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Biomedical subjects

V Molony

Publications and source records attributed to V Molony.

At least 37 records · Page 2Linked to original sources

Feasibility of transoesophageal echocardiography for evaluation of left ventricular performance in anaesthetised horses.

Transoesophageal Doppler echocardiography was performed in 7 Thoroughbred horses anaesthetised with halothane. The procedure was performed on 4 occasions under standard conditions. On one occasion dobutamine hydrochloride was infused at 4 micrograms/kg/min for 20 min. Recordings of aortic blood velocity, obtained using high pulsed repetition frequency Doppler echocardiography (HPRF), were used to derive maximum acceleration (dv/dtmax), maximum velocity (Vmax), left ventricular ejection time (ET), pre-ejection period (PEP), velocity time integral (VTI) and cardiac output (CO). The coefficient of variation and 95% confidence intervals were narrower for the Doppler variables than for those obtained from cardiac catheterisation. For each horse the anaesthetic to anaesthetic repeatability of the Doppler indices of left ventricular function, exceeded that of maximum rate of rise of left ventricular pressure (LVdp/dtmax). The horse to horse variability was significant for heart rates Vmax, dv/dtmax, and VTI. After dobutamine infusion there were significant changes in all measured variables except heart rate, VTI and CO. The % change that occurred exceeded the predicted 95% confidence intervals for single measurements in all significantly affected variables. This suggests Doppler indices of cardiac performance may be useful to assess changes in haemodynamic function. Passage of the probe into the oesophagus was not associated with serious adverse effects. Mild serous nasal discharge was visible for up to 24 h after the horses recovered from anaesthesia. Mild nasal haemorrhage occurred on 5 occasions during probe insertion. It is concluded that transoesophageal Doppler echocardiography provides a minimally invasive, continuous method for monitoring left ventricular systolic performance in anaesthetised horses.

Adrenergic beta-Agonists↗

Effect of different methods of castration on behaviour and plasma cortisol in calves of three ages.

Calves of six, 21 and 42 days were either handled (controls) or castrated by Burdizzo, by surgical or by rubber ring techniques and their behaviour and plasma cortisol monitored for three hours after treatment. The rubber ring caused significant increases in active behaviour and abnormal postures for two hours compared with handled or castrated by Burdizzo and surgical techniques, and surgical techniques resulted in a significant increase in abnormal standing, particularly in the first 30 minutes. Abnormal behaviour and posture were recorded less frequently in six-day-old calves. The mean cortisol peaks for six-, 21- and 42-day-old calves were, respectively, 36, 31 and 23 nmol litre-1 in the handled groups; 60, 43 and 48 nmol litre-1 in the rubber ring groups; 77, 50 and 62 nmol litre-1 in the Burdizzo groups; and 106, 63 and 107 nmol litre-1 in the surgical groups. The greatest cortisol response occurred in 42-day-old surgically treated calves and the shortest response after Burdizzo castration. These responses suggest that irrespective of age, all methods of castration studied caused acute pain. Burdizzo castration appeared to produce the least pain, particularly in younger calves.

Age Factors↗

Behavioural responses of lambs of three ages in the first three hours after three methods of castration and tail docking.

The behavioural responses of groups of seven lambs were compared with control groups after castration and tail docking by rubber rings, application of a Burdizzo clamp in addition to a rubber ring and after surgical castration at five, 21 and 42 days. All methods at all ages produced changes in behaviour which were interpreted as indicative of considerable pain. The rubber ring groups showed most changes in behaviour at all ages. The rubber ring with Burdizzo groups showed least changes and some lambs in these groups showed much less response than others. The surgical groups showed some behavioural responses which were different, both qualitatively and quantitatively to those in other groups. It is concluded that indices used for recognition and assessment of acute pain received conditional support, that modification of the rubber ring with Burdizzo may provide the least painful method without local anaesthesia and that age had little effect on the responses.

Animals↗

Changes in plasma cortisol concentration in lambs of three ages after three methods of castration and tail docking.

