Vitrectomy with peeling of the inner limiting membrane for treating diabetic macular edema.

PURPOSE: to evaluate the results of pars plana vitrectomy with peeling of the inner limiting membrane (ILM stained with infracyanine green (IfCG) in 26 patients with diabetic macular edema, and to identify which factors are associated with a better postoperative visual outcome. PATIENTS AND METHODS: 26 patients with diabetic macular edema were included in the study. A pars plana vitrectomy with ILM peeling stained with IfCG was performed, in some cases combined with cataract surgery. In 22 patients the ILM was retained, examined with electron microscopy and compared with normal ILM's. Visual acuity and fundus examination were recorded several months after surgery. To determine which factors lead to the best postoperative results, patients were divided into different groups and compared. RESULTS: during surgery, a taut posterior hyaloid was found in 26 patients, which was successfully detached in all cases. ILM peeling within the vessel arcade succeeded in all patients. Postoperative examination showed improved visual acuity and decreased macular edema in 19 patients, unaltered visual acuity in 3 patients and decreased visual acuity in 4 patients. Comparison between different groups of patients revealed that young patients with recent vision loss and without previous macular laser treatment, had better postoperative results. Electron microscopical examination showed a more condensed ILM in diabetic patients, consisting of a layer of fine curled fibers. CONCLUSION: pars plana vitrectomy with peeling of the ILM stained with IfCG leads to good postoperative results in young diabetic patients with recent vision loss due to macular edema and without previous macular laser treatment.

Stereological estimation of number and volume of pulmonary neuroepithelial bodies (NEBs) in neonatal hamster lungs.

The number and volume of pulmonary neuroepithelial bodies (NEBs) of 1- and 4-week-old hamsters were estimated using unbiased stereological principles and systematic sampling techniques. For comparative purposes, volume estimations were also made in the carotid body, the parathyroid gland, and the adrenal medulla. A significant decrease was found in the total number of NEBs, immunoreactive for CGRP, between 1 and 4 weeks. Individual as well as cumulative NEB volume also decreased significantly. The cumulative NEB volume in 1-week-old hamsters was in the same range as the volumes of the carotids and parathyroids in the same animals. The postnatal decrease of the NEB number suggests that the NEBs are of primary potential importance in the neonatal stage, when they may complement the chemoreceptor function of the carotid bodies, which are relatively inactive at birth. Since the cumulative NEB volume (at least at the age of 1 week) is equal to that of the carotid bodies and the parathyroids, their physiological function may be of similar importance.

Immunoreactivity for the alpha-subunit of the pituitary glycoprotein hormones in pulmonary neuroendocrine cells of developing human lung and various perinatal diseases.

Infant lung tissue, obtained at autopsy, was studied by immunohistochemistry for the presence of pituitary glycoprotein hormones (PGHs) in the lung. The infants, born at term or preterm, died of various causes. The results provide the first immunological evidence of the presence of the common a-subunit of the pituitary glycoprotein hormones (alphaPGH) in the lung. The immunoreactivity is located in the pulmonary neuroendocrine cells and neuroepithelial bodies. In addition, the cells labelled by alphaPGH antisera (alphaPGH cells) form a subpopulation of the neuroendocrine cells detected by anti-calcitonin immunohistochemistry (CT cells). Moreover, the number of alphaPGH cells appears to increase after neonatal pneumonia or when the number of CT cells is elevated following the development of disease. Also, the weak staining of one of the monoclonal antibodies against the specific b-subunit of thyrotropin (TSH) might, in combination with the increased detectability of a-subunits, indicate that TSH can be endogenously produced in the lung.

Na+/H+ exchange inhibition improves long-term myocardial preservation.

