Biomedical subjects

W K Milsom

Publications and source records attributed to W K Milsom.

At least 37 records · Page 2Linked to original sources

PubMed1999

Lung deflation stimulates fictive ventilation in decerebrated and unidirectionally ventilated toads.

We describe how the degree of lung inflation and hypercapnia influenced fictive ventilation in five toads (Bufo marinus) that were decerebrated and paralysed with roccuronium. Both lungs were unidirectionally ventilated and the degree of lung inflation was determined by controlling the outflow resistance of these catheters, while ventilatory motor output was assessed on the basis of nervous activity in the mandibular branch of the Vth cranial nerve. The pattern of the recorded activity ('fictive ventilation') resembled the ventilatory patterns previously described for conscious toads. Increasing the fraction of CO2 in the gas mixture used for unidirectional ventilation from 0.00 to 0.05 stimulated fictive breathing. Fictive ventilation was also greatly stimulated, at all CO2 levels, by reduced lung volume, while complete inflation of the lungs abated fictive ventilation at all levels of CO2. Stimulation of CO2 sensitive chemoreceptors and pulmonary stretch receptors appear to have interactive effects on the central generation of ventilatory output in toads.

Animals↗

PubMed1999

Cardiovascular and respiratory reflexes: the tropical fish, traira (Hoplias malabaricus) O2 chemoresponses.

To determine the location and distribution of chemoreceptors involved in the cardiovascular and respiratory responses to hypoxia of traira (Hoplias malabaricus), we measured heart rate, arterial blood pressure, ventilation frequency and amplitude of opercular movements during exposure to hypoxia and application of NaCN to either water bathing the gills (external) or the ventral aortic blood (internal). This was done before and after selective denervation of branchial branches of the IXth and Xth cranial nerves to various gill arches. The data suggest that hypoxia elicits a bradycardia that arises from internal receptors located in the first gill arch. They also indicate the presence of branchial and extra branchial O2-chemoreceptors that reflexively elevate systemic vascular resistance during hypoxia. Hypoxia induced increases in ventilation frequency arose primarily from external receptors located exclusively within the gills while increases in breathing amplitude also involved extra branchial receptors. In addition, the data suggest there are O2 sensitive chemoreceptors located in the first gill arch that attenuate the respiratory responses.

Animals↗

PubMed1999

The effect of isovolemic anaemia on blood O2 affinity and red cell triphosphate concentrations in the painted turtle (Chrysemys picta).

The blood oxygen affinity of vertebrates is regulated, in part, through changes in red cell phosphate levels and increased oxygen affinity during reductions in inspired oxygen and is a well-described and common feature. However, during anaemia, when oxygen delivery is compromised by a reduction in blood oxygen carrying capacity, a lowering of blood oxygen affinity will facilitate oxygen unloading in the tissues, while oxygen loading at the gas exchange organ is not impaired. The present study investigated the effects of artificially induced anaemia in vivo on the blood oxygen affinity and red cell nucleoside triphosphate (NTP) concentrations in the turtle, Chrysemys picta. Blood was obtained from conscious animals through an arterial catheter and oxygen equilibrium curves were determined using the Tucker method while NTP concentrations were analyzed spectrophotometrically. Before induction of anaemia haematocrit averaged 23% and P50 was 18.5 +/- 0.7 with a NTP/Hb of 0.20 +/- 0.01 (mmol/mmol). After the haematocrit had been reduced to approximately 10% by bleeding (48-96 h) (blood volume was maintained by re-infusion of plasma and Ringer) there were no effects on P50 or red cell NTP concentrations. Thus, in contrast to fish and mammals, turtles do not exhibit a change in blood oxygen affinity during anaemia.

Anemia↗

PubMed1999

Central respiratory pattern generation in the bullfrog, Rana catesbeiana.

There are two components to breathing pattern generation the production of the pattern of neural discharge associated with individual breaths, and the pattern in which breaths are produced to effect ventilation. Bullfrogs typically breathe with randomly distributed breaths. When respiratory drive is elevated, breathing becomes more regular and often episodic. Studies on in vitro brainstem-spinal cord preparations of the adult bullfrog and in situ preparations of decerebrate, paralyzed, unidirectionally ventilated animals suggest that output from the central rhythm generator in frogs is conditional on receiving some input and that a host of central inputs remain even in the most reduced preparations. There appear to be descending inputs from sites in the dorsal brainstem just caudal to the optic chiasma that cluster breaths into episodes, a strong excitatory input caudal to this site but rostral to the origin of the Vth cranial nerve and, possibly, segmental rhythm generators throughout the medulla that are normally entrained to produce the normal breathing pattern. The data also suggest that the shape of the discharge pattern (augmenting, decrementing) and timing of outputs (alternating vs synchronous) associated with motor outflow during each breath are also dependent on the interconnections between these various sites.

