Cardiovascular And Respiratory Control Mechanisms During -PDF Free Download


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As the cardiovascular and respiratory systems more slowly begin to attain a steady-state response profile (phase 2), each physiological system comes increas-ingly under the influence of further neural and humoral feedback control mechanisms and central neural reverberation. These feedback mechanisms may

The cardiorespiratory responses to the onset of mild or moderate exercise
phase 1 are rapid 0 15 s in fact so rapid that purely neural control mechanisms
are probably responsible for the initial actions of the various physiological
systems As exercise proceeds 15 s to 2 or 3min slower increases in the
cardiorespiratory variables occur phase 2 until a new steady state is reached
phase 3 3 min onwards Neural and humoral control mechanisms now combine
to bring about an appropriate response Fig 1
The two most important neural control systems responding during phase 1 are
1 mechanical feedback reflexes originating from the active muscle mass and 2 a
centrally generated feedforward motor pattern In addition there may also be a
non neurally mediated cardiodynamic feedforward mechanism also operating
during phase 1 which could couple an increase in ventilation to an increase in
cardiac output
As the cardiovascular and respiratory systems more slowly begin to attain a
steady state response profile phase 2 each physiological system comes increas
ingly under the influence of further neural and humoral feedback control
mechanisms and central neural reverberation These feedback mechanisms may
arise either from neural afferent inputs originating in the lungs the heart the
carotid body and muscle chemoreceptors the arterial baroreceptors and thermor
eceptors or from humoral inputs blood borne substances acting directly on the
central nervous system or indirectly via peripheral receptor systems Furthermore
the control mechanisms predominant during phase 1 may still be operative
during phase 2 During the steady state phase 3 further prolonged exercise may
be compromised by thermoregulatory and fluid homeostatic control mechanisms
as well as changes in substrate utilization and delivery There may also be
modulation brought about by an array of hormones or other chemical substances
This review will describe the way in which each phase of physiological
adjustment to exercise is controlled and coordinated The intention is to produce
an up to date synthesis of recently obtained evidence of these control mechanisms
and then to discuss how they may be integrated into an overview of control
mechanisms operating during exercise
Control mechanisms operating during phase 1
The century old concept of a neural control mechanism operating during all
three phases of exercise commonly known as the exercise reflex has been
attributed to the German physiologist Zuntz Rowell 1986 Although numerous
addenda and modifications have been made the major core of the concept
remains intact Simply the reflex would be initiated within the active muscle mass
by a build up of metabolites due to a mismatch between perfusion and muscle
metabolism Chemoreceptors of some kind would sense this imbalance and the
increased firing rate in the chemosensitive afferent nerves would be detected in the
Control mechanisms during exercise 311
Fig 1 The cardiorespiratory responses to moderate sub maximal cycling exercise in
humans Phase 1 lasts about 15 s from the onset of exercise phase 2 lasts for another
2 3 min followed by a steady state phase 3 Recovery from exercise has qualitatively
similar periods of adjustment modified from Wasserman et al 1986
central nervous system and as a result the inadequacy of blood flow within the
muscle would be registered The appropriate increases of for example venti
tion central and peripheral components of perfusion and blood pressure would
be activated by the efferent arm of the reflex arc namely the autonomic
Table 1 Possible control mechanisms operating during exercise
Neurally mediated
1 Muscle receptor reflexes
2 Supramedullary command
3 Cardiopulmonary mechanoreceptor reflexes
4 Baroreceptor reflexes
5 Chemoreceptor reflexes
Non neurally mediated
1 Cardiodynamic coupling
2 Cardiac Starling mechanism
3 Lung heart mechanical pumping assistance
4 Heart lung mechanical pumping assistance
Neurohumorally mediated
1 Decreased O2 partial pressure
2 Increased CO2 production
3 Increased H production
4 Increased temperature
5 Increased catecholamine production
6 Increased potassium release
Long term modulation
1 Hormonal and opioid release
2 Exercise training
3 Other competing stresses
