLUSIONS: Reversal of endometrial thickening induced by long-term tamoxifen treatment in postmenopausal breast cancer patients is maintained throughout long-term aromatase inhibitor treatment.

Lung structure and function of infants with recurrent wheeze when asymptomatic.

Infants with recurrent wheeze have repeated episodes of airways obstruction; however, relatively little is known about the structure and function of their lungs when not symptomatic. The current authors evaluated whether infants with recurrent wheeze have smaller airway lumens or thickened airway walls, as well as decreased airway function. High-resolution computed tomography images 1 mm thick were obtained at three anatomic locations at an elevated lung volume and at functional residual capacity. Forced expiratory flows were also measured in subjects with recurrent wheeze. Airway lumen, wall areas and lung tissue density were not significantly different for recurrent wheeze (n = 17) and control (n = 14) subjects; however, subjects with recurrent wheeze had lower forced expiratory flows than predicted. Similar findings were obtained when subjects were grouped by exposure to tobacco smoke. These findings indicate that infants with recurrent wheeze, as well as exposure to tobacco smoke, have lower airway function when not symptomatic. The lower forced expiratory flows may result from a degree of airway narrowing that could not be resolved with the methodology employed or from other mechanisms, such as more collapsible airways or decreased pulmonary elastic recoil.

Hydrometrocolpos--diagnostic and therapeutic dilemmas.

Congenital distal vaginal obstruction is a rare condition, usually asymptomatic until menarche, thus often diagnosed only during puberty. Hydrometrocolpos is caused by such an obstruction, only when reasonable amounts of fluid are secreted from the mucosal lining of the genital tract. This presentation may be symptomatic and already diagnosed early in life, even during the perinatal period. There are various causes of congenital vaginal obstruction, and according to their etiology, surgical procedures may be either simple or more complicated. Timing of the surgical procedure for opening the obstruction is a dilemma. We suggest postponing the definite procedure to the menarche, when hematocolpos (accumulation of blood in the vagina) will develop, but before the further development of hematometra (accumulation of blood in the uterine cavity). This will cause stretching of the obstructed segment, will enable correct diagnosis, facilitate the procedure, and eventually minimize the complications. However, if the vaginal obstruction in neonates or in childhood is symptomatic, as in the described case, aspiration of the fluid and temporary release of the symptoms should be the optimal choice, followed by a final surgical correction latter in life.

Long-term follow-up of postmenopausal breast cancer patients following discontinuation of tamoxifen therapy.

BACKGROUND: There is a need to evaluate the extent of endometrial pathologies that might develop in postmenopausal breast cancer patients following discontinuation of tamoxifen (TAM) therapy. METHODS: The medical records of 153 postmenopausal breast cancer patients who remained untreated following discontinuation of tamoxifen therapy were evaluated for various clinical features, for endometrial thickness measurements, as detected by transvaginal ultrasonography, and for various endometrial pathologies detected. The last endometrial thickness measurement performed before discontinuation of tamoxifen was compared with endometrial thickness measured following discontinuation of tamoxifen. RESULTS: Patients were followed for 37.5+/-31.3 months. There was a gradual and significant decrement of endometrial thickness measured at the last ultrasonographic study performed before cessation of tamoxifen, compared to that observed in all four ultrasonographic studies performed following discontinuation of tamoxifen (P=0.001). Endometrial thickness gradually and significantly decreased in correlation with the time intervals of the four ultrasonographic studies performed following discontinuation of tamoxifen (P=0.001). Overall, 40 hysteroscopies were performed in 38 (24.8%) patients. No tissue was obtained in 18 (11.8%) patients. Overall endometrial pathologies were diagnosed in 22 (14.4%) patients. Benign endometrial polyps were the most frequent endometrial pathology recovered: 17 (11.1%) patients. No endometrial malignancy was diagnosed. The rate of endometrial pathologies considerably decreased with the extension of time following discontinuation of tamoxifen therapy. CONCLUSIONS: Long-term follow-up of postmenopausal breast cancer patients who remained untreated following discontinuation of TAM therapy did not reveal any malignant endometrial pathology. Only few benign endometrial pathologies were diagnosed, which became fewer in time.

Chronic inflation of ferret lungs with CPAP reduces airway smooth muscle contractility in vivo and in vitro.

