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Biomedical subjects

M Pokorski

Publications and source records attributed to M Pokorski.

At least 19 recordsLinked to original sources
PubMed1998

Fatty acid acylation of dopamine in the carotid body.

In this article, we put forward a hypothesis concerning the assembling and storage of dopamine molecules in the dense-core vesicles of the carotid body chemoreceptor cell. We posit that dopamine molecules are packed and sustained in the vesicular form due to the formation of N-acyldopamine, a condensation product of fatty acid acyl chain and dopamine at the amino group of the latter. N-acyldopamine would then be stored in a micelle-like supramolecular structure formed due to self-association through the hydrophilic dopamine headgroups. This hypothesis may help explain the perennial problem of the role of dopamine in chemoception. It also draws attention to the possibility of the existence of neurotransmitters in the N-acylated form. This could lead to the design of acylated compounds that would play a role of prodrugs slow-releasing active substances by hydrolysis into the desired environment.

Acylation↗
PubMed1997

Hypoxia depletes ascorbate in the cat carotid body.

Vitamin C or L-ascorbate is an effective endogenous reducing agent influencing the functions that are involved with the redox mechanism. Detection of oxygen tension changes by the carotid body chemoreceptors is one such function. In this study we investigated the hypothesis that the level of ascorbate, if present, could change in the carotid body as a result of ascorbate's interaction in the chemosensing process, which would be reflected in the production of the ascorbyl radical. We addressed this issue by examining changes of the ascorbyl radical, using the in vitro electron spin resonance spectroscopy (ESR), in the carotid bodies dissected from pentobarbitone anesthetized cats exposed in vivo to three eucapnic, breathing gas mixtures of different O2 concentration: normoxic, 21% O2; hypoxic, 7% O2; and hypoxic-reoxygenated, 7% O2 followed by 100% O2. Each group consisted of five cats, yielding five pairs of carotid bodies for the ESR signal recording. We found that the intensity of ESR signals, measured as peak-to-peak amplitude, was diminished by 39 and 43% in the hypoxic and hypoxic-reoxygenated groups, respectively, compared with that in normoxia. The study shows that ascorbate was present in the normoxic carotid body and was depleted by hypoxia. We conclude that ascorbate is part of free radical mechanisms operative in the carotid body in hypoxia.

Animals↗
PubMed1997

Involvement of the motor trigeminal nucleus in respiratory phase-switching in the cat.

We investigated the hypothesis that the motor trigeminal nucleus, consisting of expiratory motoneurons, might be influential in termination of inspiration. We addressed the issue by comparing the effects on neural respiration of a reversible, unilateral, pharmacologic blockade of the motor trigeminal nucleus (5M), the medial parabrachial nucleus (PB), and of other nearby structures that are neutral for respiration in anesthetized, vagotomized, paralyzed, and ventilated cats. The blockade was achieved by microinjections of 2% xylocaine, laced with Pontamine Sky Blue to identify sites of injections, from the tip of a penetrating microelectrode. Integrated phrenic neurograms were recorded to quantify the time of neural inspiration (TI), expiration (TE), and the peak phrenic amplitude. We found that blockade of the 5M caused a pattern of apneustic respiration, consisting of a selective prolongation of inspiratory phases that were interrupted by short expiratory pauses. In contrast, blockade of the PB resulted in a prolongation of both TI and TE, which corresponds to a mere slowing of respiration. The results confirmed important functions of the rostral pons in ventilatory control but pointed to the 5M rather than PB as a structure underlying the inspiratory off-switch. We conclude that the motor trigeminal nucleus may have a part in the pontine pneumotaxic mechanism.

Animals↗
PubMed1997

ATP activates phospholipase C in the cat carotid body in vitro.