nervous system This would result in a restoration of the metabolite concentrations
to normal levels The muscle chemoreflex has been implicated in the exercise
reflex since the 1930s in the pioneering work of Alam and Smirk 1937 up to the
present day for example in McArdle syndrome patients Lewis etal 1991
primarily because of the undisputed existence of chemosensitive nerve fibres that
originate in the muscle and act upon the medullary cardiorespiratory control
centres in the brainstem Mitchell and Schmidt 1983 In the context of phase 1
control the proven existence of mechanosensitive nerve fibres originating from
muscles is also particularly relevant
There is a growing body of direct and circumstantial evidence that for example
increases in ventilation heart rate and blood pressure can be elicited to a degree
even when the muscle chemoreflex is partially or wholly inoperative Hobbs 1982
Eldridge et al 1985 Galbo et al 1987 Eldridge and Waldrop 1991 This evidence
has led to the belief that supramedullary brain centres can confer a strong central
command primarily locomotor in nature which may also interact with respiratory
and cardiovascular control centres in the brainstem Krogh and Lindhard 1913
1917 The result would be a cardiorespiratory response that is more or less
matched to the intensity of muscular activity and needed only fine continual
adjustment from the myriad of peripheral neural and neurohumoral receptor
mechanisms as exercise proceeded
A third completely different mechanism has been proposed for the linking o
Control mechanisms during exercise 313
tatantaneous increases in cardiac output and ventilation during phase 1 The idea
of a cardiodynamic coupling involves the direct activation of ventilation by a
signal from the heart itself or from within the blood flowing from it This may be
either chemical or mechanical Whipp and Ward 1982 Wasserman etal 1986
These three control mechanisms constitute the main methods by which the initial
fast component of cardiovascular and respiratory responses can be activated
during exercise Other non neural mechanisms may play minor roles
Neural mechanisms
Muscle sensory afferent fibres
The most important prerequisite for demonstrating a reflex neural control
system that arises within the skeletal muscle mass is the presence of afferent
sensory neurones There are four groups of sensory afferent nerves that arise from
muscle classified by roman numerals I IV Groups I III have nerve fibres with a
myelin sheath whilst group IV afferent nerves have nerve fibres that are non
myelinated Group I and II nerve fibres are relatively large in diameter generally
between 6 and 20 im with conduction velocities of more than 30ms 1 They
originate from within the muscle spindles where sensory endings are either
primary i e annulospiral endings in spindles or innervating Golgi tendon organs
mainly group I or secondary i e sensory endings on the intrafusal fibres mainly
group II Group I and II nerve fibres do not have a systematic important role in
chemoreception or cardiorespiratory control Kaufman et al 1982 Waldrop et al
1984 and so will not be dealt with further in this review Group III and IV nerve
fibres are both thin between 1 and 6 im in diameter with correspondingly slower
conduction velocities 15 m s 1 than group I and II nerve fibres Most group III
and all group IV endings terminate as free nerve endings or as more recently
suggested unencapsulated nerve endings in the musculature Group III nerve
endings seem to be associated with collagen structures in the skeletal muscle
whilst the endings of group IV afferent nerves are more often associated with
blood and lymphatic vessels von During et al 1984 This anatomical distinction is
indicative of mechanoreceptive group III or chemoreceptive group IV func
tions Mitchell and Schmidt 1983
Within group III and IV nerve afferents there are nerve fibres that have
receptors sensitive to non noxious stimuli such as muscular contraction or
movement local touch pressure and tendon or muscle stretch Kaufman et al
1988 Stebbins etal 1988 These units have a low stimulus threshold are
commonly known as ergoreceptors and make up about 65 of group III
afferents and 45 of group IV afferents The remaining units in both groups are
particularly sensitive to more noxious stimuli and are thus commonly termed
nociceptors These units have a high stimulus threshold to mechanical distortion
and to chemical and thermal stimuli some even showing polymodal receptive
characteristics Kaufman etal 1988 Chemical stimulants include potassium
Rcreased pH bradykinin and arachidonic acid Kaufman etal 1988 Stebbins