BACKGROUND: Na+/H+ exchange plays an important role in the ionic changes observed during myocardial ischemia and reperfusion. We investigated the cardioprotective efficacy of a selective Na+/H+ exchange inhibitor, 4-isopropyl-3-methylsulfonyl-benzoylguanidin-methanesulfonate (HOE642), in a canine model of long-term heart preservation. METHODS: Canine donor hearts were stored for 24 hours in hyperkalemic crystalloid cardioplegic solution; in cardioplegic solution enriched with HOE642; in cardioplegic solution enriched with HOE642, with donor and recipient treated with HOE642; in standard cardioplegic solution, with donor and recipient treated with HOE642; or in standard cardioplegic solution, with only the recipient treated. After orthotopic transplantation, pressure-volume relationships were obtained and dogs were weaned from bypass. Morphology was studied. RESULTS: Myocardial compliance was well preserved when donor and recipient were treated. These groups had the lowest myocardial water content, and no morphologic signs of irreversible damage. In these groups, weaning from cardiopulmonary bypass was successful in 10 of 10 animals, with a cardiac index around 2 L x min(-1) x m(-2). Only 3 of 5 animals in each of the other three groups could be weaned, with significantly lower cardiac indices. CONCLUSIONS: Treatment with HOE642 in both donor and recipient improves myocardial compliance, postweaning cardiac index, and ultrastructure of donor hearts preserved for 24 hours and orthotopically transplanted.

Calcification characteristics of porcine stented valves in a juvenile sheep model.

BACKGROUND: Different antimineralization treatments of stented porcine bioprostheses were evaluated: ethanol (Epic), alpha-amino-oleic acid (AOA) (Mosaic), and sodium dodecyl sulfate (SDS) (Hancock II). A nontreated, glutaraldehyde-fixed valve (Labcor) served as control. METHODS: For each treatment, six valves were implanted in juvenile sheep in the pulmonary position. Valves were explanted after 3 and 6 months and examined macroscopically, by roentgenogram and light and transmission electron microscopy. Calcium content (microg/mg) was determined by atomic absorption spectrometry. RESULTS: The Labcor valves revealed small calcium deposits in the cusps, although calcium content remained low (median value 0.4+/-0.8 microg/mg). SDS did not prevent cusp calcification as assessed by histology and calcium content measurement, which was higher than in all other valves: 1.9+/-4.6 microg/mg (p < 0.05). Cusp retraction and rupture were occasionally found in the Hancock. The Mosaic and Epic valves showed no cusp calcification and had low calcium contents (0.3+/-2.4 microg/mg and 0.7+/-0.6 microg/mg, respectively). Epic showed less pannus formation, but had hematoma or iron staining in the cusps. CONCLUSIONS: SDS is inefficient as an antimineralization treatment, in contrast to ethanol or AOA. Cusp hematoma after ethanol treatment needs further investigation.

Sleeve-related thrombosis: a new form of catheter-related thrombosis.

In a detailed study of central venous catheter-related sleeve and thrombosis in experimental animals, a new form of thrombosis was detected and termed sleeve-related thrombosis. A silastic catheter was placed in the jugular vein and the anterior vena cava of 22 rabbits and 54 rats. After intervals of 1, 3, 7 days, 2, 3, 4 weeks and 1, 2, 4, 6 months the veins were examined by light microscopy and by transmission electron microscopy. In about 50% of the rats a thrombus was observed at the end of the catheter sleeve. Consecutive cutting allowed the visualization of a transition from a sleeve via part of sleeve and part of thrombus to a pure thrombus. This thrombus was separated from the vein wall and could not be considered a mural thrombus. As the thrombus was only attached to the terminal part of the organized catheter sleeve we propose the name sleeve-related thrombosis.

Sulphated and sulphonated polymers inhibit the initial interaction of hepatitis B virus with hepatocytes.

The initial step during hepatitis B virus (HBV) infection is the specific attachment of the virus to the hepatocyte. Here we studied whether the binding of HBV to hepatocytes can, as is the case with most other enveloped viruses, be blocked by polyanionic compounds. Viral particles produced by HepAD38 cells were used as inoculum and HBV-negative HepG2 cells, as well as primary human hepatocytes, as target cells. Three sulphated polymers, that is, PAVAS (a co-polymer of acrylic acid with vinyl alcohol sulphate), heparin and dextran sulphate (DS) (MW 5000), and the sulphonated polymer PAMPS [poly(2-acryl-amido-2-methyl-1-propanesulfonic acid] (MW approximately 7000-12000), proved strong inhibitors of the binding of HBV to HepG2 cells and primary hepatocytes. The 50% effective concentration (EC50) for inhibition of HBV binding to HepG2 cells by PAVAS, heparin, DS and PAMPS was 1.3 microg/ml, 1.6 microg/ml, 1.8 microg/ml and 3.3 microg/ml, respectively, and to primary hepatocytes 1.6 microg/ml (PAVAS), 1.6 microg/ml (heparin), 2.6 microg/ml (DS) and 4.1 microg/ml (PAMPS). These values are in the same range as the concentrations required for these compounds to prevent such viruses as herpesviruses and HIV from binding to cells. These findings may be helpful in elucidating the mechanism of the initial interaction of HBV with hepatocytes.