In this study we investigated the hypothesis that ATP could play a role in the transduction of the hypoxic stimulus in the carotid body (CB) by being a regulator of the phosphatidylinositol-4,5-bisphosphate (PIP2)-specific phospholipase C (PLC). We addressed this question by comparing the PLC activity in the absence and presence of ATP in homogenates of CBs dissected from anesthetized cats that were preexposed in vivo to the contrasting conditions of normoxia (PaO2 approximately 90 mmHg) and hypoxia (PaO2 approximately 20 mmHg). The tissue of a nearby superior cervical ganglion (SCG) was used as a reference. The homogenate was the source of PLC. PLC activity was assayed by measuring the formation of radioactive inositol 1,4,5-trisphosphate from [3H]PIP2, used as an exogenous substrate. ATP was added to the assay mixture at the concentrations of 0.25 mM and 1 mM, chosen on the basis of test trials on ATP dependence of PLC changes. We found that ATP increased appreciably the PLC activity over its basal (absence of ATP) level in the normoxic carotid body. The stimulatory effect of ATP was augmented in the hypoxic carotid body, the lower ATP concentration having a stronger effect. Such PLC changes were absent in the SCG. These findings suggest a regulatory role for ATP in the PLC-linked hypoxic signal transduction in the carotid body.

Adenosine Triphosphate↗
PubMed1997

[Diaphragmatic electromyogram and respiratory pattern after unilateral and bilateral partial denervation of the diaphragm in the cat].

In the present study we investigated the mechanism of early respiratory compensation of partial paralysis of the sternal and lateral diaphragm due to an unilateral or bilateral section of the C5 rootlet of the phrenic nerves in anesthetized cats. Compensatory effects were evaluated from the recordings of the bilateral diaphragmatic EMGs, neural respiratory pattern and ventilation. The results of the study demonstrate that successive C5 denervation of the diaphragm caused a decrease in the ipsilateral diaphragmatic EMG. Bilateral C5 section evoked an up to 10 percent decrease in minute ventilation. The compensation of the unilateral and then bilateral partial impairment of the muscle function was achieved always by an increase in the neuromuscular projection to the currently contralateral diaphragm. Neural mechanisms of compensation involve a general increase in the respiratory drive, expressed mostly as an increase in the frequency of breathing. The contribution of afferent respiratory muscles to these mechanisms is likely.

Animals↗
PubMed1997

Ultrastructural manifestation of pharmacologic inhibition of the activities of lipases and proteases in the cat carotid body.

This study is based on the premise that if a subcellular element of an organ performs an appreciable functional role, then its inhibition could influence the ultrastructural organization of the organ. We addressed this issue in the investigation on the carotid body, a chemosensory organ, by comparing the ultrastructure of its parenchyma in phenylmethylsulfonyl fluoride (PMSF)-injected cat with that of the normal cat. PMSF, an inhibitor of lipases and proteases, induced degenerative changes chiefly in subcellular components other than the neurosecretory and synaptic elements being associated with signal transduction. The study suggests that the inhibited enzymes might also have to do with the carotid body function.

Animals↗
PubMed1994

Endogenous benzodiazepine system and regulation of respiration in the cat.

Benzodiazepines, a class of drugs widely used as anxiolytics, can induce a depression of respiration. This study was designed to determine if endogenous benzodiazepine ligands could act in a similar fashion and exert a tonic inhibitory influence on respiration. Administration of a benzodiazepine antagonist should then facilitate respiration. This might be especially visible in hypoxia, the condition characterized by both central respiratory depression and potentially enhanced benzodiazepine expression. We addressed this issue by comparing the effects on the phrenic neurogram of the specific benzodiazepine antagonist flumazenil (200 micrograms i.v. boluses) in the contrasting conditions of hypoxia and hyperoxia in anesthetized, both spontaneously breathing and paralyzed ventilated cats. Contrary to our hypothesis, flumazenil showed a modest but definite inhibitory effect on respiration. Flumazenil also lengthened the duration of the Hering-Breuer inspiratory inhibition. The respiratory depression was neither related to chemical drive nor to the GABA receptor complex, for it was sustained after antagonism of GABA with picrotoxin and bicuculline. We conclude that the endogenous benzodiazepine system is unlikely to play an inhibitory role in the regulation of respiration. The physiologic role of this system remains to be established.

