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Biomedical subjects

A L Clark

Publications and source records attributed to A L Clark.

At least 127 records · Page 7Linked to original sources
PubMed1993

Relationship between ventilation and carbon dioxide production in normal subjects with induced changes in anatomical dead space.

The aim of this study was to test the hypothesis that the increased ventilation to carbon dioxide production relationship on exercise associated with chronic cardiac failure may be due in part to changes in respiratory pattern, causing an increase in anatomical dead space ventilation. In order to assess the effect of changes in respiratory pattern on the relationship between ventilation and carbon dioxide production, normal subjects exercised at the same level at three different respiratory rates (normal, 25% slower, 25% faster). Nine healthy subjects were recruited from amongst hospital staff volunteers. Minute ventilation, carbon dioxide production and oxygen consumption were measured. There were no significant changes in ventilation, carbon dioxide production, or the correlation between ventilation and carbon dioxide production. This finding lends support to the view that changes in respiratory pattern can only be responsible for a very small proportion of the VE/VCO2 slope difference between chronic cardiac failure and normals.

Adult↗
PubMed1992

Relation between ventilation and carbon dioxide production in patients with chronic heart failure.

OBJECTIVES: The aim of this study was to analyze the relation between ventilation and carbon dioxide production and the control of ventilation in patients with chronic heart failure. BACKGROUND: Patients with chronic heart failure exhibit an increased ventilatory response to exercise. Ventilation is closely linked to carbon dioxide production, producing a high correlation between the two variables. This relation is nonlinear at high levels of exercise. METHODS: The ventilation/carbon dioxide production ratio during exercise was examined in 29 patients with chronic heart failure and 9 normal volunteers. RESULTS: In the patients with heart failure, there were three patterns: in the least severely affected patients, the pattern was similar to that of the normal subjects, with an initial decrease in the ventilation/carbon dioxide production ratio to a plateau maintained during exercise; in more severely affected patients, there was an increase in the ratio at the end of exercise, and in the most severely affected patients, the ratio increased from the outset of exercise. The ventilation/carbon dioxide relation is not adequately described by a straight line relation. CONCLUSIONS: The ventilation/carbon dioxide ratio is not fixed, and the changes that occur in this ratio reflect either a noncarbon dioxide-driven ventilatory stimulus or an increase in ventilation-perfusion mismatch due to increased dead space ventilation. The different patterns of this ratio may provide clues to the pathophysiologic mechanisms of the excessive ventilation and breathlessness seen during exercise in chronic heart failure.

Adult↗
PubMed1987

Cauda equina and lumbar nerve root compression in patients with AIDS.

Five patients known to be HIV (human immunodeficiency virus)-positive--that is, susceptible to AIDS--presented with symptoms initially thought to be indicative of lumbar disc lesions. Signs of nerve root or cauda equina compression were found in all five patients. Lumbar radiculography and, in one patient, computerised tomography produced no evidence of compressive pathology. We recommend that orthopaedic surgeons exercise caution in diagnosing nerve root compression in patients who may be HIV-positive.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Characteristics of phasic and tonic sympathetic ganglion cells of the guinea-pig.

Intracellular recording techniques have been used to determine the electrophysiological properties of sympathetic neurones in ganglia of the caudal lumbar sympathetic chain (l.s.c.) and in the distal lobes of inferior mesenteric ganglia (i.m.g.) isolated from guinea-pigs. Passage of suprathreshold depolarizing current initiated transient bursts of action potentials in 97% of l.s.c. neurones, but only 13% of i.m.g. cells ('phasic' neurones). Most i.m.g. neurones fired continuously during prolonged depolarizing pulses ('tonic' neurones). Passive membrane properties varied; mean cell input resistance was similar between groups, but phasic neurones had smaller major input time constants on average than had tonic cells. Current-voltage relations determined under both current clamp and voltage clamp were linear around resting membrane potential (approximately 60 mV), where membrane conductance was lowest. Instantaneous and time-dependent rectification varied in the different neurone types. The current underlying the after-hyperpolarization following the action potential was significantly larger on average in tonic i.m.g. cells than in phasic neurones, although its time course (tau = 100 ms) was similar. Phasic neurones fired tonically when depolarized after adding the muscarinic agonist, bethanechol (10(-5) M to 10(-4) M), to the bathing solution. Bethanechol blocked a proportion of the maintained outward current (presumably the M-current, IM, Adams, Brown & Constanti, 1982) in phasic neurones; this current was small or absent in tonic neurones. Transient outward currents resembling the A-current (IA, Connor & Stevens, 1971 a) were evoked in tonic but not in phasic neurones by depolarization from resting membrane potential. IA could only be demonstrated in phasic neurones after a period of conditioning hyperpolarization. After a step depolarization to approximately --50 mV, IA reached peak amplitude at about 7 ms and then decayed with a time constant of about 25 ms in both neurone types. Activation characteristics of IA were similar for phasic and tonic neurones, but inactivation curves, although having the same shape, were shifted to more depolarized voltages in tonic neurones. That is, IA was largely inactivated at resting membrane potential in phasic, but not tonic neurones. It is concluded that the discharge patterns of the two populations of sympathetic neurones result from differences in the voltage-dependent potassium channels present in their membranes. The anatomical occurrence of the different cell types suggests that phasic neurones are vasoconstrictor and tonic neurones are involved with visceral motility.