Innervation of rabbit intrapulmonary neuroepithelial bodies. Quantitative and qualitative ultrastructural study after vagotomy.

The purpose of this study was to locate the cell bodies of origin of the intracorpuscular nerve endings of the intrapulmonary neuroepithelial bodies (NEB). Left infra- or supranodosal vagotomy was performed on 35 young rabbits. In control animals, the NEB innervation index (i.e. the ratio of the number of intracorpuscular nerve endings to the number of NEB corpuscular epithelial cells) was 0.3 in both left and right lungs. Left infranodosal vagotomy decreased the NEB innervation index in the left lung to 0.1 by 24 h postoperatively. Degenerating nerve endings displaying neurofilamentous hyperplasia, were found among the few surviving nerve endings. Left supranodosal vagotomy did not influence the innervation of the NEB of the left lung, even at 5 days postoperatively. In the right lungs, neither procedure had significant effects. These findings indicate that the NEB are predominantly innervated by sensory nerve fibers, derived from cell bodies in the nodose ganglion of the vagus nerve. This neuroanatomical argument corroborates our hypothesis that NEB represent intrapulmonary neuroreceptors.

Double vital staining using trypan blue and infracyanine green in macular pucker surgery.

AIMS: To study the clinical properties of double vital staining in premacular fibrosis, facilitating complete removal of all epiretinal tissue. METHODS: In a two step surgery, the epiretinal pucker was removed after staining with trypan blue, whereafter the inner limiting membrane was peeled after staining with infracyanine green. RESULTS: In all 30 patients, a separate epiretinal layer and inner limiting membrane were removed from the macular area. Pathological examination showed different histological properties of the removed layers. An increased visual acuity was measured in 26 patients, and a slightly decreased visual acuity in one patient. CONCLUSION: The described double staining technique could be a novel valuable tool that may help to achieve optimal anatomical and functional recovery after surgery for premacular fibrosis

Are stentless aortic heterografts suitable for right ventricular outflow tract reconstruction? An experimental study in juvenile sheep.

Allograft valved conduits are used routinely for reconstruction of the right ventricular outflow tract in children with congenital heart disease; however, allografts are scarce. The purpose of this study was to evaluate two stentless aortic valves that might be suitable alternatives for right ventricular outflow tract reconstruction. Twelve juvenile sheep underwent implantation of stentless aortic heterografts as an interposition in the pulmonary artery: six porcine aortic valves (Freestyle) and six fully pericardial valves (Pericarbon stentless). In each series, three valves were explanted after 3 months, the other three after 6 months. Valves were analyzed by gross inspection, radiography, and light microscopy. The porcine aortic stentless valve (Freestyle) showed extensive calcification of its aortic wall portion, with perfectly functioning, pliable cusps without calcification or fibrous overgrowth up to 6 months. The pericardial valves (Pericarbon stentless) showed extensive fibrous sheathing, causing progressive retraction of the leaflets and severe regurgitation. After 3 months, minimal calcification was seen in the pericardial wall. Calcification was more pronounced after 6 months, sometimes causing complete calcification of pericardial wall and leaflets, leading to a significant stenosis. We conclude that the pericardial stentless valve becomes rapidly dysfunctional after right-sided implantation as a result of fibrous sheathing and severe calcification. The porcine aortic stentless valve remains functional, but severe calcification of the aortic wall portion is problematic.

The No-React anticalcification treatment: a comparison of Biocor No-React II and Toronto SPV stentless bioprostheses implanted in sheep.

