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Biomedical subjects

A Mokashi

Publications and source records attributed to A Mokashi.

At least 73 records · Page 4Linked to original sources
PubMed1993

CO reveals dual mechanisms of O2 chemoreception in the cat carotid body.

The hypothesis that CO-binding pigments in the carotid body participate in O2 chemoreception was tested. The chemosensory nerve discharges of cat carotid body perfused and superfused in vitro at 36-37 degrees C with cell-free solution containing CO2-HCO3- (pH approximately equal to 7.39) were recorded to monitor O2 chemoreception. Several levels of PCO (60-550 Torr) at two levels of PO2 (50 Torr-140 Torr) were used. With high PCO of 500-550 Torr at any PO2 the discharge rate peaked promptly but the effect was significantly less than that to hypoxia. At any stage of the CO effect, exposure to light promptly attenuated or eliminated the response, as if the stimulatory effect of hypoxia was absent. Lower PCO of 60-70 Torr attenuated the response to hypoxia which was not suppressed by light. PCO of 140 Torr also attenuated the response to hypoxia and made the activity partially photolabile. During high PCO exposure the excitatory response to cyanide but not to nicotine was attenuated, consistent with the idea that the effects of nicotine are downstream from those of CO. Both inhibitory and excitatory effects of CO were promptly reversible. The results indicate that two types of CO-binding chromophores participate in O2 chemoreception in the carotid body.

Animals↗
PubMed1993

Dynamics of carotid body responses in vitro in the presence of CO2-HCO3-: role of carbonic anhydrase.

The role of carbonic anhydrase (CNA) in the dynamics of carotid body (CB) function was tested by studying the effects of the membrane-permeable CNA inhibitor methazolamide on the chemosensory responses of the cat CB, perfused and superfused in vitro with cell-free and modified Tyrode solution at 36.5 +/- 0.5 degrees C in the presence of CO2-HCO3- (PO2 = 120 Torr, PCO2 = 32 Torr, pH = 7.40). The bulk of CO2 flow to the CB from the external milieu was overwhelmingly large relative to the metabolic production of CO2 in the CB. Accordingly, the relative contribution of the endogenous CO2 to the CB responses was small. The chemosensory nerve discharges were recorded from the whole desheathed carotid sinus nerve. The responses to acidic hypercapnia (PCO2 = 50-60 Torr, pH = 7.20-7.10), hypoxia (PO2 = 25 and 50 Torr), perfusate flow interruption, and bolus injections of sodium cyanide (20-40 nmol) were tested. To contrast, we also measured the effects of nicotine (2-4 nmol), which may act at sites other than those for O2 and CO2. Methazolamide (30 mg/l) in the perfusate at constant PCO2 and pH reduced the baseline activity and delayed the responses to step changes in PCO2 (and concomitantly pH) and PO2 and to cyanide but not to nicotine. The steady-state responses to these stimuli, measured as differences from control, were reduced, but not significantly. The initial overshoots seen with step changes in both high PCO2 and low PO2 were eliminated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Aortic and carotid body chemoreception in prolonged hyperoxia in the cat.

Carotid body chemosensory response to hypoxia is attenuated as a result of prolonged normobaric hyperoxia (NH) in the cat. The effect of NH is likely to be due to high cellular PO2 and O2-related free radicals. Accordingly, the effect would be less if O2 delivery to the chemoreceptor tissue could be compromised. The aortic bodies, which appear to have less of a circulatory O2 delivery, as suggested by their vigorous responses to a slight compromise of O2 flow compared with those of the carotid body, could provide a suitable testing material for the hypothesis. We tested the hypothesis by studying both aortic and carotid body chemoreceptors in the same cats (n = 6) which were exposed to nearly 100% O2 for about 60 h. These chemoreceptor organs were also studied in 6 control cats which were maintained in room air at sea-level. The cats were anesthetized and their carotid and aortic chemosensory fibers were identified by the usual procedure, and their responses to hypoxia and hypercapnia and to bolus injections (i.v.) of cyanide and nicotine were measured. In the NH cats, the carotid but not aortic chemosensory responses to hypoxia and cyanide were attenuated and to hypercapnia (both onset and steady state) augmented. The aortic chemoreceptors were stimulated by hypoxia, hypercapnia, cyanide and nicotine both in the NH and the control cats similarly. The results support the hypothesis that it is presumably a higher tissue blood flow and hence a higher concentration of O2-related free radicals which ultimately led to the specific attenuation of O2 chemoreception in the carotid body.

