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Biomedical subjects

M Pokorski

Publications and source records attributed to M Pokorski.

At least 73 records · Page 4Linked to original sources
PubMed1983

Relative peripheral and central chemosensory responses to metabolic alkalosis.

We investigated the relative contribution of peripheral and central chemosensory mechanisms to ventilatory responses to metabolic alkalosis in anesthetized cats by simultaneously measuring steady-state carotid body chemosensory activity and ventilation. The effects of graded steady-state levels of metabolic alkalosis at constant levels of arterial O2 and CO2 partial pressure (PaO2 and PaCO2, respectively) were studied first. Then the responses to isocapnic hypoxia and hyperoxic hypercapnia before and after the induction of a given level of metabolic alkalosis were studied. From the relationship between the carotid chemosensory activity and ventilation, the contribution of the two chemosensory mechanisms was estimated. The depression of ventilation that could not be accounted for by a decrease in the carotid chemosensory activity is attributed to the central effect. We found that metabolic alkalosis decreased both carotid chemosensory activity and ventilation at all levels of PaO2 or PaCO2. The ventilatory effect of alkalosis increased during hypoxia due to suppression of both peripheral chemosensory input and its interaction with the central CO2-H+ drive. During hyperoxia the central effect of alkalosis was predominant, although the peripheral effect increased with hypercapnia. We conclude that acute metabolic alkalosis suppresses both peripheral and central chemosensory drives, and its ventilatory effect grows larger with decreasing PaO2.

Action Potentials↗
PubMed1983

Opposing effects of dopamine receptor blockade on ventilation and carotid chemoreceptor activity.

To determine the effects of dopamine receptor blockade on the ventilatory responses to hypoxia and hypercapnia we simultaneously measured ventilation and carotid chemoreceptor activity in eight anesthetized cats. During normoxia, haloperidol (1 mg . kg-1 iv) stimulated carotid chemoreceptor activity within 15 s of its administration from a control level of 5.3 +/- 1.1 to 10.4 +/- 2.0 impulses . s-1. Minute ventilation (VI) also rose from 1.00 +/- 0.20 to 1.66 +/- 0.34 l . min-1. Chemoreceptor activity remained elevated, but in the next 15 min VI fell back to or below control levels. Thus haloperidol produced a transient stimulation of ventilation. In the steady state, after haloperidol, carotid chemoreceptor activity was also elevated significantly at all levels of arterial O2 and CO2 partial pressures (PaO2 and PaCO2, respectively). Steady-state ventilation, however, was not significantly different in normoxia (PaO2 82 Torr) after haloperidol despite the elevated chemoreceptor activity. Haloperidol also greatly attenuated the ventilatory response to hypoxia, despite the stimulated carotid chemoreceptor activity. The ventilatory response to hypercapnia was not significantly affected by haloperidol, indicating that its effect was specific for the chemoreflex responses to hypoxia. We conclude that dopamine antagonism by haloperidol blocks the central integration of peripheral chemoreceptor activity, thus attenuating the ventilatory chemoreflex responses to hypoxia while augmenting the carotid chemoreceptor response.

Animals↗
PubMed1982

Arterial blood--spinal fluid oxygen gradient diminishes during alkalaemia in hyperoxic man.

We investigated the effect of intravenous sodium bicarbonate (2 mmol x kg-1) on the arterial blood-spinal fluid PO2 gradient in twelve anaesthetized hyperoxaemic human subjects who were in preparation for surgical procedures The steady-state samples of arterial blood and lumbar fluid were withdrawn for the assessment of the acid-base status and electrolyte content in both fluid compartments before and after NaHCO3 injection. We found that NaHCO3 increased the arterial pH and PCO2, and decreased the blood-spinal fluid PO2 gradient significantly. The latter was a result of an increase in spinal fluid PO2 and a decrease in PaO2. The diminished PO2 gradient can be accounted for by the specific effect of carbamate and bicarbonate, distinct from that of pH, lowering the affinity of haemoglobin for oxygen. This might favor the maintenance of an adequate oxygen supply in the brain tissue under unfavorable conditions.