4-Aminopyridine↗
PubMed1984

Nature of the anticholinesterase-induced repetitive response of rat and mouse striated muscle to single nerve stimuli.

The action of the anticholinesterase Paraoxon on neuromuscular transmission in rat diaphragm and mouse omohyoideus preparations was investigated. In both preparations, when Paraoxon potentiated the twitch in response to a single nerve stimulus, repetitive muscle action potentials were recorded with an intracellular electrode placed at the motor end-plate region. At end-plates of Paraoxon-treated rat diaphragm preparations where the membrane potential was not sufficiently negative to support muscle action potentials, repetitive end-plate potentials were recorded in response to a single nerve stimulus. No repetitive end-plate potentials could be recorded under such conditions in preparations which had been exposed to dithiothreitol before being treated with Paraoxon, although twitch potentiation and repetitive muscle action potentials were still observed in these preparations. In Paraoxon-treated mouse omohyoideus preparations only single end-plate potentials were recorded from end-plates where the membrane potential was not sufficiently negative to support muscle action potentials. This applied whether or not the preparation had been treated with dithiothreitol before being exposed to Paraoxon. In voltage-clamped rat diaphragm preparations which had been treated with Paraoxon, repetitive end-plate currents were frequently recorded in response to a single nerve stimulus. Under the same conditions mouse omohyoideus preparations responded with a single end-plate current. It is concluded that Paraoxon-induced twitch potentiation in rat diaphragm and mouse omohyoideus preparations is caused by repetitive muscle action potentials being triggered by a single nerve stimulus. Under the conditions stated, the repetitive muscle action potentials in rat diaphragm preparations arose from a prolonged end-plate potential or repetitive end-plate potentials or a combination of both. In mouse omohyoideus preparations the repetitive muscle potentials were the consequence of a single prolonged end-plate potential.

Action Potentials↗
PubMed1983

Twitch potentiation by organophosphate anticholinesterases in rat phrenic nerve diaphragm preparations.

1 Twitch potentiation produced by anticholinesterases has been variously attributed to the prolonged postjunctional action of acetylcholine (ACh), a prejunctional action of ACh involving the initiation of antidromic firing (ADF) in the nerve or a direct action of the anticholinesterases on nerve terminals initiating ADF. 2 The organophosphate anticholinesterases, paraoxon (diethyl-4-nitrophenylphosphate) and DFP (diisopropyl fluorophosphate), when applied to rat isolated diaphragm preparations for 30 min, produced twitch potentiation which subsequently declined. 3 The rates of onset and decline of twitch potentiation were directly related to the concentration of the organophosphates and the reversibility of their effects was in line with the reactivation of the phosphorylated enzymes formed by them, whether reactivation was spontaneous or induced by the oxime, N,N'-trimethylene-1, 3-bis(pyridinium-4-aldoxime). 4 Reducing the output of ACh from nerve terminals (by reducing the ratio of calcium: magnesium ions in the bathing solution) or reducing the affinity of ACh for the nicotinic cholinoceptor (using the disulphide bond reducing agent, dithiothreitol) produced the same effects as did lowering the concentration of the organophosphates. 5 It is concluded that the twitch potentiation produced by paraoxon and DFP, and its failure to be maintained when the higher concentrations of the organophosphates were used, were the direct result of the excess of ACh in the synaptic cleft, following inhibition of acetylcholinesterase.

Acetylcholine↗
PubMed1983

Effects of pancuronium and hexamethonium on paraoxon-induced twitch potentiation and antidromic firing in rat phrenic nerve diaphragm preparations.

The actions of pancuronium, a selective antagonist of acetylcholine (ACh) at nicotinic cholinoceptors at motor endplates, and hexamethonium, a selective antagonist of ACh at nicotinic cholinoceptors in autonomic ganglia, have been studied in rat phrenic nerve diaphragm preparations. The effects on paraoxon-induced twitch potentiation and antidromic firing (ADF) in the phrenic nerve, were compared with the effects on normal twitch tension and intracellularly recorded miniature endplate potentials (m.e.p.ps) and endplate potentials (e.p.ps.) In preparations exposed to paraoxon, pancuronium was found to be approximately 10 times more effective in reducing the potentiated component of the twitch than the component which corresponded to the pre-paraoxon twitch. A similar result was obtained with hexamethonium. Pancuronium and hexamethonium, in concentrations which reduced paraoxon-induced twitch potentiation but had no effect on the twitch tension of preparations not treated with paraoxon, reduced paraoxon-induced ADF. The lowest concentrations of pancuronium and hexamethonium required for this also reduced the amplitude of m.e.p.ps and e.p.ps. Dithiothreitol, a disulphide bond reducing agent which reduces the affinity of ACh for nicotinic cholinoceptors, enhanced the potency of pancuronium 2 to 3 fold. The same also applied for hexamethonium. It is concluded that the experiments failed to provide evidence for an action of ACh on prejunctional nicotinic cholinoceptors of the ganglionic-type being involved in the initiation by paraoxon of twitch potentiation and ADF. Furthermore, the results obtained can be explained by pancuronium and hexamethonium reducing the action of ACh at the postjunctional membrane.