Analysis of Variance↗
PubMed1991

Carotid chemosensory timing effects on cervical sympathetic discharges in the cat.

The hypothesis that respiratory phase-related sympathetic nerve activity would manifest timing effect of carotid chemosensory input with respect to the central respiratory drive was tested in the anesthetized, paralyzed and artificially ventilated cats which were also vagotomized and tracheostomized. Preganglionic cervical sympathetic nerve fibers (PSNF) which were clearly responsive to carotid chemosensory stimulation were selected for the test. Simultaneously with the PSNF, phrenic nerve (PN) and internal intercostal expiratory nerve (IICEN) activities were also recorded. In most instances, carotid chemosensory discharges were monitored in order to register the precise timing of its input to the brain-stem. Timed stimulation of carotid chemoreceptors was elicited by bolus injections of cyanide (10-20 micrograms), nicotine (10-20 micrograms) and CO2-saturated saline (0.2-0.5 ml) into the base of the common carotid artery. Two types of PSNFs were identified: type I discharged only in synchrony with the PN activity (13/47) and type II fired independently of, but entrained to, PN activity (34/47). Type I displayed characteristic timing effects of carotid chemoreflex on PN discharges. However, the sympathetic activity did not share the after-discharge of PN which persisted beyond the carotid chemoreceptor stimulation. Type II did not manifest any timing effect of carotid chemoreflex with respect to PN and IICEN activities. These results suggest the following model of carotid chemoreflex effects on sympathetic neuron activities: a group is exclusively gated by the properties of central respiratory drive whereas the other is not gated but entrained by it in the spontaneously breathing anesthetized cat.

Anesthesia↗
PubMed1991

Carbonic anhydrase and chemoreception in the cat carotid body.

To test the hypothesis that CO2 and O2 chemoreception in the carotid body (CB) may depend on its carbonic anhydrase (CA) activity, we used an in vitro cat CB preparation and studied the effects of methazolamide, a permeable CA inhibitor (pK 7.3), on the chemosensory responses to CO2, O2, and nicotine. The isolated CB was perfused and superfused with Tyrode solution, free of CO2-HCO3-, at 36.0 +/- 0.5 degrees C. The frequency of chemosensory discharges was recorded from the whole carotid sinus nerve. The responses to bolus injections (0.3-0.5 ml) of Tyrode solution equilibrated with PCO2 of 38-110 Torr, switching from HEPES to CO2-HCO3- Tyrode (PCO2 = 25-60 Torr) for about 3 min, hypoxic Tyrode (PO2 = 25-30 Torr) for 2-8 min, perfusate flow interruptions for approximately 4 min, and bolus injections of nicotine (4 nmol) were studied before, during, and after perfusion (30-45 min) with methazolamide (42.4 microM). Methazolamide reversibly inhibited, delayed, and reduced the responses to transient CO2 stimulus, diminished the onset of but not the late response to prolonged CO2 stimulus, and delayed but did not decrease the responses to hypoxia and perfusate interruption. The response to nicotine did not change. The results indicated that CA in the glomus cells played a crucial role primarily in the speed and magnitude of the initial response to CO2 stimulus and indirectly influenced O2 chemoreception. These effects were upstream from the nicotine receptor-mediated sensory response.

Animals↗
PubMed1991

In vitro perfused-superfused cat carotid body for physiological and pharmacological studies.