Adult↗
PubMed1982

Inhibition of aortic chemoreceptor responses by metabolic alkalosis in the cat.

The responses of the same aortic chemoreceptor afferents to steady-state isocapnic hypoxia and to hypercapnia on hyperoxia, before and after the induction of metabolic alkalosis, were investigated in 12 anesthetized cats. Metabolic alkalosis was achieved by intravenous administration of sodium bicarbonate in the average dose of 7 mmol . kg-1. On the average, arterial pH (pHa) increased from 7.383 to 7.650 at an arterial CO2 partial pressure (PaCO2) of 30 Torr. The increase in pHa resulted in a decrease in chemoreceptor activity, the effect being greater at a lower arterial O2 partial pressure. Increases in PaCO2 during hyperoxia resulted in an increased activity of the chemoreceptors both before and after NaHCO3 injection. The stimulatory effect of hypercapnia, however, was attenuated by metabolic alkalosis. At a constant PaCO2, decreases in arterial [H+] by the NaHCO3 administration caused an approximately linear decrease in the chemoreceptor activity. At a constant arterial [H+], higher PaCO2 was associated with a slightly greater activity of the chemoreceptors. These results indicate that the major effect of CO2 is mediated by [H+], but there appears to be another mechanism, albeit small, for the effect of CO2.

Alkalosis↗
PubMed1981

Augmentation of carotid body chemoreceptor responses by isoproterenol in the cat.

The effects of intravenous injections of isoproterenol (0.5-2 microgram) on the responses of carotid body chemoreceptor afferents and on integrated phrenic activity were investigated in twelve anesthetized and three decerebrate, unanesthetized cats. All animals were paralyzed and artificially ventilated. Isoproterenol stimulated carotid chemoreceptor activity and this stimulation was augmented by both hypoxia and hypercapnia. Following an injection of isoproterenol, the ratio of the minute phrenic activity relative to mean carotid chemoreceptor activity was increased. Thus, the stimulation of inspiratory phrenic output exceeded the stimulation of the chemoreceptor afferent input, and the peripheral chemoreflex activity does not account for the entire ventilatory response. To distinguish between a direct effect of isoproterenol and a possible secondary effect mediated via an increased venous return and an increased PaCO2, the latencies of the response of carotid chemoreceptors to both isoproterenol and hypercapnia were compared before and after carbonic anhydrase inhibition by acetazolamide. After acetazolamide, the latency of the response to hypercapnia increased from 3.5 sec to 8 sec whereas the latency of response to isoproterenol increased less, from 4.7 sec to 6.3 sec. Thus, isoproterenol stimulation was not mediated by CO2-H+. Propanolol, which blocked the systemic vascular effect, only partially blocked the chemoreceptor stimulation caused by isoproterenol, indicting that the effect of isoproterenol on chemoreceptor activity was not due to systemic cardiovascular changes.

Acetazolamide↗
PubMed1981

Responses of aortic chemoreceptors before and after pneumothorax in the cat.

That the response of aortic chemoreceptors to hypercapnia is considerably smaller than that of carotid chemoreceptors is well accepted, but the mechanism for the difference is not known. It has been suggested that surgical exposure of the carotid body may contribute to the difference. Accordingly, the response of aortic body chemoreceptors to CO2 would be expected to resemble quantitatively that of carotid chemoreceptors after exposure of the aortic bodies by pneumothorax. The effect of opening the chest on aortic and carotid chemoreceptor responses to several levels of arterial CO2 and O2 tension and arterial blood pressure were studied in anesthetized cats. The activity of aortic chemoreceptors increased in spite of a decreased stimulus level in the thoracic cavity after pneumothorax. The activity remained higher than the control at all levels of arterial CO2 and O2 tension and arterial blood pressure. However, the slopes of CO2 response curves, which were initially small, did not change after pneumothorax. Thus a change in the normal environment of the aortic bodies by experimental manipulation did not cause the aortic chemoreceptor responses to resemble those of carotid chemoreceptors.