Fig 2 The firing activity recorded from group III A and group IV B D fine
muscle afferent fibres in response to an induced muscular contraction lasting 40 45 s
filled bar and columns B and C represent the activity in two group IVfibresand D
represents the activity in a group IV afferent fibre whilst the muscle was kept
ischaemic before and during an induced contraction Note the instant strong response
of the group III fibre and also its rapid adaptation compared to the sustained weaker
response of the group IV fibres redrawn from Mitchell 1990
et al 1990 During exercise all of these stimuli may be present within the
receptive fields of the group III and IV nerve fibre endings and thus elicit a change
in afferent nerve firing rate
The immediate onset and rapid recovery of group III afferent activity during
induced muscular contraction is functionally consistent with a predominantly
mechanoreceptor function whilst the slower onset and more sustained activity
within group IV afferent units is functionally consistent with a more chemorecep
tive function Muscle ischaemia caused by upstream arterial occlusion or
increased intramuscular pressure during isometric contraction seems to stimulate
further the firing rate of afferent fibres during exercise Fig 2
There is ample evidence suggesting that the group III and IV muscle afferent
are heavily involved in the cardiovascular responses during all phases of exercis
Control mechanisms during exercise 315
increase in firing rate elicits an increase in blood pressure heart rate and
contractility as well as a significant and subtle redistribution of blood flow towards
the working muscle heart in cats at least and selected areas of the brain but
away from the kidneys McCloskey and Mitchell 1972 Mitchell et al 1977
Crayton et al 1979 Waldrop and Mitchell 1985 a pattern similar to that seen in
conscious exercising animals and humans Rowell 1986 Musch et al 1987
Armstrong 1988 Butler et al 1988 When most of the increase in afferent
information is blocked by dorsal root section the cardiovascular responses in
particular to muscular contraction are attenuated or abolished in anaesthetized
animals McCloskey and Mitchell 1972
The evidence for the role of muscle afferent input in eliciting the increase in
ventilation is not quite so compelling as it is for activation of the cardiovascular
system Certainly ventilation does increase and total pulmonary resistance is
reflexly decreased during electrically induced muscular contraction McCloskey
and Mitchell 1972 Bennett 1984 Rybicki and Kaufman 1985 and partial spinal
cord ablation in conscious ponies significantly attenuates the initial hyperpnoea
during phase 1 of low level voluntary exercise Taken together this evidence
implies at least some role for muscle afferent feedback in the control of ventilation
Pan et al 1990 However ventilation still increases in proportion to metabolic
rate during electrically induced muscular contraction in patients and anaesthetized
animals with complete spinal cord lesions where all sensory muscle afferent input
is presumably lost suggesting that muscle afferent information is not involved in
the ventilatory responses to exercise Cross et al 1982a Adams et al 1984 Brice
et al 1988 Muscle mechanoreceptor afferent information may contribute to the
linkage between respiratory frequency and locomotory gait which has been shown
to be present in several species during exercise Bramble and Carrier 1983
Group III and IV afferent nerves enter the spinal cord mainly through the dorsal
roots and disseminate throughout the dorsal horn of the segment of entry and also
neighbouring segments making synaptic connections with a group of spinal
neurones in laminae I V of the spinal cord the dorsal column nuclei and directly
in the nucleus tractus solitarius Kalia et al 1981 which together form part of a
pathway leading to integrative areas of the brain Suggested ascending neural
spinal pathways illuminated for example by retrograde horseradish peroxidase
labelling or lesioning include the lateral funiculus tract Kozelka et al 1987 and
spino thalamic and spino reticular tracts Putative neurotransmitters or neuro
modulators at the first synaptic relay point in the reflex arc include both substance
P and somatostatin Kaufman et al 1988 the release of which may be modulated
by opiates Hill and Kaufman 1990 acting at opiate receptor sites on the afferent
nerves Pomeroy et al 1986 In the central brain areas the spinal neurones
furnish information to a number of important regions of cardiorespiratory control
including the lateral reticular nucleus Ciriello and Calaresu 1977 Iwamoto et al
1984 and possibly the cells of the lateral tegmental field which are both within the