Animals↗
PubMed1983

The relationship between stimulus-induced antidromic firing and twitch potentiation produced by paraoxon in rat phrenic nerve-diaphragm preparations.

The relationship between stimulus-induced repetitive antidromic firing (ADF) in the motor nerve and twitch potentiation produced by the organophosphate anticholinesterase paraoxon, has been investigated in rat diaphragm preparations. Little or no ADF was produced by paraoxon in preparations bathed in a Tyrode solution containing 1 mM calcium and 1 mM magnesium ions although the preparations showed marked twitch potentiation. Increases in the calcium:magnesium ion ratio produced a ratio-dependent increase in the ADF but had no consistent effect on peak twitch potentiation. Dithiothreitol, a disulphide bond reducing agent which decreases the affinity of acetylcholine for nicotinic cholinoceptors, abolished ADF but only modified the time course of twitch potentiation. Dithiothreitol, a disulphide bond reducing agent which decreases the affinity of acetylcholine for nicotinic cholinoceptors, abolished ADF but only modified the time course of twitch potentiation. It is concluded that the initiation of ADF is a consequence of the prolonged action of acetylcholine within the synaptic cleft following inhibition of acetylcholinesterase, and that ADF is not the only mechanism by which twitch potentiation can be produced.

Animals↗
PubMed1983

Effect of dithiothreitol on agonist and antagonist actions in frog muscle.

The effects of the disulphide bond reducing agent dithiothreitol (DTT) in the frog rectus abdominis preparation have been investigated. DTT, 1 mM, reduced the potency of the monoquaternary agonists acetylcholine, carbachol and tetramethylammonium and the response to electrical field stimulation; the same applied to nicotine, but the action of edrophonium was unaffected and that of the bisquaternary agonist, decamethonium, was increased. The potency of tubocurarine and gallamine as antagonists was unaltered or slightly reduced by DTT when monoquaternary agonists were used and increased when decamethonium was used as agonist. All these effects of DTT were reversed by the oxidizing agent 5-5'dithiobis(2-nitrobenzoic acid) and can be explained by a reduction of a disulphide bond in the vicinity of the anionic site of the nicotinic cholinoceptor. Comparison between these results and published data indicate that there are species differences between nicotinic cholinoceptors and motor endplates. In the guinea-pig ileum preparation DTT reduced the potency of nicotine acting at ganglionic nicotinic cholinoceptors, but had no effect on the agonist response mediated via muscarinic cholinoceptors.

Acetylcholinesterase↗
PubMed1976

The inhibitory effect of gallamine on muscarinic receptors.

1 The inhibitory effect of gallamine (1.1 muM-1.1 mM) on negative inotropic responses to acetylcholine (ACh) or carbachol (CCh) was investigated in isolated electrically stimulated atria of the guinea-pig. Gallamine caused parallel rightward shifts of the dose-response curves to the agonists, with no depression of the maximal response. 2 Gallamine (0.11 - 1.1 mM) produced a greater degree of antagnism towards CCh than towards ACh. With either agonist, the degree of antagonism produced by gallamine in high concentrations was less than that expected for a competitive antagonist.. 3 Similar findings were made when either negative inotropic or chronotropic responses were recorded in spontaneously beating guinea-pig atria. The inhibitory effect of gallamine against the negative inotropic response to cholinomimetics in electrically stimulated atria was not altered either in the presence of propranol (17 muM) or in atria obtained from guinea-pigs pretreated with diisopropylphosphorofluoridate (DEP) 12.5 mumol/kg, in divided doses over 3 days). 4 When ACh was used as the agonist, combination of gallamine with atropine (0.05-0.4 muM) produced dose-ratios which were less than expected for combination of two competitive antagonists. The same phenomenon was observed in atria obtained from guinea-pigs pretreated with DFP. 5 It is suggested that the antagonism produced by gallamine is a type of non-competitive inhibition, which has been termed "metaffinoid antagonism". An antagonist of this type allosterically alters the affinity of the agonist for its binding site, rather than changing the effectiveness of the agonist-receptor interaction.

Acetylcholine↗