The mechanical stress imposed on the lungs during breathing is an important modulator of airway responsiveness in vivo. Our recent study demonstrated that continuous positive airway pressure applied to the lungs of nonanesthetized, tracheotomized rabbits for 4 days decreased lower respiratory system responsiveness to challenge with ACh (Xue Z, Zhang L, Ramchandani R, Liu Y, Antony VB, Gunst SJ, Tepper RS. J. Appl Physiol 99: 677-682, 2005). In addition, airway segments excised from the lungs of these animals and studied in vitro exhibited reduced contractility. However, the mechanism for this reduction in contractility was not determined. The stress-induced decrease in airway responsiveness could have resulted from alterations in the excitation-contraction coupling mechanisms of the smooth muscle cells, or it might reflect changes in the structure and/or composition of the airway wall tissues. In the present study, we assessed the effect of prolonged chronic stress of the lungs in vivo on airway smooth muscle force generation, myosin light chain phosphorylation, and airway wall structure. To enhance the potential development of stress-induced structural changes, we applied mechanical stress for a prolonged period of time of 2-3 wk. Our results demonstrate a direct connection between the decreased airway responsiveness caused by chronic mechanical stress of the lungs in vivo and a persistent decrease in contractile protein activation in the airway smooth muscle isolated from those lungs. The chronic stress also caused an increase in airway size but no detectable changes in the composition of the airway wall.

Aromatase inhibitors reverse tamoxifen induced endometrial ultrasonographic changes in postmenopausal breast cancer patients.

OBJECTIVE: Aromatase inhibitors may decrease endometrial thickness in breast cancer patients previously having short-term tamoxifen treatment. There is a necessity to find out if aromatase inhibitors can also decrease endometrial thickness in patients previously treated with long-term tamoxifen treatment. METHODS: Prospective comparison of the last ultrasonographic endometrial thickness measurement taken before discontinuation of long-term tamoxifen treatment in 36 postmenopausal breast cancer patients, with further measurements, performed following aromatase inhibitors administration. RESULTS: There was a significant decrement of endometrial thickness, following 36.2 +/- 16.8 months of tamoxifen treatment, from a mean value of 9.1 +/- 5.8 mm, measured at the last ultrasonographic measurement performed before discontinuation of tamoxifen treatment, down to a mean value of 6.0 +/- 5.0 mm, measured following 5.8 +/- 5.8 months of aromatase inhibitors therapy (P = 0.001). A second ultrasonographic measurement performed in 8 patients following of additional 7.5 +/- 4.0 months of aromatase inhibitors treatment revealed further decrement of mean endometrial thickness to 4.8 +/- 2.1 mm (P = 0.002 compared to baseline). In 28 patients (77.8%), endometrial thickness was reduced following the administration of aromatase inhibitors, in four patients (11.1%) there was no change in endometrial thickness and four (11.1%) patients demonstrated an increase of endometrial thickness. CONCLUSIONS: Aromatase inhibitors may reverse endometrial thickening induced by long-term tamoxifen treatment in postmenopausal breast cancer patients.

Hemorrhagic corpus luteum is associated with ovarian edema.

BACKGROUND: Most cases of ovarian edema are thought to result from intermittent ovarian/adnexal torsion. This study describes how, in some cases, this etiology was ruled out even though the edema was unexplained. STUDY OBJECTIVE: To evaluate the association between ovarian edema and hemorrhagic corpus luteum. SETTING: Department of gynecology in an urban medical center. PARTICIPANTS: Five patients admitted to the department of gynecology with a sonographic diagnosis of ovarian edema of unexplained etiology. RESULTS: Laparoscopy performed on three of five patients in whom a diagnosis of unexplained ovarian edema revealed hemorrhagic corpus luteum and ovarian edema. The remaining two patients displayed typical sonographic imaging of hemorrhagic corpus luteum and ovarian edema and they were managed expectantly. The affected ovaries were between 4.8 and 10 times larger than the unaffected ovaries. During follow-up, the affected ovaries returned to their normal size and appearance. CONCLUSIONS: Hemorrhagic corpus luteum can cause ovarian edema without interrupting the blood flow supply. The outcome of expectant management without any surgical intervention is the gradual disappearance of the ovarian edema in these patients and the return of ovaries to a normal sonographic appearance.

Hydrosalpinx with adnexal torsion in an adolescent virgin patient--A diagnostic dilemma: case report and review of the literature.