u d a l ventrolateral region of the medulla Bauer et al 1990 Iwamoto et al 1989
Thus the muscle afferent nerve fibres can be structurally and functionally
identified from their origin in the collagen matrix and in the blood and
vessels of the muscle through the spinal cord to their target brainstem areas and
the nuclei involved in eliciting the appropriate cardiovascular and respiratory
responses to muscular contraction
Central command
The evidence that afferent input can originate from supramedullary centres of
the central nervous system interact with medullary neurone pools and have an
influence on physiological responses to exercise in man is mainly circumstantial
Recent advances have been made in functionally dissecting central afferent input
from peripheral afferent input for example from muscle chemoreflexes using
partial neuromuscular blockade Concurrently in anaesthetized or decerebrate
animals lesion and or stimulation of putative nuclei conferring or relaying a
central command have also led to a significantly better understanding of the
complex central afferent command
Experiments involving human exercise The basic experimental protocol for
establishing the existence of the central component of the exercise response of
the cardiovascular system in particular heart rate and blood pressure is as
follows During partial neuromuscular blockade for example with tubocurarine
muscle isometric strength is reduced so that to obtain the same absolute isometric
force production there must be a greater central motor drive or effort Leonard
et al 1985 Locomotion respiration and cardiovascular responses can all be
elicited in parallel by stimulation of the central motor centres Eldridge et al
1985 Therefore after partial neuromuscular blockade the increases in central
motor drive lead to greater increases in the cardiorespiratory variables than in the
control muscle contraction Fig 3 In this experimental condition the chemical
milieu of the contracting muscle is the same and is not therefore correlated to the
increases in ventilation heart rate and blood pressure When the same subjects
produced a contraction that represented the same relative proportion of in the
first instance the control maximal voluntary contraction MVC and in the
second instance the MVC measured during partial neuromuscular blockade the
central command was the same but the absolute force production and by
inference the muscle afferent information was less in the blocked state Heart rate
and blood pressure increased to the same extent in the non blocked and blocked
state i e were correlated to central command and not to the chemical milieu
existing in the contracting muscle and thus not to the neural activity of muscle
chemo and mechanosensors Mitchell 1990 The role of central command in
eliciting both locomotor and cardiovascular responses by parallel activation during
exercise is represented schematically in Fig 4
Recently heart rate and blood pressure have been shown to recover at different
rates after a subject has performed a powerful MVC If blood flow is occluded at
the end of the contraction heart rate returns to resting levels very quickly In
contrast blood pressure decreases to a level that is still significantly higher tha
that at rest and remains there until the occlusion is relieved The interpretation
Control mechanisms during exercise 317
0 1 2 3 4 5 0 1 2 3 4 5
Fig 3 The effect of partial neuromuscular blockade on heart rate and blood pressure
responses to static exercise In A the same absolute force is maintained without filled
curve or with open curve neuromuscular blockade whereas in B the same relative
percentage of the measured maximal voluntary contraction force is maintained without
filled curve or with neuromuscular blockade open curve See text for an
interpretation of these findings redrawn from Mitchell 1990
this finding is that heart rate is increased mainly by increased central command or
muscle mechanoreceptors via vagal withdrawal whereas blood pressure is
increased in part by central command and muscle mechanoreceptor feedback but
also in part by increased afferent input from muscle chemoreceptors sensing a
build up of metabolites during the MVC trapped in the muscle by occlusion
Fig 5 When an attempted contraction is performed during neuromuscular
blockade the build up of metabolites is not enough to stimulate the muscle
chemoreceptors and so blood pressure rapidly returns to normal even during
occlusion Rowell and O Leary 1990 The increases in blood pressure and heart
rate in response to moderate intensities of static contraction or dynamic contrac