Animals↗

PubMed1999

Regulation of cardiac rhythm in hibernating mammals.

The dramatic fall in heart rate exhibited by mammals entering hibernation begins before there is any noticeable fall in body temperature. The initial, progressive decrease in heart rate is the result of a cyclic parasympathetic activation that induces skipped beats and regular asystoles as well as slows the even heart beat. As body temperature subsequently falls, the parasympathetic influence is progressively withdrawn and periods of parasympathetic and sympathetic dominance alternate and give rise to regular periods of arrhythmia (tachycardia followed by bradycardia), and occasional long asystoles or periods of highly irregular cardiac activity. Superimposed on this is a vagally-mediated, respiratory sinus arrhythmia that is accentuated in species that breathe episodically. These events give way to a uniform heart rate in deep hibernation at low temperatures where both parasympathetic and sympathetic tone appear absent. The complete absence of tone is not a function of reduced temperature but is reflective of the state of deep, steady state hibernation. The elevation in heart rate that accompanies the onset of arousal is the result of dramatic increases in sympathetic activation that precede any increases in body temperature. As body temperature then rises, sympathetic influence is slowly withdrawn. Arrhythmias are also common during natural arousals or shifts from lower to warmer hibernation temperatures as periods of parasympathetic and sympathetic dominance again alternate en route to re-establishing a steady state in euthermia. The mechanism behind, and the biological significance of, cardiac changes mediated through orchestrated arrhythmias remain unknown.

Animals↗

PubMed1999

Cardiorespiratory responses of the toad (Bufo marinus) to hypoxia at two different temperatures.

Central vascular blood flows and ventilation were measured in conscious toads (Bufo marinus) at 15 and 25 degrees C. The animals were exposed to hypoxia (Fi(O)(sum)=0.10 and 0.05, where Fi(O)(sum) is the fractional oxygen concentration of inspired air) at both temperatures. In addition, the cardiorespiratory responses to hypercapnia (Fi(CO)(sum)=0.05) and atropine injection (5 mg kg(-)(1); 7.4 micromol kg(-)(1)) were studied at 25 degrees C. At 25 degrees C, systemic blood flow ( q_dot (sys)) exceeded pulmocutaneous blood flow ( q_dot (pc)), indicating a large net right-to-left shunt ( q_dot (pc)/ q_dot (sys) was 0.39). q_dot (pc)/ q_dot (sys) was reduced significantly to 0.22 at 15 degrees C. At both temperatures, q_dot (pc) increased significantly during hypoxia (from 26.2 to 50.8 ml min(-)(1 )kg(-)(1) at 25 degrees C and from 11. 2 to 18.9 ml min(-)(1 )kg(-)(1) at 15 degrees C), whereas q_dot (sys) changed little (from 77.2 to 66.2 ml min(-)(1 )kg(-)(1) at 25 degrees C and from 54.3 to 50.1 ml min(-)(1 )kg(-)(1) at 15 degrees C). As a result, the net right-to-left shunt was greatly reduced, while total cardiac output remained almost unaffected. The ventilatory response was more pronounced during hypercapnia but, since q_dot (pc) and q_dot (sys) were affected similarly, there was no change in the shunt pattern. In undisturbed toads at 25 degrees C, atropine injection increased q_dot (pc) and eliminated the net right-to-left shunt. This is consistent with the known vagal innervation of the pulmonary artery. The present study shows that the cardiac right-to-left shunt that prevails in undisturbed and resting toads is reduced with increased temperature and during hypoxia. These findings are consistent with the general view that the cardiac right-to-left shunt is regulated and reduced whenever oxygen delivery is compromised or metabolic rate is increased.

Animals↗

PubMed1998

Cortical activation states in sleep and anesthesia. I: Cardio-respiratory effects.

Under light urethane anesthesia, animals cycle through patterns of EEG activity which superficially appear like waking, light sleep and slow-wave sleep patterns (States I, II and III, respectively) in unanesthetized animals. The present study questioned whether similar cortical activity patterns in anesthetized and unanesthetized golden mantled ground squirrels represented analogous states in terms of cardiorespiratory function. Sleep exerted a strong negative influence on breathing frequency and ventilation, but had less consistent effects on tidal volume. Urethane-anesthetized animals demonstrated exactly the same alterations in respiratory variables when switching between states with similar cortical activity. Cardiovascular function was also affected by arousal state; heart rate decreased and variation increased significantly as animals moved from wake into sleep. Although urethane anesthesia greatly increased heart rate and abolished respiratory sinus arrhythmia, state-dependent changes in heart rate were still evident. Overall, the states observed under urethane anesthesia mimicked sleep/wake in terms of their effect on cardio-respiratory function.