An in vitro perfused carotid body preparation was developed to study its chemosensory responses to physiological and pharmacological stimuli. The carotid bifurcation with the carotid body was vascularly isolated and excised from pentobarbital sodium-anesthetized cats. The CB was perfused in a chamber by gravity (80 Torr) with modified Tyrode's solution (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-NaOH at pH 7.40) equilibrated at a given Po2 and superfused with the same medium at (Po2 of 20 Torr). The temperature was maintained at 35.5 +/- 0.5 degrees C. The frequency of chemosensory discharges (CD) was recorded from the whole carotid sinus nerve (n = 24), and the responses were tested by repeated interruptions of perfusate flow (SF), perfusion with hypoxic medium, and injections of nicotine and cyanide (0.1 nmol to 1 mumol) and hypercapnic medium. During hyperoxic perfusion, SF resulted in a sigmoidal increase in CD, reaching a maximum that was 23.6 +/- 4.4-fold greater than the basal activity. Restoration of flow returned CD promptly to basal values. After normoxic perfusion, SF led to a similar maximal activity more rapidly, but the duration was shorter. Reduction of the perfusate PO2 (Po2 from 450 Torr to 150, 30, and less than 10 Torr) caused a nonlinear increase in CD. CO2 stimuli (PCo2 38-110 Torr) resulted in a linear increase in CD. Nicotine or cyanide increased CD in a dose-dependent manner. The preparation retained its initial responsiveness for 2-3 h, making extensive experimental studies feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Chemical respiratory control in chronically hyperoxic cats.

Chemical control of respiration in cats after chronic normobaric hyperoxia (NH; inhalation of 100% O2 for 60-67 h) was compared with that of control rats, anesthetized with pentobarbital. After chronic hyperoxia, induction of moderate hypoxia (PaO2 = 50-60 Torr) increased inspiratory time (TI) often without increasing tidal volume (VT). More intense hypoxia (PaO2 = 40-50 Torr) depressed tidal volume and further increased TI, diminishing the respiratory drive (VT/TI). Hypercapnia, on the other hand, increased tidal volume and shortened respiratory cycle time; but these responses were subnormal. The normal stimulatory effects of intravenous nicotine and inhibitory effect of dopamine on carotid chemo-receptor activity and ventilation were preserved in the NH cats. Cyanide, however, did not stimulate carotid chemoreceptor activity and ventilation. Thus, the changes in the carotid and aortic chemosensory activities elicited appropriate reflex ventilation responses, indicating that the central component of the chemoreflex was not impaired. The ventilatory depression during hypoxia despite an active chemosensory input is consistent with the lack of carotid chemosensory response to and a central depressant effect of hypoxia in the NH cats, and was presumably associated in part with an increased responsiveness of airway reflexes. We conclude that chronic hyperoxia selectively attenuated carotid chemosensory and chemoreflex responses to hypoxia.

Animals↗
PubMed1990

Cobalt stimulates carotid body chemoreceptors.

Because cobalt administration is known to elicit erythropoietin response, it is a reasonable hypothesis that cobalt would also stimulate the O2-sensing process in the peripheral chemoreceptors. We tested this hypothesis by measuring the effects of cobalt chloride on carotid chemosensory fibers in pentobarbital-anesthetized cats that were paralyzed and artificially ventilated. Responses of carotid chemoreceptor afferents to graded doses of cobalt given by intra-arterial injections (0.08-2.10 mumols) were measured at constant blood gases. Responses of the same chemoreceptor afferents to hypoxia, before and after a saturation dose of cobalt, were measured. In two experiments carotid body tissue PO2 was also simultaneously measured. The chemosensory fibers showed prolonged excitation after a brief period of inhibition subsequent to cobalt administration. The stimulatory effect showed a dose-dependent saturation response. Cobalt augmented rather than blocked carotid chemoreceptor response to hypoxia. The effect of cobalt was not mediated by tissue PO2. These results are consistent with the hypothesis that cobalt stimulates the O2-sensing mechanism, although a direct effect of cobalt on the excitability of the chemosensory terminal remains a possibility.

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

Peripheral and central dopamine receptors in respiratory control.

The role of peripheral and central dopaminergic mechanisms in respiratory control was studied in anesthetized cats. In one series, we simultaneously measured carotid chemoreceptor and ventilatory responses to hypoxia and hypercapnia before and after a saturation dose of intravenous domperidone, a peripheral dopamine (D2) receptor antagonist. Both carotid chemoreceptor and ventilatory responses were augmented by domperidone essentially in proportion, suggesting that they reflected the increase of peripheral chemoreceptor activity. Haloperidol which crosses into the brain from blood, given subsequent to domperidone, did not further affect carotid chemoreceptor responses but attenuated ventilatory responses to hypoxia without significantly altering those to hypercapnia. Thus, the additional ventilatory effect of haloperidol is mediated through central dopaminergic mechanisms involving peripheral chemoreflex pathway alone. In another series, the anesthetized cats were paralyzed and artificially ventilated to study carotid chemoreceptor responses to step increases in the end-tidal PCO2 before and after domperidone. Domperidone significantly augmented the responses to CO2. The results support the hypothesis that both peripheral and central dopaminergic mechanisms play a significant modulatory role in chemoreflex respiratory control.