Calcification of stentless aortic heterografts still limits the use of these bioprostheses in young patients despite their superior hemodynamic profile. The No-React treatment is described as an anticalcification treatment for biomaterials. We compared the Biocor No-React treated stentless bioprosthesis with the routine glutaraldehyde-fixed Toronto SPV bioprosthesis in a juvenile sheep model. Toronto SPV or Biocor No-React valves were implanted in pulmonary position in juvenile sheep (n = 6). The valves were explanted after 3 months and analyzed by gross inspection, x-ray studies, histological examination, and transmission electron microscopy. The Toronto SPV valve showed calcification of the aortic wall portion at both the inflow and outflow sides of the valve. No significant calcification of the cusps was found by gross inspection or by radiographic or histological examinations. Calcification was visible with electron microscopy in cell remnants and between collagen fibers in the cusps. The Biocor No-React valve showed extensive calcification of the residual aortic wall portion that is contained in the valve. With x-ray and histological examinations, clear calcification of the pericardial wrap, largely replacing the aortic wall tissue, was seen. Calcification scattered throughout the cusp was seen by electron microscopy. We conclude that the Biocor No-React process did not prevent calcification of glutaraldehyde-fixed stentless bioprostheses in a juvenile sheep experimental model. Furthermore, replacement of a large part of the aortic wall by a pericardial wrap did not prevent calcification of the stentless valve "wall."

Pulmonary neuroepithelial bodies are innervated by vagal afferent nerves: an investigation with in vivo anterograde DiI tracing and confocal microscopy.

The pulmonary airway and alveolar epithelia contain distinctly innervated clusters of basally granulated cells: the neuroepithelial bodies. In the past, morphological criteria and the results of selective vagotomy have led to the interpretation that their innervation is sensory. Consequently, they are regarded as receptor organs. As a further test of this hypothesis, the present investigation set out to label vagal sensory nerve fibres to the lungs by anterograde neural tracing, and to establish the relationship between these fibres and the neuroepithelial bodies. A fluorescent neural tracer was injected unilaterally into the left or right nodose ganglion of adult rats. After suitable survival times, thick frozen sections of lung tissue were studied with laser scan confocal microscopy. Sensory nerve fibres were seen to run in the airway walls and occasionally penetrated the epithelium, where they formed complex terminals. The resulting intraepithelial sensory end organs showed a close morphological resemblance to the neuroepithelial bodies. Subsequently, electron microscopic investigation of such identified structures revealed the typical ultrastructural characteristics of neuroepithelial bodies: corpuscular cells containing dense cored secretory vesicles and contacted by mitochondria-rich nerve endings. We conclude that anterograde tracing of sensory nerves from the nodose ganglion confirms the receptor nature of the pulmonary neuroepithelial bodies, which may correspond to a subpopulation of the irritant and C-fibre receptors.

Antimineralization treatments in stentless porcine bioprostheses: an experimental study.

BACKGROUND AND AIM OF THE STUDY: Photo-oxidation treatment of porcine stentless bioprostheses (Photofix) was compared with glutaraldehyde fixation, with either AOA (Freestyle valve) or Tween-80 (Edwards Prima Plus valve). METHODS: Six valves of each type were implanted in juvenile sheep, in the pulmonary position. Valves were explanted after three or six months and examined macroscopically, by X-radiography, and by light and transmission electron microscopy. Calcium content was determined by atomic absorption spectrometry. RESULTS: The cusps of all valves were free of calcification, and had normal histology and function. Calcium contents (median +/- IQR) were 0.63+/-0.45, 0.73+/-1.46 and 0.46+/-1.42 microg/mg for the Photofix, Freestyle and Prima Plus valves, respectively (p = NS). Calcium contents of the aortic wall portions were 0.71+/-1.27 (Photofix), 10.78+/-77.22 (Freestyle) and 28.70+/-66.53 (Prima Plus) (p <0.05 for Photofix versus Freestyle or Prima Plus). CONCLUSION: Photo-oxidation of a porcine stentless valve prevents calcification not only in the cusps, but also in the aortic wall portion.

The influence of stenting on the behavior of amino-oleic acid-treated, glutaraldehyde-fixed porcine aortic valves in a sheep model.