tion when there is little or no build up of metabolites must be elicited primarily
by central command or muscle mechanoreceptors Gandevia and Hobbs 1990
Heart rate appears to be controlled more by central command via vagal
withdrawal and increased sympathetic drive than by muscle mechanoreceptors
during all intensities of static contraction Victor et al 1989 Hypnotic suggestion
has been used to increase the perception of muscular effort during a muscular
contraction and can lead to a hyperventilation Morgan et al 1973 This finding
agrees with the evidence concerning the role of central command in determining
the cardiovascular responses to exercise Evidence exists that the heart rate
sponse to exercise can be attenuated by behavioural conditioning Talan and
K lgel 1986 Perski et al 1985 The implication of this is that when the muscle
Motoneurone Light load
non blocked
Heavy load
U UA non blocked
Light load
Blockade blocked
Vt A A A A i
Fig 4 A hypothesis in which descending central motor command activates in
parallel a recruitment of musclefibresand an appropriate cardiorespiratory response
be it blood pressure heart rate or ventilation The cardiorespiratory response is graded
to the degree of muscular contraction in the non blocked state However during
neuromuscular blockade the cardiorespiratory response is apparently stronger than the
muscular response This is due to a larger central motor command being necessary to
maintain the force production of the muscle mass adapted from Hobbs 1982 and
redrawn from Rowell 1986 Filled symbols represent active motoneurones and
muscle fibres unfilled ones represent inactive ones
afferent input is constant same absolute workload some cerebral influence on
the central motor command can still occur
Experiments involving electrical or chemical lesions and stimulation Obviously
the limitation of the experimental protocols described previously is that they offer
purely circumstantial evidence of a functional central command but they offer no
information about its anatomical location Traditionally the search for the
anatomical loci conferring the functional central afferent command has followed
two lines of enquiry First areas suspected of being involved in originating a
command can be rendered non functional by coarse or as techniques become
available fine lesion be it surgical or chemical Second those same areas can be
stimulated electrically or chemically and the consequent physiological responseji
monitored Spyer 1990
Control mechanisms during exercise 319
Fig 5 The partitioning of importance of central motor command muscle mechano
receptors and muscle chemoreceptors in bringing about a response in blood pressure
upper panel and heart rate lower panel during a muscular contraction filled bars
with B or without A neuromuscular blockade Arterial occlusion is initiated at the
end of the 3 min contraction to trap any released metabolites within the muscle In the
unblocked state blood pressure does not fall back to resting levels immediately after
the contraction because muscle chemoreceptor activation by metabolites maintains a
pressor reflex even in the absence of central command and muscle mechanoreceptor
control The muscle chemoreceptors do not appear to maintain an elevated heart rate
In the blocked state an attempted contraction does not produce a large enough build
up of metabolites to stimulate muscle chemoreceptors significantly and therefore
blood pressure falls rapidly back to resting levels during occlusion redrawn from
Rowell and O Leary 1990
The many nuclei within the central nervous system that have direct or indirect
influences on the cardiorespiratory centres in the medulla also have many
interconnections among themselves This makes unravelling individual roles for
each nucleus extremely difficult and any lesion or stimulation of one nucleus will
inevitably have repercussions for neural activity originating from other nuclei
Nevertheless a number of experiments has highlighted the importance of a large
number of brain areas The lesion of neurones in the subthalamic area of the brain
in primates has been shown to eliminate the increase in blood pressure during
exercise This finding implies that the descending command from the motor
cortex principally responsible for driving an orchestrated set of muscle fibre
contractions necessary for example during walking also sends a parallel drive to
cardiorespiratory control centres in the medulla Fig 4 Hobbs 1982 When the
intact subthalamic locomotor region is electrically or chemically stimulated in
unanaesthetized animals increases in ventilation blood pressure and heart rate as
d ell as a redistribution of blood flow can be elicited Similar responses can be