Animals↗
PubMed1981

Effects of naloxone on carotid body chemoreception and ventilation in the cat.

The effects of intravenous injection of naloxone (0.4 mg.kg-1), an opiate antagonist, on the responses of carotid body chemoreceptor discharge and ventilation to steady-state levels of hypoxia and hypercapnia were investigated in 12 anesthesized cats. After naloxone, carotid chemoreceptor response to hypoxia (PaO2 60--30 Torr) was enhanced, a finding that suggested that the endogenous enkephalin-like peptide present in the carotid body inhibits carotid chemoreceptors. This reasoning is supported by the observation that close intra-arterial injection of met-enkephalin inhibits carotid chemoreceptors and that the effect is blocked by naloxone. After naloxone, ventilation was stimulated even in the absence of a significant stimulation of carotid chemoreceptors during hyperoxia, indicating that ventilation is normally suppressed by endogenous opiates in the central nervous system, an effect disinhibited by naloxone. Also, the ventilatory effect of the peripheral chemoreceptor input was augmented after naloxone.

Animals↗
PubMed1976

Neurophysiological studies on central chemosensor in medullary ventrolateral areas.

Nonphasic unit potentials were recorded with glass microelectrodes from the ventrolateral medullary areas in spontaneously breathing cats. The firing rate changes were studied during metabolic acidosis and alkalosis induced by intravenous injections of 4 ml 0.1 N HCl and molar NaHCO3, respectively, and during CO2 rebreathing. Three groups of units were distinguished among 44 neurons: 1) 9 U were markedly sensitive to variations in acid-base parameters; each reacted in the opposite manner upon acidosis and alkalosis, and these reactions were reproducible. 2) Twelve units were responsive to touch of a contralateral limb with a prompt and massive rise in firing rate. 3) The remaining 23 U were classified as nonsensitive to any of the stimuli applied. All these 44 U were found to be intermingled. It is possible that the chemosensitive cells found may be part of the central chemosensor.

Action Potentials↗
PubMedDate not supplied

Ventilatory response to hypoxia in elderly women.

BACKGROUND: The respiratory system is subject to the ageing process, which could limit its responsiveness to stimuli. Attenuation of the ventilatory response to hypoxia in old age is, as yet, an unresolved issue. Such attenuation may be germane to the pathogenesis of hypoxic respiratory disorders developing more often in elderly subjects. AIM: The study seeks to determine the potential adverse effects of age on the hypoxic ventilatory response by comparing this response in groups of elderly and young female subjects. SUBJECTS AND METHODS: Nineteen healthy women of the mean age of 71+/-1.3 (SE) years and 16 women in their twenties were required to perform a progressive isocapnic hypoxic test, based on the rebreathing technique. The ventilatory response was evaluated from the slopes of minute ventilation and mouth occlusion pressure, an index of inspiratory neuromuscular drive, against arterial oxygen saturation. The breathing pattern components also were measured with the breath-by-breath routine. RESULTS: Ventilatory response to hypoxia averaged 0.65+/-0.10 L/min/% SaO(2) and neuromuscular output was 0.012+/-0.002 kPa/% SaO(2) in the elderly women and these slopes were not reduced compared with those in the young. Nor did the ventilatory slopes relate to age in the older subjects. Baseline breathing pattern was modified in the elderly in that the mean inspiratory flow was significantly higher, but it reached the same stimulated level as that in the young. CONCLUSIONS: Ventilatory response to hypoxia is independent of age in healthy women. Thus, functional sensitivity of the respiratory control mechanisms does not attenuate with age.

