Experimental Acid-Aspiration Pneumonia in the Rabbit

Four anesthetized rabbits given intratracheal injections of hydrochloric acid, pH 1.5, 2 ml/kg, were killed 4 h later. A fifth rabbit was an untreated control. Each lung had a few red-brown patches of compression atelectasis. Microscopically, treated lungs had a severe exudative necrotizing bronchitis, bronchiolitis, and alveolitis. There was also intra-alveolar hemorrhage and edema. Electron microscopy showed folds, projections and focal swellings of type I cells lining affected alveoli. A morphometric study showed 69% of parenchyma to be normal, 26% edematous and 5% hemorrhagic. In the airways 58% of the epithelium was damaged.

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A morphometric study of the carotid body in chronically hypoxic rats

Journal of Applied Physiology ◽

10.1152/jappl.1984.57.5.1430 ◽

1984 ◽

Vol 57 (5) ◽

pp. 1430-1438 ◽

Cited By ~ 93

Author(s):

K. H. McGregor ◽

J. Gil ◽

S. Lahiri

Keyword(s):

Blood Vessels ◽

Carotid Body ◽

Structural Changes ◽

Volume Density ◽

Morphometric Study ◽

Type I ◽

Type Ii Cells ◽

Type Ii ◽

Type I Cells ◽

I Cells

We performed morphometric studies of carotid body in acutely and chronically hypoxic rats (inspired PO2 = 70 Torr, at sea level). Acute exposure was for the duration of about 10 min, and chronic exposure lasted for 28 days. We confirmed that the total volume of the organ increased by severalfold. At the light-microscopy level we found an enlargement of the volume density of the blood sinuses from 14 to 31% due to chronic hypoxia. The morphometric hematocrit increased from 39 to 70% paralleling changes in the conventionally measured venous hematocrit. These data do not show any specific plasma skimming in the carotid body blood vessels. With the electron microscope we found that the mean average volume of type I cells increased from 320 micron3 in controls to 1,120 micron3 in the chronically hypoxic rats without hyperplasia, whereas type II cells had increased in number without alteration in size. Qualitative observations revealed that the normal appearance of clusters of ovoid type I cells interspersed by capillaries had been transformed into a pattern of individual cells forming plates between expanded blood vessels with a large increase of contact area between the cells and vessels. Type II cells appeared to have proliferated without changes in individual size to cover the enlarged periphery of type I cells. The observed structural changes in the carotid body parenchyma and vasculature appear to be physiologically adaptive and provide further support for the idea that various elements in the organ are particularly sensitive to hypoxia.

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The von Hippel-Lindau Chuvash mutation in mice causes carotid-body hyperplasia and enhanced ventilatory sensitivity to hypoxia

Journal of Applied Physiology ◽

10.1152/japplphysiol.00530.2013 ◽

2014 ◽

Vol 116 (7) ◽

pp. 885-892 ◽

Cited By ~ 10

Author(s):

Mary E. Slingo ◽

Philip J. Turner ◽

Helen C. Christian ◽

Keith J. Buckler ◽

Peter A. Robbins

Keyword(s):

Electron Microscopy ◽

Carotid Body ◽

Hypoxia Inducible Factor ◽

Autosomal Recessive Disorder ◽

Whole Body ◽

Ultrastructural Changes ◽

Type I ◽

Von Hippel Lindau ◽

Type I Cells ◽

I Cells

The hypoxia-inducible factor (HIF) family of transcription factors coordinates diverse cellular and systemic responses to hypoxia. Chuvash polycythemia (CP) is an autosomal recessive disorder in humans in which there is impaired oxygen-dependent degradation of HIF, resulting in long-term systemic elevation of HIF levels at normal oxygen tensions. CP patients demonstrate the characteristic features of ventilatory acclimatization to hypoxia, namely, an elevated baseline ventilation and enhanced acute hypoxic ventilatory response (AHVR). We investigated the ventilatory and carotid-body phenotype of a mouse model of CP, using whole-body plethysmography, immunohistochemistry, and electron microscopy. In keeping with studies in humans, CP mice had elevated ventilation in euoxia and a significantly exaggerated AHVR when exposed to 10% oxygen, with or without the addition of 3% carbon dioxide. Carotid-body immunohistochemistry demonstrated marked hyperplasia of the oxygen-sensing type I cells, and the cells themselves appeared enlarged with more prominent nuclei. This hypertrophy was confirmed by electron microscopy, which also revealed that the type I cells contained an increased number of mitochondria, enlarged dense-cored vesicles, and markedly expanded rough endoplasmic reticulum. The morphological and ultrastructural changes seen in the CP mouse carotid body are strikingly similar to those observed in animals exposed to chronic hypoxia. Our study demonstrates that the HIF pathway plays a major role, not only in regulating both euoxic ventilatory control and the sensitivity of the response to hypoxia, but also in determining the morphology of the carotid body.