Jncited in animals that are deeply anaesthetized or paralysed and which obviously
do not walk DiMarco et al 1983 Eldridge etal 1985 Waldrop etal 1986a
addition to the subthalamic locomotor region the neighbouring brain area known
as the fields of Florel can elicit when directly stimulated substantial increases in
blood pressure and heart rate coupled with increased phrenic nerve activity and a
bronchodilator response Together these two anatomically distinct regions have
been regarded as the main location for the functional central command Eldridge
et al 1985 McCallister et al 1988 Rybicki et al 1989 Interestingly lesions in the
fields of Florel do not alter the cardiorespiratory responses to running in conscious
dogs Ordway et al 1989 Thus merely abolishing the role of one important site
will not necessarily compromise the overall pattern of central neural feedforward
command or the resultant efferent outflow and pattern of responses This implies a
degree of redundancy or neural plasticity Superimposed on the drive from these
nuclei is the influence of the defence arousal system The perifornical region of the
hypothalamus and particularly the amygdala forms a functional centre receiving
projections from the hippocampus forebrain and brainstem summarized in
Spyer 1984 Efferent projections connect the hypothalamic defence area with the
medullary cardiorespiratory control areas Hilton 1982 Spyer 1990 and may
also relay information via the nucleus reticularis gigantocellularis Richard et al
Cardiopulmonary mechanoreceptor afferent information
Afferent fibres from the cardiopulmonary region course with the vagus nerve
towards the brain or alternatively with the sympathetic nerves which enter the
spinal cord Vagally mediated mechanoreceptors which have receptive fields in
the four chambers of the heart and also in the pulmonary artery are responsive to
distension brought about by the increase in end diastolic volume in the atria and
ventricles that may occur during exercise Plotnick et al 1986 or increased atrial
or pulmonary artery pressure Their activation could lead to a reduction in heart
rate and so would function as a peripheral feedback mechanism during exercise
However experimentally increased pulmonary artery pressure during maximal
exercise in humans did not result in any change in cardiac output heart rate or
ventilation D L Turner H Hoppeler C Noti H P Gurtner H Gerber and
G Ferretti in preparation nor did experimentally raised right ventricular
pressure in the anaesthetized dog Crisp etal 1988 Patients with denervated
heart and lungs through transplantation or cardiac denervated goats still demon
strate an appropriate ventilatory response to exercise but not an adequate
cardiovascular response Banner etal 1988 Brice et al 1991 Blocking of
sympathetically mediated information by removal of the left stellate ganglion does
not lead to major changes in cardiovascular responses to exercise apart from
possibly changing the distribution of blood flow across the myocardial wall Stone
1983 Thus cardiac receptors probably at most only play a minor role during
exercise in normal environmental conditions Incidentally during exercise wit
peripheral pooling of blood for example brought about by lower body negati
Control mechanisms during exercise 321
e s s u r e cardiopulmonary mechanoreceptor afferent information may play a role
in maintaining blood pressure Mack etal 1990
The effect of chronic or acute hilar nerve section with a consequent loss of lung
volume afferent feedback to the medullary centres has been studied in dogs and
ponies Minute ventilation is not affected although the pattern by which it is
maintained may be altered Flynn et al 1985 Clifford et al 1986 This is similar to
the role ascribed to lung mechanoreceptors in exercising humans Lind and
Hesser 1984 Irritant or rapidly adapting receptors and J receptors also convey
afferent information via the pulmonary vagal nerves the former potentially
facilitating respiration during exercise The latter stimulated by pulmonary
congestion or oedema are situated in the alveolar wall and could potentially have
an important role during extreme exercise when pulmonary oedema is thought to
occur O Brodovich and Coates 1991 Neither appear to have a role in
controlling ventilation following vagotomy but again may be more important in
controlling the respiratory pattern Recently the ventilatory response to exercise
has been shown to persist even after heart or heart lung transplantation i e
cardiac or cardiopulmonary deafferentation and again indicates a relatively small
role for cardiopulmonary receptor control mechanisms during exercise