Anesthetics, Intravenous↗

PubMed1998

Cortical activation states in sleep and anesthesia. II: respiratory reflexes.

Under urethane anesthesia, animals exhibit patterns of cortical activity similar to those seen in wake, drowsiness and slow-wave sleep in unanesthetized animals. In the present study, hypoxic and hypercapnic ventilatory reflexes were examined in unanesthetized and urethane-anesthetized golden mantled ground squirrels in states with similar EEG profiles. Synchronized EEG patterns occurred less frequently in both unanesthetized and anesthetized animals during hypoxic (10% O2) and hypercapnic (5% CO2) exposure. Breathing frequency fell significantly during sleep in animals breathing all gas mixtures, while the relative ventilatory sensitivity to hypoxia and hypercapnia increased during sleep. Urethane-anesthetized animals also showed significant falls in breathing frequency and ventilation and increases in relative ventilatory sensitivity to hypoxia and hypercapnia as they moved into states with synchronized EEG patterns. These data suggest that the brain activity states observed under urethane anesthesia mimic sleep/wake in terms of their effect on respiratory function and that changes in breathing pattern and the enhancement of ventilatory responses in states with a synchronized EEG is not due solely to changes in levels of behavioural stimuli.

Anesthetics, Intravenous↗

PubMed1998

Time domains of the hypoxic ventilatory response.

The ventilatory response to hypoxia depends on the pattern and intensity of hypoxic exposure and involves several physiological mechanisms. These mechanisms differ in their effect (facilitation or depression) on different components of ventilation (tidal volume and frequency) and in their time course (seconds to years). Some mechanisms last long enough to affect future ventilatory responses to hypoxia, indicating 'memory' or functional plasticity in the ventilatory control system. A standard terminology is proposed to describe the different time domains of the hypoxic ventilatory response (HVR) and to promote integration of results from different experimental preparations and laboratories. In general, the neurophysiological and neurochemical basis for short time domains of the HVR (seconds and minutes) are understood better than longer time domains (days to years), primarily because short time domains are studied in the laboratory more easily. Understanding the mechanisms for different time domains of the HVR has important implications for both basic and clinical science.

Acclimatization↗

PubMed1998

Respiratory pattern formation in the isolated bullfrog (Rana catesbeiana) brainstem-spinal cord.

This study characterizes various patterns of motor output obtained from cranial nerves V, VII, X, and XII of in vitro, saline-perfused, brainstem-spinal cord preparations of the American bullfrog (Rana catesbeiana). Motor output indicative of fictive breathing was present in all preparations. In 17 of 26 preparations, fictive breaths were either evenly spaced or randomly distributed, while in the remaining nine preparations fictive breaths occurred in episodes separated by relatively long periods of quiescence. With the exception of fictive breath duration in the non-episodic preparations and the instantaneous frequency of fictive breaths within episodes, all variables associated with fictive breathing were insensitive to changes in perfusion saline pH. In addition to fictive breathing, a large number of other forms of motor output were observed arising from these nerves. While the data suggest that the in vitro preparation is capable of producing a wide repertoire of motor patterns, similar to those seen in vivo, it was difficult, with the current protocol, to reliably produce any single pattern in spite of carefully regulated conditions.

Action Potentials↗

PubMed1997

Do descending influences alternate to produce episodic breathing?

This study examines the episodic breathing patterns of three disparate groups of vertebrates. In an in vitro bullfrog brainstem-spinal cord preparation, episodic breathing was replaced by uniformly spaced breaths following transection caudal to the optic chiasma. The same effect was produced in hibernating squirrels by inhalation of mild anesthesia. Preliminary data suggest that a similar conversion is also produced in hibernating squirrels by vagotomy, in conjunction with blockade of central NMDA-type glutamate receptors. In all cases, even though overall breathing frequency increased, due to elimination of periods of apnea, instantaneous breathing frequency slowed. Seals breathe episodically in sleep and when these animals awaken after the start of a breathing episode, breathing also immediately slows. The data presented here are consistent with the suggestion that in all vertebrates, higher centres can modulate the central rhythm generator for breathing, in both a positive and a negative fashion. During episodic breathing, in the species studied here, these modulating influences alternate in a fashion that produces periods of apnea alternating with periods of relatively high frequency ventilation.

