Biomedical subjects

A K Sherpa

Publications and source records attributed to A K Sherpa.

5 recordsLinked to original sources

PubMed1993

Hyperbaric oxygenation alters carotid body ultrastructure and function.

We previously demonstrated that chronic normobaric hyperoxia (NH) for 60-67 h attenuated the carotid chemosensory response to hypoxia, probably initiated by the generation of reactive oxygen species (ROS). Since biological systems are affected by oxygen in a dose-dependent manner, we hypothesized that hyperbaric oxygenation (HBO) would affect the cellular mechanisms of oxygen chemoreception in a shorter time. To test the hypothesis, we studied the effects of oxygen at 5 atmospheres absolute (ATA) on cats (n = 7) carotid body ultrastructure and chemosensory responses to hypoxia, hypercapnia, and to bolus injections of cyanide, nicotine and dopamine. Four control cats breathed room air at 1 ATA. At the termination of the experiments, carotid bodies from 4 cats in each group were fixed and prepared for electron microscopy and morphometry. On the average, HBO diminished the chemosensory responsiveness to hypoxia (P < 0.01, unpaired t-test) within about 2 h, supporting the hypothesis. The responses to hypercapnia or bolus injections of cyanide, nicotine and dopamine were normal. HBO did not diminish the distribution of the dense-cored vesicles but significantly increased the mean volume-density of mitochondria and decreased the cristated area per mitochondrion in the glomus cells. The latter suggests a link between oxidative metabolism and chemosensing, and the former excludes availability of neurotransmitters being the cause of the blunted chemosensory response to hypoxia.

Animals↗

PubMed1989

Sympathetic peripheral chemoreflex is independent of expiratory output neurons in the cat.

Previously we reported that activities of certain chemoreflex sensitive cervical preganglionic sympathetic nerves (PSN) were augmented by carotid chemoreceptor stimulation independently of phrenic nerve (PN) activity in the cat. To test the hypothesis that the PSN carotid chemoreflex could have been mediated by the expiratory neuron activity, we studied the relationship between PSN, internal intercostal expiratory nerve (IICEN) and PN activities in vagotomized, anesthetized, paralysed and artificially ventilated cats. We made the following observations. (1) Hypoxia often inhibited IICEN activity while the PN and PSN activities were stimulated. (2) during normoxia, cyanide strongly stimulated PN and PSN discharges but only moderately IICEN discharges. (3) Hyperventilation hypocapnia suppressed or eliminated PSN and PN rhythms and activities, but made some IICEN fibers fire continuously. (4) During hypocapnic apnea, cyanide stimulated PSN activity before PN and IICEN activities, although some PSN fibers were stimulated simultaneously with PN fibers. Accordingly we conclude that IICEN activity does not significantly influence chemoreflex stimulation of PSN activity and that a direct chemoreflex stimulation of IICEN is minimal in the cat. Thus, the chemoreflex PSN response is in part independent of respiratory chemoreflex pathways.

Action Potentials↗

PubMed1989

Stimulus interaction between CO2 and almitrine in the cat carotid chemoreceptors.

The hypothesis that augmentation of the carotid chemoreceptor response to hypoxia by almitrine is due in part to an increased response to CO2 was tested by using single or few fiber preparation of carotid body chemosensory fibers in 12 cats anesthetized with alpha-chloralose. To differentiate between the plausible mechanisms of effects, we also tested the responsiveness of the afferents to cyanide and nicotine before and after almitrine. After a saturation dose of almitrine (1 mg.kg-1 followed by 0.5 mg.kg-1.h-1) the chemosensory responses to CO2 strikingly increased even during hyperoxia: the afferents showing an increased transient peak activity at the onset of hypercapnia, an augmented steady-state response to CO2 stimulus, and a decreased arterial PCO2 stimulus threshold. Thus, the effect of almitrine on carotid chemoreceptor response to hypoxia could be explained, at least in part, by its multiplicative stimulus interaction with CO2. After almitrine, the chemoreceptor response to cyanide, which is dependent on arterial PO2, was not particularly augmented relative to those of nicotine. Accordingly, the O2-sensing mechanism does not appear to be the primary site of almitrine effect. The results also indicate that the site of CO2 chemoreception resides downstream from those of hypoxia.

Almitrine↗

PubMed1989

Chronic CO exposure stimulates erythropoiesis but not glomus cell growth.

The effect of chronic CO exposure, which stimulates erythropoietin production and erythropoiesis, was studied on carotid body cells in the rat. The hypothesis to be tested was that chronic CO inhalation would stimulate cellular hypertrophy and hyperplasia of carotid body if it caused local tissue hypoxia as in chronic hypoxia. The failure of an appropriate response would indicate a lack of a specific local effect on carotid body tissue PO2 presumably because of its unusually high tissue blood flow. Six young male rats were exposed to 0.4-0.5 Torr (0.05-0.07%) inspired PCO in air for 22 days. Control rats (n = 6) were maintained under similar conditions except for CO exposure. After the exposure period the rats were anesthetized, blood was collected for hematocrit, and the carotid bodies were surgically exposed and fixed for electron microscopy and morphometry of type I and type II cells and capillary endothelium. Hematocrit was significantly greater in the CO-exposed group (75 vs. 48%), whereas no significant difference was found in the carotid body parenchyma between the control and CO-exposed groups. We conclude that the lack of an effect of chronic CO exposure on the carotid bodies in contrast to the strong erythropoietic response indicates a relatively high tissue blood flow rate in the carotid body and that CO did not exert a direct cellular effect. The results also suggest that the hypertrophic response of carotid body glomus cells to chronic hypoxic hypoxia is the result of a local direct effect of low PO2 rather than secondary to systemic effects.

Animals↗

PubMed1988

Relationship between sympathetic and phrenic nerve responses to peripheral chemoreflex in the cat.

To test the hypothesis that peripheral chemoreflex effect on the preganglionic cervical sympathetic nerve (PSN) activity is entirely mediated by the central respiratory drive (CRD), as expressed in the phrenic nerve (PN) activity, we studied the relationship between PN and PSN activities under controlled conditions of carotid chemosensory excitation in the anesthetized cats. The cats were vagotomized, paralyzed and artificially ventilated. Tracheal pO2 and pCO2, systemic blood pressure, activities of single or a few PSN and PN fibers and a PN bundle were simultaneously recorded. The PSN preparations, which were responsive to hypoxia and showed PN rhythm, were selected for the study. Carotid chemoreceptor excitation, produced by hypoxia (end-tidal pO2 approximately equal to 50 Torr) or by sodium cyanide injection (50-100 micrograms, i.v.), elicited 3 types of responses: (1) the PSN discharged during the silent period of PN activity, although the PSN peak activity was still coupled to the PN peak activity, (2) PSN discharged only during PN activity, and (3) during the absence of PN discharge induced by hyperventilation hypocapnia, cyanide injection stimulated the PSN without PN activity. These observations suggest a model of chemoreflex control of sympathetic nerve activity which consists of two parts: one is dependent on PN activity and the other is not. Accordingly, all PSN chemoreflex responses may not be integrated with all inspiratory chemoreflexes.

Animals↗