Lambs were handled only or castrated and tail docked at five, 21 and 42 days of age by either surgery, rubber ring or rubber ring and Burdizzo. Plasma cortisol was measured in blood samples taken before and at 12, 24, 36, 48, 60, 72, 84, 96, 138 and 180 minutes after castration and docking. Pre-treatment and peak cortisol values were highest in five-day-old lambs. The peak cortisol values, at each age, were similar for surgery and rubber ring groups. However, the peak occurred earlier after surgery and rubber ring Burdizzo than after rubber ring only treatment. The cortisol peak was 28 nmol litre-1 lower after rubber ring Burdizzo than surgery or rubber ring only. Plasma cortisol returned to pretreatment values within 84 minutes after rubber ring Burdizzo, 96 to 138 minutes after rubber ring only but not within 180 minutes after surgery. The changes in plasma cortisol together with the changes in behaviour suggest that the rubber ring Burdizzo method of castration and docking of lambs at all ages, was probably the least painful of the methods tested.

Aging↗

Effects of castration on behaviour and plasma cortisol concentrations in young lambs, kids and calves.

Behavioural and cortisol responses to the husbandry practice of castration with tight rubber rings were investigated in lambs and kids one day after birth and in hand reared calves aged one to seven days. There were three treatments: control handling and blood sampling, castration and, in lambs and kids only, intravenous adrenocorticotrophin injection (ACTH). The integrated cortisol responses (area under the cortisol curve) in lambs and kids were least in control, intermediate in castrated and greatest in ACTH animals. No cortisol responses were detected in control or castrated calves. The incidences of behaviour used to assess the intensity of distress apparently experienced in the different species corresponded generally with the magnitudes of the cortisol responses. Behavioural and cortisol responses together suggested that the distress caused by castration was greatest in lambs, intermediate in kids and least but not necessarily absent in hand reared calves.

Adrenocorticotropic Hormone↗

Effects of local anesthesia and intravenous naloxone on the changes in behaviour and plasma concentrations of cortisol produced by castration and tail docking with tight rubber rings in young lambs.

The reliability of some behavioral and physiological indices used for the recognition and assessment of acute pain in lambs after castration and tail docking has been examined. Changes in the indices were measured after blocking neural activity with local anaesthetic (lignocaine) and after an opioid antagonist (naloxone) was administered. Six lambs, aged less than one week, were allocated randomly to each of six treatments. (i) control handling and blood sampling; (ii) castration plus tail docking with tight rubber rings; (iii) local anaesthesia; (iv) local anaesthesia followed by castration and tail docking; (v) intravenous naloxone only (0.2 mg kg-1); and (vi) intravenous naloxone followed by castration and tail docking. Local anaesthesia eliminated the behavioural and plasma cortisol changes which usually follow castration and tail docking. Naloxone had a limited effect on the increase in cortisol but altered the behaviour. The results support the view that such indices are useful for assessment of the response to acute pain and that, although endogenous opioids do reduce pain in young lambs after castration and tail docking, the effect is small.

Anesthesia, Local↗

The involvement of neurokinin receptor subtypes in somatosensory processing in the superficial dorsal horn of the cat.

As well as substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) have recently been found in the superficial dorsal horn of the spinal cord; NKA originating mainly in fine primary afferents. We have investigated the effects of these tachykinins and a range of analogues on somatosensory responses of single identified dorsal horn neurons, when applied ionophoretically to the region of the substantia gelatinosa. Behavioural reflex tests of thermal nociception were carried out in parallel. The role of NK-1, NK-2 and NK-3 receptors was addressed. NK-1-selective agonists attenuated the non-nociceptive responses of identified multireceptive spinocervical tract (SCT) neurons. Of the endogenous tachykinins, both SP and NKB (a weak NK-1 agonist) showed this effect. No role for NK-3 receptors was identified in our experiments. NK-2-selective agonists (including NKA) caused a unique and selective facilitation of thermal nociceptive responses. NKA also reduced reflex response latency in tail-flick and hot plate tests. NKA as a primary afferent transmitter may thus be involved in mediating or facilitating the expression of thermal nociceptive inputs in the substantia gelatinosa. NKA and SP could be considered as acting in concert in the superficial dorsal horn in an effectively pro-nociceptive modulatory role. Evidence from receptor-selective antagonists supports that obtained with agonists for the roles of particular NK receptors in somatosensory processing. NK-2, but not NK-1 or NK-3 antagonists attenuated endogenous thermal nociceptive responses, supporting the hypothesis that an NK-2 agonist (such as NKA) may normally participate in expression of thermal nociception in the superficial dorsal horn. Behavioural experiments showing increased response latencies with a putative NK-2 selective antagonist further supported the involvement of NK-2 receptors in thermal nociception.