Baroreceptor afferent information
Recent evidence suggests that during exercise the baroreflex is reset to a higher
operating level during phase 1 as a result of a central command impinging upon the
baroreflex neuronal pool in the medulla Ludbrook 1983 Mitchell etal 1983
Rowell 1986 The maintenance of blood pressure at this new higher level is still
however adequately controlled by the reflex involving carotid sinus and aortic
baroreceptors and cardiac output and vascular resistance even during severe
exercise see later Rowell and O Leary 1990 Cardiac output is unaffected by
baroreceptor isolation in exercising dogs less afferent input with maintenance of
adequate blood pressure due to increased vascular resistance Walgenbach and
Donald 1983 During severe exercise this may even occur in the active muscle
Rowell and O Leary 1990
Chemoreceptor afferent information
During phase 1 of exercise the delay between measurable changes or errors in
the levels of blood gases and blood borne metabolites occurring in the contracting
muscles and their reception in peripheral or central arterial chemoreceptors
precludes a role of these receptive sites in initiating cardiorespiratory responses
However in humans relatively hypoxic and hypercapnic blood has been shown to
reach the pulmonary artery at the onset of exercise as a bolus from the inferior
vena cava before any return of venous blood from the exercising leg muscle
Casaburi etal 1989 The functional significance of this has yet to be fully
Pbtermined The central chemoreceptors have been ruled out as an important
source of afferent input in the control of ventilation or circulation in all phases
exercise Casey etal 1987
Non neural mechanisms
An entirely different approach to the possible control of coupled cardiorespira
tory responses during exercise has been proposed The cardiodynamic coupling
hypothesis involves a direct linkage between cardiac output and ventilation
consisting of some kind of feedforward mechanism by which a pulmonary
circulatory stimulus or stimuli activates an increase in ventilation There is a
large body of evidence that lends circumstantial support to this hypothesis
Wasserman et al 1974 found that ventilation rose immediately and in proportion
to an induced increase in cardiac output Owing to the time delays between the
pulmonary artery and peripheral and central chemoreceptors the rise in venti
lation could not be mediated by a chemoreflex from these receptors In addition
in humans with resected carotid bodies cardiodynamic coupling is still present
during phase 1 of exercise Wasserman et al 1975 The activating stimulus for an
increase in ventilation secondary to an increase in cardiac output may be a
mechanical signal arising from distension of the right atrium and ventricle or even
the pulmonary artery Thus when stroke volume is increased for example by
increasing right ventricular work as a result of altered peripheral resistance and or
venous return ventilation increases accordingly and with the appropriate time
course Jones etal 1982 Incidentally altering heart rate only for example by
increasing the output of an artificial pacemaker does not affect ventilatory
responses to exercise Jones etal 1981 However the occurrence of this
feedforward cardiodynamic mechanism has been seriously questioned in studies of
exercising ponies Pan etal 1983 1984 and humans Adams etal 1987 Turner
et al 1991 and also in isolated subsystems involving the heart pulmonary arteries
and lungs Lloyd 1984
Stretching of the walls and therefore muscle fibres of the heart by an increase
in venous return may at least during mild exercise lead to an increase in stroke
volume and thus cardiac output via the Frank Starling mechanism Plotnick
et al 1986 The role of heart lung and lung heart mechanical pumping assistance
due to physical movement during exercise is potentially of importance but as yet
has not been thoroughly investigated Agostoni and Butler 1991 These two
mechanisms could occur without neural or neurohumoral involvement
Control mechanisms operating during phases 2 and 3
The neurohumoral drive
Phase 1 only lasts for a few seconds after which there is a slower increase in a
number of cardiorespiratory variables towards an asymptotic level Fig 1 The
phase 2 and 3 periods can obviously still be under the control of the mechanisms
operating during phase 1 However their delayed onset coincides roughly with t
delay for blood borne chemical transfer from muscles to heart pulmona
Control mechanisms during exercise 323
lungs carotid bodies and cerebral circulation Thus phases 2 and 3 have
long been associated with a number of possible humoral mediators of the