BACKGROUND AND AIM OF THE STUDY: The durability of freehand-sewn aortic valve homografts used for valve replacement in humans is greater than for stented aortic homografts. In analogy with this, it is expected that the durability of a stentless heterograft will be superior to that of its stented counterpart. Our objective was to investigate the influence of stenting on amino-oleic acid (AOA)-treated, glutaraldehyde-fixed porcine aortic valve bioprostheses. METHODS: Twelve young sheep underwent implantation of porcine aortic valves in the pulmonary artery: six porcine aortic stentless valves (Freestyle) and six porcine aortic stented valves (Mosaic). In each series, three valves were explanted after three months, and three after six months. Valves were analyzed by gross inspection, radiography, histology, and transmission electron microscopy. Quantitative determination of calcium content was made with atomic absorption spectrometry. RESULTS: The porcine aortic stentless valve showed extensive calcification of its aortic wall portion, but had perfectly functioning, pliable cusps without calcification up to six months. The cusps of porcine aortic stented valves were also pliable and functioning without calcification up to six months. Only minimal calcification was seen in the aortic wall of the stented valves. At six months after implantation the cusps of stentless valves contained significantly less calcium than those of stented valves (2.7+/-1.2 microg/mg and 7.9+/-2.3 microg/mg, respectively; p = 0.011). However, the aortic wall from stentless valves contained significantly more calcium than that of stented valves (three-month explants: 39.2+/-14.4 versus 7.2+/-2.8 microg/mg; p <0.05; six-month explants: 49.3+/-14.0 versus 14.1+/-5.9 microg/mg; p <0.05). CONCLUSION: These data suggest that stenting does influence cuspal calcification of AOA-treated, glutaraldehyde-fixed porcine aortic valves.

Calcification characteristics of porcine stentless valves in juvenile sheep.

OBJECTIVE: To compare calcification characteristics of two porcine stentless valves (Toronto SPV and Freestyle) with different designs, fixation and antimineralization techniques using a juvenile sheep model of valve implantation inside the circulation. METHODS: The stentless valves (n = 2 x 6) were implanted in juvenile sheep in the pulmonary artery as an interposition, while the circulation was maintained with a right ventricular assist device. The model was validated by the implantation of, clinically well-known, porcine (Hancock II) and pericardial (Pericarbon) valves. Half of the valves were explanted after 3 months, the rest after 6 months. Valves were examined macroscopically, by X-ray, light microscopy (HE, Masson, Von Giesson, Von Kossa, PTAH stains), and transmission electron microscopy. Quantitative determination of the calcium content of the cusps was performed with atomic absorption spectrometry. RESULTS: After 3 months, the Freestyle had an extensively calcified aortic wall, most prominent at the outflow side of the porcine valve. After 6 months, calcification increased transmurally, but the valve cusps were free of calcification, and the inflow side was only slightly calcified. The Toronto SPV valve also started to calcify at the inflow side of the valve after 3 months with increased calcification after 6 months. The base of the Toronto SPV valve cusps showed slight calcification after 6 months of implantation. CONCLUSIONS: The pattern of calcification of the porcine aortic wall differs between the two studied stentless valves, with calcification located predominantly at the outflow side in the Freestyle valve, but also at the inflow side in the Toronto SPV valve. The cusps of the Freestyle valve were less prone to calcification than those from the Toronto SPV valve.

[Microfluorimetric study of the effect of almitrine bismesylate (Vectarion) on intrapulmonary neuroepithelial bodies]. / Etude microfluorimétrique de l'action du bismésilate d'almitrine (Vectarion) sur les corps neuro-épithéliaux intrapulmonaires.

As Almitrine bismesylate is a potent peripheral chemo-receptor stimulant we have studied its action, after intra-peritoneal injection, on the intra-neuro-epithelial bodies (NEB) of 24 young rabbits (4 to 17 days old) measuring the intensity of the cytoplasmic fluorescence. The administration of Almitrine bismesylate in pharmacological doses provoked a marked rise (around 25%) in the intensity of fluorescence of NEB compared to a placebo group, indicating a raised cytoplasmic concentration of serotonin. These observations show that Almitrine bismesylate, in stimulating all the peripheral chemo-receptors equally, influences the NEB at the same time corroborating the intra-pulmonary chemoreceptor mature of the latter. The mechanism of action of Almitrine bismesylate on the NEB remains unexplained at a cellular level. Some supplementary studies are planned to elucidate these aspects.

Pulmonary neuroendocrine cells (PNEC) and neuroepithelial bodies (NEB): chemoreceptors and regulators of lung development.

The airway and alveolar epithelia contain pulmonary neuroendocrine cells whose structure indicates an endocrine function. They are also in contact with sensory nerve fibres. These cells often aggregate into distinct corpuscles-neuroepithelial bodies-and carry membrane receptors sensitive to a number of stimuli, including hypoxia and nicotine. They synthesise, store and release a number of bioactive substances such as serotonin, calcitonin gene-related peptide and the mitogen bombesin. When these are released they contribute to redistribution of pulmonary blood flow, regulation of bronchomotor tone, modulation of the immune response, stimulation of sensory nerve fibres and regulation of lung growth and development. Pulmonary neuroendocrine cells and neuroepithelial bodies seem to be most important in the fetal and neonatal lung as regulators of airway development and hypoxia-sensitive chemoreceptors. There is a link between these cells and specific types of lung cancer and their involvement in lung and paediatric pathology may be profound.