Animals↗
PubMed1991

Endogenous opiates and ventilatory acclimatization to chronic hypoxia in the cat.

The effects of the opiate antagonist naloxone (0.4 mg.kg-1, i.v.) on carotid chemoreceptor and ventilatory responses to graded steady-state levels of hypoxia and hypercapnia were investigated in two groups of cats: chronically normoxic and chronically hypoxic. The cats of the latter group were exposed to PIO2 of about 70 mm Hg at sea level for 3-4 weeks and showed an attenuated response to hypoxia. All cats were tested under alpha-chloralose anesthesia. Naloxone treatment did not increase appreciably carotid chemoreceptor activity or its responses to hypoxia and hypercapnia in either cat group. Naloxone caused a small ventilatory stimulation in the chronically hypoxic cats, so that the attenuated response to hypoxia was not relieved. By contrast, the chemoreflex ventilatory response to hypoxia was stimulated by naloxone in the chronically normoxic cats. The findings that the depressed ventilatory chemoreflexes in the chronically hypoxic cat were not ameliorated by the opiate antagonist indicate that an increased elaboration of endogenous opiates does not underlie ventilatory adaptation to chronic hypoxia.

Acclimatization↗
PubMed1991

Cardiorespiratory reactions to static, isometric exercise in man.

Cardiac output (Q), stroke volume (SV), heart rate (HR), and respiratory variables were measured in ten healthy men performing static, isometric muscular contraction (handgrip) during air breathing. We found an instantaneous rise in ventilation (VI) and in HR, accompanied by a minimal rise in cardiac output. The rise in VI was due to a rise in tidal volume (VT) and a reduction in expiratory duration (TE). These effects of isometric exercise are explainable as due to a muscle reflex instantly inhibiting the cardiac, vagal motoneurons and, at the same time, stimulating neurons in the respiratory area of the medulla. These medullary neurons seem capable of independent operation. The rise in mean arterial pressure (MAP) during isometric exercise is 27% just as the rise in total peripheral vascular resistance (TPVR). The MAP rise is too high to be caused by vascular occlusion due to the high tension of contracted muscles in only one upper extremity. Thus, redistribution of Q in the system of many parallel vascular resistances is a likely possibility--with possible cutaneous vasodilation and dominating vasoconstriction of other vascular regions.

Adult↗
PubMed1990

Ventilatory and cardiovascular responses to hypoxic and hyperoxic static handgrip exercise in man.

The purpose of this study was to evaluate the ventilatory and cardiovascular responses to static handgrip exercise at different levels of arterial chemoreceptor activation. The study was done on 10 healthy subjects. They performed handgrip of 50% of maximal voluntary contraction on a background of either hypoxia (PE'O2 approximately 47 mm Hg) or hyperoxia (PE'O2 approximately 216 mm Hg), i.e., enhanced or suppressed chemoreceptor activity. The subjects were able to sustain the handgrip for 50-60 sec, during which time no steady-state responses were attainable. Minute ventilation (VI), cardiac output (Q), heart rate (HR), and a number of other variables were recorded. Handgrip exercise resulted in a rapid initial VI rise followed by a subsequent slow increase. Hyperoxia diminished the VI response over the exercise range. The ventilatory response was associated with an HR acceleration, increased arterial pressure and peripheral vascular resistance. No appreciable changes in Q were noted, nor was there any particular relationship between ventilatory and circulatory changes. These results provide no support for the Q mediated ventilatory stimulus during static handgrip exercise in man. It is concluded that the ventilatory and cardiovascular responses are of independent nature.

Cardiac Output↗
PubMed1990

Cardiac responses to hypoxia and hypercapnia in spinal man.