Hydrosalpinx is one of the predisposing factors of adnexal torsion. However, because the incidence of hydrosalpinx in adolescent virgin patients is very rare, it may cause diagnostic dilemma, leading sometimes to suboptimal treatment. We present the case of an 18-yr-old female, not sexually active, presenting with acute lower right abdominal pain. The working diagnosis was of a simple ovarian cyst, so aspiration was performed. Abdominal symptoms reoccurred and sonography revealed a large hemorrhagic cystic mass adjacent to an edematous right ovary. The patient was referred to immediate laparoscopy due to suspected right adnexal torsion. On laparoscopy, the right adnexa was twisted three times causing an edematous ovary with a hematosalpinx. Detorsion was performed. Five weeks later, transabdominal ultrasound reviled normal bilateral ovaries and the hematosalpinx disappeared. In conclusion, hydrosalpinx, although very rare in adolescence, must be considered in the differential diagnosis. Aspiration in such cases is not the treatment of choice and moreover, it may cause complications.

Thumb replantation: a retrospective review of 103 cases.

Replantation has become the state of the art reconstruction for an amputated thumb. The aim of our study was to review our series of thumb replantations over a period of 12 years at the Bellevue Hospital Center in New York City. The mechanism of injury, level of amputation, and use of vein grafts was reviewed and correlated with survival rates of the replanted thumbs. The overall survival rate was 91.3%. Of the 12 thumbs that were re-explored for vascular compromise, 75% were successfully salvaged. Our study also indicates that there is no statistical difference in survival of thumb replants when comparing the mechanism of injury, the level of amputation, and the use of vein grafts. However, the use of vein grafting seemed to be beneficial in the successful outcome of replantation in severe crush and avulsion injuries, even though the values did not reach statistical significance. We conclude that thumb replantation is associated with very high survival rate, regardless of the mechanism of injury or level of amputation, and should be attempted in all cases. An early reexploration for vascular problems yields a high salvage rate and should be performed in all cases. We also recommend the use of vein grafts in severe crush and avulsion injuries.

Respiratory system responsiveness in rabbits in vivo is reduced by prolonged continuous positive airway pressure.

Active, nonanesthetized, tracheotomized rabbits were subjected to continuous positive airway pressure (CPAP) for 4 days to determine the effects of chronic mechanical strain on lung and airway function. Rabbits were maintained for 4 days at a CPAP of 6 cmH(2)O (high CPAP), at a CPAP of 0 cmH(2)O (low CPAP), or without tracheostomy (no CPAP). After treatment with CPAP, changes in respiratory resistance in response to increasing concentrations of inhaled ACh were measured during mechanical ventilation to evaluate respiratory system responsiveness in vivo. Intraparenchymal bronchial segments were isolated from the lungs of all animals to evaluate airway smooth muscle responsiveness and bronchial compliance in vitro. Rabbits maintained for 4 days at high CPAP demonstrated significantly lower responsiveness to ACh compared with rabbits that were maintained at low CPAP or with no CPAP. Airways isolated from the lungs of animals subjected to the chronic application of high CPAP were also less responsive to ACh in vitro than the airways isolated from animals subjected to low CPAP or no CPAP. The persistence of the decreased responsiveness in the excised airway tissues suggests that the decreased respiratory system responsiveness observed in vivo results primarily from direct effects on the airways. The results demonstrate that the application of prolonged mechanical strain in vivo can reduce airway reactivity.

Chronic strain alters the passive and contractile properties of rabbit airways.

Pathophysiological conditions of the lung may shift the balance of forces so as to chronically alter the amount of strain imposed on the airways. This chronic strain could result in changes in the structure and/or function of the airways that affect its physiological properties. We evaluated the effects of imposing physiological levels of chronic mechanical strain on the passive and active physiological properties of intraparenchymal rabbit airways. Isolated bronchial segments were cultured for 48 h at transmural pressures of 0 cmH(2)O (No Strain) or 7 cmH(2)O (Strain). Effects of strain on small parenchymal airways were evaluated in lung tissue slices cultured under conditions of No Strain or approximately 50% increased in diameter (Strain). Chronic strain resulted in a higher passive compliance of the bronchial segments and larger airway lumen size. In addition, bronchi not subjected to chronic Strain were more responsive to ACh than bronchi subjected to chronic Strain, and airways in lung slices subjected to No Strain narrowed more in response to ACh than airways in lung slices subjected to Strain. The greatest effects of chronic strain occurred in the smallest sized airways. Our results suggest that chronic distension of the airways has physiologically important effects on their passive and active properties, which are most prominent in the smaller, more peripheral airways.