Animals↗
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 inhalation and carotid body catecholamines: testing of hypotheses.

The purpose of this study was twofold: one concerns carotid blood flow and tissue PO2 and the other the effect of chronic hypoxic hypoxia on enhanced catecholamine content. The rationale was that chronic CO inhalation would not mimic the effect of hypoxia on the carotid body if its tissue blood flow is sufficiently high to counteract the effect of CO on O2 delivery and, hence, on tissue PO2. The differential effects of CO on the carotid body and erythropoietin-producing tissue would also indicate that the effect of hypoxic hypoxia on the carotid body is the result of a direct action of a local low O2 stimulus rather than secondary to a systemic effect initiated by other O2-sensing tissues. To test these alternatives we studied the effects of chronic CO inhalation on carotid body catecholamine content and hematocrit in the rats, which were exposed to an inspired PCO of 0.4-0.5 Torr at an inspired PO2 of approximately 150 Torr for 22 days. The hematocrit of CO-exposed rats was 75 +/- 1.1% compared with 48 +/- 0.7% in controls. Dopamine and norepinephrine content of the carotid bodies (per pair) was 5.88 +/- 0.91 and 3.02 +/- 0.19 ng, respectively, in the CO-exposed rats compared with 6.20 +/- 1.0 and 3.29 +/- 0.6 ng, respectively, in the controls. Protein content of the carotid bodies (per pair) was 18.4 +/- 1.6 and 20.5 +/- 0.9 micrograms, respectively. Thus, despite a vigorous erythropoietic response, the CO-exposed rats failed to show any significant stimulation of carotid body in terms of the content of either catecholamine or protein. The results suggest that carotid body tissue PO2 is not compromised by moderate carboxyhemoglobinemia because of its high tissue blood flow and that the chronic effect of hypoxic hypoxia on carotid body is direct.

Administration, Inhalation↗
PubMed1989

Effects of acute hyperbaric oxygenation on respiratory control in cats.

We studied ventilatory responsiveness to hypoxia and hypercapnia in anesthetized cats before and after exposure to 5 atmospheres absolute O2 for 90-135 min. The acute hyperbaric oxygenation (HBO) was terminated at the onset of slow labored breathing. Tracheal airflow, inspiratory (TI) and expiratory (TE) times, inspiratory tidal volume (VT), end-tidal PO2 and PCO2, and arterial blood pressure were recorded simultaneously before and after HBO. Steady-state ventilation (VI at three arterial PO2 (PaO2) levels of approximately 99, 67, and 47 Torr at a maintained arterial PCO2 (PaCO2, 28 Torr) was measured for the hypoxic response. Ventilation at three steady-state PaCO2 levels of approximately 27, 36, and 46 Torr during hyperoxia (PaO2 450 Torr) gave a hypercapnic response. Both chemical stimuli significantly stimulated VT, breathing frequency, and VI before and after HBO. VT, TI, and TE at a given stimulus were significantly greater after HBO without a significant change in VT/TI. The breathing pattern, however, was abnormal after HBO, often showing inspiratory apneusis. Bilateral vagotomy diminished apneusis and further prolonged TI and TE and increased VT. Thus a part of the respiratory effects of HBO is due to pulmonary mechanoreflex changes.

Animals↗
PubMed1988

Carotid body chemoreceptor and ventilatory responses to sustained hypoxia and hypercapnia in the cat.