Anesthesia↗

PubMed1997

Role of pulmonary stretch receptor feedback in control of episodic breathing in the bullfrog.

This study compared the "fictive" breathing patterns of decerebrate, paralyzed, unidirectionally ventilated bullfrogs in which pulmonary stretch receptor (PSR) feedback was either absent bilateral vagotomy), maintained constant at different levels (tonic) or oscillated with each fictive breath (phasic) under different levels of hypoxic or CO2-related respiratory drive. Tonic and phasic PSR feedback had identical effects on the fictive breathing pattern; decreasing PSR feedback increased the peak integrated trigeminal electroneurogram recordings and decreased breathing frequency. The effects of bilateral vagotomy and lung deflation to 0 cmH2O on breathing pattern were identical. Although hypoxia (fractional concentration of O2 in air = 0.06) had no significant effect on fictive breathing, ventilating frogs with increasing CO2 levels (fractional CO2 concentration in inspired air range: 0.00-0.03) increased the number of breaths in each fictive breathing episode, and this effect was potentiated by PSR feedback. Whenever respiratory drive was increased, regardless of the method (increase in PSR feedback or chemoreceptor drive), occasional single breaths were replaced by breathing episodes, indicating that the mechanisms responsible for the clustering of the breaths and the onset/termination of breathing episodes are not dependent on either input alone.

Animals↗

PubMed1997

The role of the nucleus isthmi in respiratory pattern formation in bullfrogs.

The nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain located between the roof of the midbrain and the cerebellum. From a neuroanatomical perspective, the NI can be compared with the pons which, in mammals, contributes to the control of breathing pattern. This study tested the hypothesis that the NI plays a critical role in breathing pattern formation in the bullfrog. More specifically, we postulated that this nucleus was the site responsible for clustering breaths into distinct episodes of breathing. This hypothesis was tested by comparing the respiratory motor output of decerebrate, paralyzed and artificially ventilated bullfrogs before and after bilateral lesions of the NI by pressure microinjections of lidocaine or kainic acid (KA) into this area. Bilateral microinjections of lidocaine or KA into the NI transformed the breathing pattern from episodic (many breaths per episode) to one of evenly spaced single breaths, without affecting the amplitude of the fictive breaths. These changes in breathing pattern were associated with an overall decrease in breathing frequency and a reduction in CO2-chemosensitivity. Breathing episodes of more than one breath reappeared during hypercarbia (3.5% CO2 in air) after KA lesioning. Bilateral lesions to the NI did not affect the changes in the timing or the amplitude of the respiratory-related bursts elicited by pulmonary stretch receptor feedback, indicating that mechanoreflexes do not require NI input. We conclude that the NI is not responsible for the genesis of breathing episodes, but provides a tonic excitatory input to respiratory centers in the lower brainstem. The NI also plays an important role in either CO2 chemodetection or, more probably, integration of CO2 chemoreceptor information. This, in turn, contributes to the production of episodes of more than one breath.

Afferent Pathways↗

PubMed1995

Cardio-ventilatory control in rainbow trout: II. Reflex effects of exogenous neurochemicals.

The effects of various neurochemicals were examined in intact, unanesthetized rainbow trout (Oncorhynchus mykiss) to assess the role of branchial O2-sensitive chemoreceptors in the cardio-ventilatory responses to exogenous neurochemicals. cyanide stimulated ventilation and elicited bradycardia when give externally but only stimulated ventilation when injected internally. Norepinephrine increased heart rate, blood pressure and ventilatory rate but opercular pressure was not affect. Dopamine had no effect on either heart or ventilatory rate but increased blood pressure and decreased opercular pressure. Serotonin stimulated heart rate and ventilation but decreased blood pressure. Acetylcholine and nicotine stimulated all cardio-ventilatory variables. Muscarine decreased heart rate and blood pressure and had a biphasic effect on ventilation. These results, combined with the results from the preceding study, suggest that the cardio-ventilatory effects of exogenously administered (1) cyanide are entirely mediated by gill O2 receptors, (2) serotonin, and cholinergic drugs could be partly mediated by O2 receptors and (3) catecholaminergic drugs are not mediated by O2 receptors.

Animals↗

PubMed1995

Pulmonary mechanics of hibernating squirrels (Spermophilus lateralis).