Animals↗

The influence of opioid receptor subtypes on the processing of nociceptive inputs in the spinal dorsal horn of the cat.

Extracellular recordings were made of the cutaneous sensory responses of spinocervical tract (SCT) neurones in the lumbar dorsal horn of anaesthetised and paralysed cats. All of the neurones studied were multireceptive, showing excitatory responses to both innocuous and noxious (thermal and when tested, mechanical) stimuli applied to their cutaneous receptive fields on the ipsilateral hindlimb. The effects of iontophoretically applied opioids were studied on a regular cycle of responses to these cutaneous stimuli and also to D.L-homocysteic acid (DLH). In the first series of experiments, drugs were applied in the vicinity of the SCT neurones. The kappa-receptor agonists dynorphin A(1-13) and U50488H, but not dynorphin A(2-13), the mu-agonist DAGO, or the delta-agonist DADL, caused a selective reduction of the nociceptive responses of the neurones. The corresponding responses to innocuous stimuli or to DLH, and spontaneous activity were unaffected. In the second series of experiments, drugs were applied from a second electrode placed in the region of the substantia gelatinosa directly dorsal to the tip of the recording electrode. Under these conditions, the mu-receptor agonist DAGO, but not the kappa-agonist dynorphin A(1-13) or the delta-agonists DADL, DSLET or DLPEN, showed a selective antinociceptive effect. In both series, the antinociceptive effects of the opioids were readily reversed by iontophoretically applied naloxone. The effect of dynorphin A(1-13) applied close to SCT neurones, but not that of DAGO applied in the region of the substantia gelatinosa, was reversed by the alpha 2-adrenoceptor antagonist, idazoxan. The results indicate that both mu- and kappa-opioid receptors (at anatomically distinct sites) can participate in the selective antinociceptive influence that opioids can exert over somatosensory information ascending to supraspinal levels. The antagonism of kappa-receptor-mediated antinociception by idazoxan is consistent with an interaction of opioid and noradrenaline influences at the level of the dorsal horn.

Animals↗

Membrane properties of nociceptive neurones in lamina II of lumbar spinal cord in the cat.

1. Intracellular recordings were made from neurones in lamina II of the dorsal horn of the lumbar spinal cord of the cat, and the electrotonic responses to brief rectangular current pulses of up to 0.5 nA passed through the recording microelectrode measured. 2. The majority of penetrations were associated with input resistances lower than 70 M omega, low resting potentials (-25 to -45 mV) and frequent firing of action potentials. Stable resting potentials of -50 to -75 mV were recorded in twenty neurones which exhibited continuous ongoing synaptic activity without action potentials. The threshold for action potential initiation was around -42 mV. The current-voltage relationships were linear over most of the range of currents used; with depolarizing currents rectification became apparent close to the firing threshold. Input resistances ranged from 80 to 150 M omega. 3. The time course of the decay of the electrotonic response was exponential with a time constant of 0.8-2.0 ms. The morphology of the cells--small soma with a small number of fine processes--and these short time constants suggest that axial current flow is limited and that the charge is dissipated locally within the soma through the membrane capacitance. 4. Effective membrane capacities were calculated from the estimated soma surface area of typical neurones in lamina II stained with HRP, and assuming a specific membrane conductance of 1.0 microF cm-2 they ranged from 3.1 to 15.7 pF. Membrane capacities were calculated for the twenty neurones in this study from measurement of input resistance and time constants (6.4-15.0 pF) and lay within this range. 5. Three neurones which had their electrical properties measured were also stained with horseradish peroxidase (HRP). Their specific membrane capacitances (1.1-1.2 microF cm-2) and specific resistances (0.9-1.1 k omega cm2) were within the range of values measured for other neurones in the CNS. 6. The short time constants found for these neurones suggests that temporal summation of postsynaptic potentials evoked by short-acting neurotransmitters will be limited. This may help to explain why action potentials arise singly from discrete, short-lived EPSPs. There is anatomical evidence for multiple connections from terminal branches of A delta and C afferent fibres within the superficial dorsal horn; this suggests that spatial summation of EPSPs is a major factor in synaptic integration of some of the primary afferent inputs to these neurones.

Action Potentials↗

Respiratory responses of the domestic fowl to low level carbon dioxide exposure.