To understand the role of carotid chemoreceptor activity in the ventilatory responses to sustained hypoxia (30 min) the following measurements were made in cats anesthetized with alpha-chloralose: (1) carotid chemoreceptor and ventilatory responses to isocapnic hypoxia and to hypercapnia during hyperoxia; (2) carotid chemoreceptor responses to isocapnic hypoxia after dopamine receptor blockade; and (3) ventilatory responses to hypoxia after bilateral section of carotid sinus nerves (CSN). Transition to hypoxia (PaO2 approximately equal to 52 Torr) from hyperoxia gradually increased carotid chemoreceptor activity by ten fold and ventilation by two fold without any detectable overshoot. Termination of isocapnic hypoxia with hyperoxia (PaO2 greater than 300 Torr) at 30 min promptly restored the carotid chemoreceptor activity to prehypoxic level. Ventilation also decreased promptly, but remained above the control value. Induction of hypercapnia (from 31.8 Torr to 43.9 Torr) during hyperoxia was followed by a prompt increase in the chemoreceptor activity by four fold which subsequently diminished, and by a gradual four fold increase in ventilation. Termination of hypercapnia after 30 min was followed by a prompt return of chemoreceptor activity and by a slow return of ventilation to near control levels. Dopamine receptor blockade increased carotid chemoreceptor responsiveness to acute hypoxia but did not alter the response pattern during sustained hypoxia. After bilateral CSN section, ventilation decreased during maintained hypoxia. Thus, a stimulatory peripheral and inhibitory central effects of hypoxia could produce a biphasic ventilatory response to short-term hypoxia in the anesthetized cat with intact CSN but did not manifest it. The results suggest that the chemosensory input not only promptly stimulates ventilation but also prevents the subsequent depressant effect of hypoxia on the brain-stem respiratory mechanisms and hence presumably a biphasic ventilatory response in the anesthetized cat.

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↗
PubMed1987

Ganglioglomerular nerves respond to moderate hypoxia independent of peripheral chemoreceptors in the cat.

The responses of the ganglioglomerular nerve (GGN) to transient changes and steady-state levels of paO2 at a constant paCO2 were studied in 12 anesthetized and spontaneously breathing cats before and after bilateral section of aortic (AN) and carotid sinus nerves (CSN). In two of these cats carotid chemoreceptor activity was monitored simultaneously. Onset of moderate hypoxia, down to paO2 of about 50 Torr, stimulated GGN activity and withdrawal of the hypoxic stimulus promptly eliminated the responses both before and after CSN section. CSN section, however, significantly raised the baseline activity and slightly delayed the GGN response to the onset of hypoxia. These responses to hypoxia are qualitatively similar to the characteristic responses of peripheral chemoreceptors. Thus, the basic oxygen chemosensing mechanism appeared to be present in the sympathetic nervous system, and is expressed in the postganglionic GGN activity. This property allows the sympathetic nervous system to perform physiologically important functions independent of the peripheral chemoreceptors.

Animals↗
PubMed1987

Cervical preganglionic sympathetic nerve activity and chemoreflexes in the cat.

The role of chemoreflexes originating from carotid body and central chemoreceptors in the regulation of cervical preganglionic sympathetic nerve (PSN) activity was studied in anesthetized and spontaneously breathing cats. PSN efferents which responded to hypoxia were selected for the study. The PSN activity, breath-by-breath inspiratory tidal volume, tracheal PO2 and PCO2, and arterial systemic blood pressure were recorded simultaneously. The responses of PSN efferents to transient changes in and steady-state levels of arterial PO2 and PCO2 and to graded bolus injections of intravenous sodium cyanide (50-100 micrograms), nicotine (50-100 micrograms), and dopamine hydrochloride (30-60 micrograms) were compared before and after bilateral section of carotid sinus nerves (CSN). CSN section raised the base-line PSN activity and practically eliminated the responses to brief pharmacological stimuli, but it did not eliminate the responses to transient changes in and steady-state levels of arterial PO2 and PCO2. However, CSN section diminished PSN responses and abolished ventilatory responses to hypoxia. Thus the PSN response to hypoxia was partly independent of peripheral chemoreflex and of respiratory drive. We conclude that carotid body chemoreflex elicits fast PSN responses and that a moderate decline in arterial PO2 causes an additional slow, direct excitation of sympathetic nervous system. The latter indicates O2 chemosensitivity of the system in the physiological range of arterial PO2. This O2-sensing property may allow sympathetic nervous system to initiate chemoreflex responses independent of the peripheral chemoreceptors.

Animals↗