Epithelio-stromal interactions in neonatal hamster bronchioles: morphology and distribution of epithelial foot processes and their possible relation to epithelial growth inhibition.

Morphology and distribution of epithelial foot processes (FP) were studied in hamster neonatal lung bronchioles. To correlate them with growth, bronchiolar mitotic index was determined, rat small intestine used as a reference tissue and the distribution of foot processes compared to the distribution of immunoreactivity against proliferating cell nuclear antigen (PCNA). In bronchioles, where growth occurs through dispersed mitoses, FP also occur dispersed throughout the whole perimeter of the epithelium; whereas in small intestine, where growth is localised in a specific region (crypts), FP are likewise confined to a distinct, but different, zone (villi). Staining the bronchioles for PCNA labels dispersed grouplets of nuclei; most of which being only weakly stained. In the intestines, strong immunostaining mainly occurs in the crypts, while the villi mainly display a weak nuclear stain. Additionally, in both types of tissue the distribution of FP and weak PCNA staining are parallel. Thus, an apparent association between FP, lack of proliferation and nucleoplasmic PCNA staining arises; the basis of which being presently unclear. However, a possible interrelating factor might be a growth inhibitory influence of epithelio-stromal interactions on the epithelial cells.

Ultrastructure of nerve endings and synaptic junctions in rabbit intrapulmonary neuroepithelial bodies: a single and serial section analysis.

This study on the innervation of rabbit intrapulmonary neuroepithelial bodies (NEB) was undertaken to obtain more information about the detailed ultrastructure of morphologically afferent and efferent intracorpuscular NEB nerve endings, the extent to which they are in cytoplasmic continuity with one another, and the structure of the synaptic junctions they form with the NEB corpuscular cells. As in earlier studies, NEB exhibit intracorpuscular nerve endings containing predominantly either mitochondria (morphologically afferent) or synaptic vesicles (morphologically efferent). Both types of nerve endings form synaptic junctions with the NEB corpuscular cells, arranged so that a NEB corpuscular cell is the presynaptic element and the nerve ending the postsynaptic element. This arrangement implies that NEB can transmit nerve impulses to the central nervous system, thus arguing in favour of their hypothetical neuroreceptor function. Moreover, on serial sections, the morphologically afferent and efferent intracorpuscular nerve endings are often found in cytoplasmic continuity. Hence, transduction of stimuli in the NEB implies concomitant efferent modulation of the NEB corpuscular cells. In conclusion, intrapulmonary NEB apparently function as neuroreceptors that are locally modulated by axon reflexes.

Effect of various vagotomy procedures on the reaction to hypoxia of rabbit neuroepithelial bodies: modulation by intrapulmonary axon reflexes?

Recent neuroanatomical investigations revealed the intrapulmonary neuroepithelial bodies (NEB) to be innervated to a large extent by sensory nerve fibers, displaying peripheral nerve endings of afferent as well as efferent morphology and having their cell bodies in the nodose ganglion of the vagus nerve. Earlier studies also revealed that upon exposure to acute hypoxia NEB exhibit a distinct secretory response, including as well a decrease in the cytoplasmic fluorescence as an increased basal exocytosis and indicating the secretion of serotonin. In the present study, we have tried to establish whether or not this secretory behavior is neurally controlled by combining an exposure to hypoxia with various vagotomy procedures. After long-term (3 days) infranodose vagotomy, the ipsilateral NEB nerve endings have degenerated. The secretory response to hypoxia is modified: the cytoplasmic fluorescence intensifies, while the basal exocytosis remains unchanged. After short-term (1 hour) infranodose as well as long-term (3 days) supranodose vagotomy, the NEB nerve endings are still intact, though no longer connected to the central nervous system. In these circumstances, the hypoxic NEB secretory behavior is indistinguishable from that of intact NEB. From these experimental findings we conclude that the hypoxic NEB secretory response is neurally controlled, since it no longer occurs when the normal innervation has degenerated. This modulation is however not by CNS motor nerve impulses, but probably by intrapulmonary axon reflexes in sensory nerve fibers.