Respiratory function in the restrained, conscious domestic fowl was measured using a non-invasive technique and computer aided analysis to examine respiratory flow, and in-dwelling arterial catheters to monitor blood carbon dioxide levels. The effects of two low ranges of inspiratory carbon dioxide (0.2 to 1.0 per cent and 0.25 to 2.25 per cent) were studied, simulating levels of carbon dioxide that may occur in commercial poultry units and representing a mild environmental stress for the birds. A linear increase in minute volume with inspiratory carbon dioxide was observed, due primarily to increases in tidal volume. Arterial carbon dioxide (PaCO2) tension also rose as the inspiratory carbon dioxide concentration was raised, but higher inspiratory carbon dioxide levels were required to affect significantly blood carbon dioxide concentration than to modify respiratory parameters. Variation was observed in the individual bird's response to carbon dioxide (bird X carbon dioxide interaction), suggesting that resting values of the respiratory parameters measured were important in determining the bird's ventilatory response to carbon dioxide.

Analysis of Variance↗

Variability in respiratory function of the domestic fowl.

Several respiratory parameters were measured in five groups of hens to estimate the variation in respiratory function of the general hen population. A non-invasive technique was used to measure respiratory flow, with computer-aided analysis of the data, and the results were examined statistically. Using different groups of hens, additional information was obtained regarding possible sources of variation between individual hens, such as egg laying condition, age and health. Significant differences between individuals within the groups were observed, but there were also changes in breath-to-breath variation for individual hens. While some changes in the variation between birds were observed from one group to another, variation within individual birds made interpretation of the results difficult. Repeated measurements made on one group revealed significant changes in minute volume with time, but the changes were not related to learning. Significant interactions between hens and time of measurement occurred for certain parameters, showing that the individuals' responses changed with time in different ways. The groups of hens were compared to observe whether they represented the same or distinct populations, and were found to overlap to varying extents for different respiratory parameters. Single respiratory variables and weighted combinations of certain variables were also used to separate the groupings, as a possible diagnostic method for partitioning groups of hens.

Animals↗

An alpha 2 receptor mediates the selective inhibition by noradrenaline of nociceptive responses of identified dorsal horn neurones.

Extracellular recordings were made of 59 neurones with long, ascending projections (spinocervical tract (SCT) and dorsal column postsynaptic (DCPS) neurones) in the lumbar dorsal horn of anaesthetized and paralyzed cats. All showed prominent excitatory responses to innocuous stimuli, applied to their cutaneous receptive fields on the ipsilateral hindlimb. The majority of the population investigated (83%) was multireceptive, being activated by noxious as well as innocuous cutaneous stimuli. Drug effects were examined on a regular cycle of responses to these cutaneous stimuli and also to DL-homocysteic acid (DLH). In 49 multireceptive SCT and DCPS neurones, ionophoretically-applied L-noradrenaline (NA) produced a potent selective inhibition of the nociceptive responses (to heat or pinch) in 40 out of 44 SCT and 3 out of 5 DCPS neurones, with no statistically significant change in the responses to innocuous brush or DLH, or in spontaneous activity. NA had no effect on the majority of cells (8 out of 11) that responded only to innocuous stimuli. In 19 SCT neurones that showed NA-selectivity, the alpha 2-selective agonists clonidine (in 12 out of 15) and metaraminol (in 2 out of 3) mimicked this selective effect, whereas, the alpha 1 agonist, phenylephrine and the beta agonist, isoprenaline did not. Furthermore, the alpha 2 antagonists, yohimbine and idazoxan (RX781094), either reversed or reduced the potency of the NA-elicited inhibition of nociceptive responses in all 7 SCT neurones tested. These results are discussed in relation to other evidence for spinal antinociceptive effects of noradrenergic systems acting at a spinal level and the possible involvement of an alpha 2 receptor in such effects.

Animals↗

Nociceptive neurones in the superficial dorsal horn of cat lumbar spinal cord and their primary afferent inputs.