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Characteristics of carotid body chemosensitivity in NADPH oxidase-deficient mice

AJP Cell Physiology ◽

10.1152/ajpcell.2002.282.1.c27 ◽

2002 ◽

Vol 282 (1) ◽

pp. C27-C33 ◽

Cited By ~ 58

Author(s):

L. He ◽

J. Chen ◽

B. Dinger ◽

K. Sanders ◽

K. Sundar ◽

...

Keyword(s):

Tyrosine Hydroxylase ◽

Nadph Oxidase ◽

Carotid Body ◽

Gene Knockout ◽

Type I ◽

Type I Cells ◽

Carotid Bodies ◽

Marker Antigen ◽

I Cells

Various heme-containing proteins have been proposed as primary molecular O2 sensors for hypoxia-sensitive type I cells in the mammalian carotid body. One set of data in particular supports the involvement of a cytochrome b NADPH oxidase that is commonly found in neutrophils. Subunits of this enzyme have been immunocytochemically localized in type I cells, and diphenyleneiodonium, an inhibitor of the oxidase, increases carotid body chemoreceptor activity. The present study evaluated immunocytochemical and functional properties of carotid bodies from normal mice and from mice with a disrupted gp91 phagocytic oxidase (gp91 phox ) DNA sequence gene knockout (KO), a gene that codes for a subunit of the neutrophilic form of NADPH oxidase. Immunostaining for tyrosine hydroxylase, a signature marker antigen for type I cells, was found in groups or lobules of cells displaying morphological features typical of the O2-sensitive cells in other species, and the incidence of tyrosine hydroxylase-immunopositive cells was similar in carotid bodies from both strains of mice. Studies of whole cell K+currents also revealed identical current-voltage relationships and current depression by hypoxia in type I cells dissociated from normal vs. KO animals. Likewise, hypoxia-evoked increases in intracellular Ca2+ concentration were not significantly different for normal and KO type I cells. The whole organ response to hypoxia was evaluated in recordings of carotid sinus nerve activity in vitro. In these experiments, responses elicited by hypoxia and by the classic chemoreceptor stimulant nicotine were also indistinguishable in normal vs. KO preparations. Our data demonstrate that carotid body function remains intact after sequence disruption of the gp91 phox gene. These findings are not in accord with the hypothesis that the phagocytic form of NADPH oxidase acts as a primary O2 sensor in arterial chemoreception.

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Immunohistochemical Characteristics of the Human Carotid Body in the Antenatal and Postnatal Periods of Development

International Journal of Molecular Sciences ◽

10.3390/ijms22158222 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8222

Author(s):

Dmitry Otlyga ◽

Ekaterina Tsvetkova ◽

Olga Junemann ◽

Sergey Saveliev

Keyword(s):

Tyrosine Hydroxylase ◽

Carotid Body ◽

Nerve Fibers ◽

Individual Development ◽

Endocrine Function ◽

Type I ◽

Type I Cells ◽

Carotid Bodies ◽

I Cells ◽

Human Carotid

The evolutionary and ontogenetic development of the carotid body is still understudied. Research aimed at studying the comparative morphology of the organ at different periods in the individual development of various animal species should play a crucial role in understanding the physiology of the carotid body. However, despite more than two centuries of study, the human carotid body remains poorly understood. There are many knowledge gaps in particular related to the antenatal development of this structure. The aim of our work is to study the morphological and immunohistochemical characteristics of the human carotid body in the antenatal and postnatal periods of development. We investigated the human carotid bodies from 1 embryo, 20 fetuses and 13 adults of different ages using samples obtained at autopsy. Immunohistochemistry revealed expression of βIII-tubulin and tyrosine hydroxylase in the type I cells and nerve fibers at all periods of ontogenesis; synaptophysin and PGP9.5 in the type I cells in some of the antenatal cases and all of the postnatal cases; 200 kDa neurofilaments in nerve fibers in some of the antenatal cases and all of the postnatal cases; and GFAP and S100 in the type II cells and Schwann cells in some of the antenatal cases and all of the postnatal cases. A high level of tyrosine hydroxylase in the type I cells was a distinctive feature of the antenatal carotid bodies. On the contrary, in the type I cells of adults, the expression of tyrosine hydroxylase was significantly lower. Our data suggest that the human carotid body may perform an endocrine function in the antenatal period, while in the postnatal period of development, it loses this function and becomes a chemosensory organ.

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