Adult↗
PubMedDate not supplied

Respiratory responses following lifting the legs in normal man.

This study reinvestigates the problems of ventilatory drive linked to the rate of CO2 flow to the pulmonary circulation, and the respiratory response to the changes in cardiac output, which are both known to be capable of matching ventilation to perfusion so that the arterial blood remains isocapnic. Taking advantage of the known influence of posture on venous return, 21 healthy humans were subjected to the experimental maneuver which consisted of lifting the legs from the lower to uppermost position. This maneuver increased venous return to the right heart by bringing stagnant blood from the legs carrying more CO2. In all, 34 tests were performed. The results showed a rapid increase in minute ventilation of 12.3 percent. There were also increases in end-tidal CO2, CO2 production and cardiac output. All of the changes were fully reversible and reproducible. The results support the concept that a higher gain CO2 receptor system is operating during increased CO2 delivery to the lungs via the circulation. The possibility of reflex hyperpnea elicited from pressoreceptors localized in pulmonary circulation is also considered.

Adult↗
PubMedDate not supplied

N-oleoyl-dopamine increases locomotor activity in the rat.

N-oleoyl-dopamine (OLDA), a condensation product of oleic acid and dopamine (DA), is a bioactive lipid whose biological functions are not yet fully explored. The compound crosses the blood-brain barrier and might be considered as a carrier of DA into the brain. In this study we sought to determine whether OLDA would influence locomotor behavior and whether the central DA system would be involved in such influence. We addressed this issue by investigating horizontal locomotor activity in male Wistar rats after intraperitoneal administration of OLDA, 5-20 mg/kg, before and after pre-treatment with haloperidol, a D2 receptor antagonist. We found that OLDA caused a prompt stimulation of locomotor activity, with a bell-shaped dose-response. The maximum stimulatory effect was observed after 10 mg/kg of OLDA where the mean distance traveled by rats during a 2-hour test increased to 1213+/-196(SE) cm from the 403+/-89 cm in the vehicle-treated rats (P<0.05). This effect was dose-dependently antagonized by haloperidol (0.1-0.2 mg/kg). The results support the hypothesis that the OLDA-induced hyperlocomotion was mediated by the stimulation of DA systems. Using in vitro assays, we further demonstrated that OLDA is a stable compound that resists hydrolysis over a 2-hour period and thus the integral OLDA compound exerted DA-like effects. We conclude that OLDA is a potential brain modifier of motor behavior, the biological consequences of which remain to be explored.

Animals↗
PubMedDate not supplied

Ascorbic acid enhances hypoxic ventilatory reactivity in elderly subjects.

The reducing properties of ascorbic acid in the carotid body make it a likely modifier of hypoxia-sensing mechanisms. This open-label study aimed to determine the effect of ascorbic acid on the hypoxic ventilatory response (HVR) in a population of elderly women, in whom both hypoxic reactivity and ascorbic acid levels may be deficient. We examined the HVR to progressive eucapnic hypoxia in 18 healthy females aged 60-80 years, before and after 10 days' ascorbic acid supplementation, given as a sustained release preparation of 1 g twice daily. Respiratory variables were recorded breath by breath, and hypoxic sensitivity was assessed from the linear slopes of minute ventilation and mouth occlusion pressure plotted against oxygen saturation. We found that ascorbic acid increased the HVR by a mean of 44%, this effect being driven by a higher occlusion pressure. We conclude that augmentation of hypoxic reactivity by ascorbic acid may have therapeutic potential in pathologies associated with hypoxia, which frequently develop in old age.

Aged↗
PubMedDate not supplied

Chemosensitive neurons on the ventral medullary surface.

Central chemosensitivity is ascribed to three areas on the ventral medullary surface. The discharge frequency of neurons observed in these areas depends upon pH. Other neurons within the same areas do not change their frequency during acidosis or alkalosis. Histologically the areas are characterized by superficial nerve cells.

Acidosis↗