The purpose of this study was to evaluate the effect of interruption of the descending supraspinal sympathetic outflow on heart rate control during exposures to chemical stimuli. We investigated the heart rate responses to progressive isocapnic hypoxia and hyperoxic hypercapnia using the rebreathing technique and quantified the relationship between heart rate (HR), oxygen saturation (SaO2), alveolar PCO2 (PACO2), and minute ventilation (VE) in 16 chronic tetraplegic subjects with low cervical spinal cord transection. The HR responses were determined from the linear slopes of HR on SaO2 and HR on PACO2. We found that mean resting heart rate was within normal range; 66 +/- 3 (SEM) beats min-1. HR increased as oxygenation fell or CO2 tension rose. The mean tetraplegic delta HR/delta SaO2 was 0.83 +/- 0.14 beats min-1 per 1% fall in SaO2 and that of delta HR/delta PACO2 was 0.30 +/- 0.13 beats min-1 per mmHG rise in PACO2. The HR and VE responses to either hypoxia or hypercapnia were related in the tetraplegic subjects. We conclude that the stimulatory HR responses to chemical stimuli are not suppressed by cervical spinal cord transection. Thus, the descending sympathetic activity does not underlie the HR acceleration by chemical stimuli.

Adolescent↗
PubMed1990

Cardiac output and heart rate in man during simulated swimming while breath-holding.

We measured stroke volume (SV), heart rate (HR), cardiac output (Q), arterial pressure and intrapulmonic (mouth) pressure in four healthy, male subjects during simulated swimming (i.e., performing crawl movements with the legs continuously at a constant rhythm) with and without apnea (water temperature: 31 degrees C). We wanted to see whether the exercise tachycardia response persisted, or whether the HR decreased during apnea, just as in the "diving response" of diving animals. The SV and the Q fell to half its value in the control phase (i.e., swimming with normal breathing), when the 15-s apnea was performed at a high mouth-pressure; at low mouth-pressure, SV and Q hardly changed. These results are replicates of our previous findings in man during rest in air. Due to the light work, HR increased slightly from rest, but the exercise HR did not change much during apnea with or without high mouth-pressure. The results show that man tends to preserve his exercise HR response, and does not react as an oxygen-conserving animal, whether he is in air or in water under these conditions. However, man, as well as diving animals, may well have a "diving response" as an emergency reaction, which may not be restricted to only the water environment.

Adult↗
PubMed1990

Facial cold receptors and the survival reflex "diving bradycardia" in man.

We measured heart rate (HR), stroke volume (SV), systemic arterial blood pressure (BP), and mean arterial pressure (MAP) in 7 healthy volunteers in response to face immersion in water with concomitant breath-holding at different lung volumes. The subjects were at rest in the prone position. During breath-holding at total lung capacity (TLC), baseline HR (70 to 75 beats/min) fell by 10% within fractions of a second, both in the control preimmersion state when the head was surrounded by room air, and when it was immersed in water of 33 degrees C. This response was associated with rises in MAP and in SV. Immersion of the face in 10 degrees C water while breath-holding, was associated with a strong, negative chronotropic effect (22% fall in HR), which developed within 10 s. Breath-holding at functional residual capacity (FRC) reduced HR substantially only in 10 degrees C water, and in contrast to that at TLC, the response was slowly developing with a latency of 10-15 s. All these reductions in HR were significant and accompanied by increases in BP and MAP. The strong, negative chronotropic effect of cold water was typically linked to a rise in SV. The study identified two temporal components of HR reduction to face immersion: a fast parasympathetic response dependent on the input from the high pressure baroreceptors, and a late response mediated, in all likelihood, by sympathetic efferent activity. Facial receptors sensitive to cold seem to be vital in the largest responses observed. The fast response to breath-holding with the face in water of neutral temperature was equal to that in air. Thus "diving bradycardia" is in fact a basic survival response independent of water.

Adult↗