cardiorespiratory exercise responses The original synopsis of the two stage
neurohumoral control mechanism during exercise was popularised by Dejours
1964 Humoral mediators can conceivably work directly upon target organs for
example the heart smooth muscle of the lungs or medullary centres or indirectly
via peripheral chemoreceptors from which neural pathways mediate control
Flandrois 1988
Humoral mechanisms
There are many possible candidates for the all important chemical blood borne
mediator that may arise from the active muscle mass during exercise Increased
partial pressure or content of carbon dioxide decreased oxygen partial pressure
increased hydrogen ion concentration increased temperature increased catechol
amine concentrations and increased potassium concentration are all potential
signals that exist during exercise
Mixed venous chemoreceptors
During phase 3 of exercise there is a large increase in carbon dioxide flow
cardiac output x mixed venous carbon dioxide content to the heart and lungs
When the flow of carbon dioxide is decreased in non exercising humans
ventilation also decreases indicating a potentially strong direct role for carbon
dioxide flow in ventilatory control Dolan et al 1981 When the carbon dioxide
flow to the lungs during exercise is altered by removing or adding carbon dioxide
using a gas exchanger increased carbon dioxide flow is associated with an increase
in ventilation Wasserman et al 1986
There is possibly a vagally mediated pulmonary chemosensitivity to an increase
in carbon dioxide that may be an indirect humoral activator of ventilation during
exercise Green and Sheldon 1983 although other studies have shown that lung
denervation does not alter the total ventilatory response only the pattern by
which it is achieved Clifford et al 1986 Favier et al 1982 Unfortunately there
appears to be very little evidence suggesting the existence of mixed venous or
pulmonary arterial chemoreceptors and so their role as part of an indirect
Immorally activated reflex during exercise can be considered negligible Wasser
man et al 1986 Indeed the increases in venous carbon dioxide concentration and
ventilation can be disassociated by occlusion of the thigh during cycling exercise
Stanley et al 1985
Arterial chemoreceptors
During steady state exercise phase 3 arterial oxygen and carbon dioxide
partial pressures and pH are all maintained at normal levels and there will be no
mean increase in stimulus to the carotid body or central chemoreceptors Thus
hen the carotid body chemoreceptors are surgically resected in some humans
ventilatory responses during phase 3 are the same as those in normal

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STATE OF HEALTH IN THE EU: COUNTRY HEALTH PROFILE 2017 – FRANCE Health in France . 3 (Number of deaths: 277 141) Women (Number of deaths: 282 485) Men Cardiovascular diseases Cancer Nervous system (incl. dementia) External causes Other causes Respiratory diseases 23% 33% 7% 6% 7% 12% 24% 27% 25% 23% 8% 5% Note: The data are presented by broad ...

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Prevention and control of noncommunicable diseases in the ...

Prevention and control of noncommunicable diseases in the ...

Prepared for the Ministry of Health of the Philippines by World Health Organization United Nations Development Programme 2019 . Abstract Noncommunicable diseases (NCDs) such as cancer, cardiovascular disease, diabetes and chronic respiratory diseases and their risk factors are an increasing public health and development challenge in the Philippines. This report provides evidence through three ...

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LAB 5 - Bluegrass Community and Technical College

LAB 5 - Bluegrass Community and Technical College

LAB 5 ANATOMY OF THE RESPIRATORY, DIGESTIVE, AND URINARY SYSTEMS Assignments: Due before lab: Quiz: Complete the car. diovascular case studies (page 48). Label diagrams of respiratory, digestive and urinary models (pages 55-65). Due next lab: Lab Exam I – covers labs 1 through 4, the Interactive Physiology CD ROM exercises, and the . cardiovascular case studies. Summer Classes: In the summer ...

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FLOWSHEET 8. Page 4 of 9 TOTAL PEDIATRIC EARLY WARNING SYSTEM (PEWS) SCORE: a. To obtain a total PEWS score, ADD the category scores together (respiratory + cardiovascular + behaviour + vomiting + bronchodilator = maximum achievable score of 13). b. CALCULATE and RECORD total PEWS score with every set of vital signs. PLEASE NOTE if PEWS score ...

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