In this study we examined the effects of hibernation on several aspects of pulmonary mechanics in golden mantled ground squirrels. Measurements were made on anesthetized animals that were active in late fall (FA, n = 7), maintained at 23 degrees C and normal photoperiod in mid-winter (WA, n = 0) and hibernating at 5 degrees C in mid-winter (H, n = 8). Compared with FA animals, WA animals showed an increase in inspiratory reserve volume (IRV) and in inspiratory, vital and total lung capacities (IC, VC, and TLC). Hibernating animals exhibited further increases in IRV, IC, VC and TLC, an elevated residual volume, and virtual elimination of the expiratory reserve volume. There was also a decrease in specific lung compliance and a sharp knee in the lower portion of the quasi-static volume-pressure curve. There was a significant increase in the elastic work required to ventilate the hibernating animals compared with FA animals. The data suggest that, despite an increase in compliance at TLC, there is decreased compliance at low volumes, gas trapping at functional residual capacity, and an increase in the work required to breathe in hibernating animals.

Animals↗

PubMed1995

Characteristics of diaphragm muscle fibre types in hibernating squirrels.

Muscle samples from the diaphragms of 7 full-awake (FA), 10 winter-awake (WA), and 8 hibernating (H) squirrels (Spermophilus lateralis) were quick frozen, sectioned and processed for NADH-TR reaction end-product and myofibrillar-ATPase. Both WA and H squirrels showed small increases in diaphragm weight, reductions in body weight, and hence, significant increases in the diaphragm weight to body weight ratio compared to FA squirrels. They also showed increases in muscle fibre type cross-sectional areas and in the oxidative capacity of type 2b fibres as well as a reduction in capillary density. Furthermore, there also was an increase in the proportion of type 2b fibres in the diaphragm of the H squirrels. Thus, despite the dramatically reduced ventilation associated with hibernation, H squirrels exhibited (1) hypertrophy of the diaphragm which may represent an adaptive response that enables them to work against a stiffer chest wall, and (2) an increased oxidative capacity which enables them to fuel this with fat.

Animals↗

PubMed1995

Cardio-ventilatory control in rainbow trout: I. Pharmacology of branchial, oxygen-sensitive chemoreceptors.

The effects of various neurochemicals on O2-sensitive chemoreceptor afferent discharge in the glossopharyngeal nerve (cranial nerve IX) were examined in an isolated, perfused first gill arch preparation from rainbow trout. Afferent neural activity from O2 receptors in the first gill arch increased in response to hypoxic perfusate and NaCN. Adrenergic agonists (epinephrine, norepinephrine and isoproterenol) had little effect on neural activity. Dopamine and 5-hydroxytryptamine (serotonin) caused a brief, small burst in chemoreceptor activity followed by a mild inhibition of receptor discharge. Acetylcholine and nicotine were potent neurochemical stimulants; muscarine had only a slight effect. While atropine completely blocked the effects of acetylcholine on receptor discharge, it only slightly inhibited responses to hypoxia and NaCN. Thus, although cholinergic mechanisms appear more likely than either adrenergic or serotonergic mechanisms to alter cardiovascular and ventilatory reflexes in fishes through their effects on O2-sensitive chemoreceptor activity, the transduction process involved in O2-chemoreception appears to be complex and not dependent on any single one of the neurochemicals tested.

Adrenergic Antagonists↗

PubMed1995

Parasympathetic influence on heart rate in euthermic and hibernating ground squirrels.

The relative role of the parasympathetic nervous system during deep hibernation is enigmatic. Conflicting hypotheses exist, and both sides draw support from investigations of vagal influence on the heart. Recent studies have shown cardiac chronotropic and inotropic effects of parasympathetic stimulation and inhibition in isolated hearts and anesthetized animals at hibernating body temperatures. No studies, however, have demonstrated such occurrences in undisturbed deeply hibernating animals. The present study documents respiratory-related alterations in heart rate during euthermia and hibernation at ambient temperatures of 15, 10 and 5 degrees C mediated by parasympathetic influence. During quiet wakefulness, euthermic squirrels breathed continuously and exhibited a 29% acceleration in heart rate during inspiration. During deep undisturbed hibernation, at 15, 10 and 5 degrees C ambient temperature, animals exhibited an episodic breathing pattern and body temperatures were slightly above ambient temperature. At each temperature, heart rate during the respiratory episode was greater than that during the apnea. The magnitude of this ventilatory tachycardia decreased with ambient temperature, being 108% at 15 degrees C, 32% at 10 degrees C and 11.5% at 5 degrees C. Animals exposed to 3% CO2 at 5 degrees C, which significantly increased ventilation, still exhibited an 11.7% increase in heart rate during breathing. Thus, the magnitude of the ventilation tachycardia was independent of the level of ventilation, at least over the range studied. Inhibition of vagus nerve conduction at 5 degrees C was achieved using localized nerve block. This led to an increase in apneic heart rate and abolished the ventilatory tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