The morphology, background activity and responses to stimulation of primary afferent inputs of small neurones in the superficial dorsal horn which could only be excited from the skin by noxious stimulation were investigated by intracellular recording and ionophoresis of HRP. Neurons which gave similar responses to afferent stimulation were morphologically heterogeneous with respect to dendritic tree geometry and axonal projection, but were located around the lamina I/II border. Cutaneous excitatory receptive fields responding to noxious stimulation were generally small; most neurones had more extensive inhibitory fields responding to innocuous mechanical stimulation, in many cases overlapping the excitatory fields. Generally, stimulation of the excitatory field resulted in depolarization of the neurone and increased action potential firing, and stimulation of the inhibitory field resulted in hyperpolarization. Electrical stimulation of peripheral nerves revealed the existence of converging excitatory inputs carried by different fibre groups, and all neurones received an inhibitory input activated at low threshold. Excitatory responses were short-lived and occurred consistently in response to repeated stimulation. Central delay measurements gave evidence of a number of A delta monosynaptic inputs but only one A beta monosynaptic input; inhibitory inputs along A beta fibres were polysynaptic. The constant latency and regularity of the C response suggested monosynaptic connections. Low intensity stimulation of inhibitory inputs elicited a short-lived i.p.s.p. which increased in amplitude with increasing stimulus strength until it disappeared into a more prolonged hyperpolarization. This was associated with inhibition of background action potentials, and increased in duration with increasing stimulus strength up to C levels, indicating an A delta and C component. It is suggested that the level of excitability of these neurones depends on the relative amounts of concurrent noxious and innocuous stimulation, and that the resultant output, which is conveyed mainly to other neurones within the spinal cord, could modulate reflex action at the spinal level as well as affecting components of ascending sensory pathways.

Action Potentials↗

Ventilatory and cardiovascular responses of the unanaesthetized chicken, Gallus domesticus, to the respiratory stimulants etamiphylline and almitrine.

The ventilatory and cardiovascular effects of i.v. administration of the respiratory stimulants etamiphylline and almitrine were investigated in conscious or decerebrate adult female domestic fowl. Infusion of etamiphylline (100 mg . kg-1) or injection of almitrine (2 mg . kg-1) evoked a potent long-lasting stimulation of ventilation in both conscious and decerebrate fowl. The pattern of the respiratory response was characteristically different to that observed in mammals in that the increased minute volume of ventilation was attained by large increases in respiratory frequency accompanied by a reduction in tidal volume. The pattern of respiration following drug-induced stimulation was, in some birds, typical of thermal panting although neither etamiphylline nor almitrine caused significant increases in body temperature. Differences in the pattern of responses of the rate and depth of breathing may be attributed in part to the differences in pulmonary receptor systems involved in the control of breathing in birds and mammals.

Almitrine↗

Statistical analysis of ongoing activity of neurones in the substantia gelatinosa and in lamina III of cat spinal cord.

Intracellular recordings from substantia gelatinosa (s.g.) neurones in chloralose-anaesthetized cats and in decerebrate preparations revealed the existence of ongoing synaptic activity. 59% of s.g. neurones showed ongoing spiking activity at rates of more than one per second. The ongoing activity of twenty s.g. neurones was subjected to statistical analysis. Stationarity was established for the activity of each neurone, the interspike interval (i.s.i.) distributions were bell-shaped, and no evidence of dependency of the length of an interval on the one preceding it was found. The mechanism of spike generation in these neurones is therefore an example of a renewal stochastic process. The pattern of ongoing discharge of twelve neurones recorded in lamina III was markedly different, and generated in each case a unimodal asymmetric i.s.i. histogram with a sharp rise to mode after a short dead time and a slow decay. The activity was stationary only in the long term, and there was strong evidence of dependency of intervals. The spike generating mechanism was therefore an example of a non-renewal stochastic process. The different patterns of activity are discussed in relation to differences in cutaneous input, and it is suggested that the pattern of activity in the s.g. neurones is the result of convergence on the neurones of a large number of small independent excitatory influences, whereas that of the neurones in lamina III is the result of excitation by powerful synchronous synaptic inputs. It is re-emphasized that statistical analysis of neural impulse sequences is a valuable technique in investigation of the function of a neurone within its network.

Anesthesia, General↗

Intracellular marking of identified neurones in the superficial dorsal horn of the cat spinal cord.

Intracellular iontophoresis of horseradish peroxidase has been used to mark identified neurones in the superficial dorsal horn of cats. The cats were anaesthetized with alpha-chloralose and paralysed with gallamine triethodide. Four specific nocireceptive neurones in the marginal zone and seven neurones in the substantia gelatinosa were recovered. One of the former and four of the latter are described in detail and are illustrated as reconstructions from serial sections. The results confirm previous conclusions that the substantia gelatinosa contains neurones classified as 'inverse' and that the nocireceptive neurones of lamina I are Waldeyer Cells.

Animals↗