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Regulation of the Heart's Functions
By ROBERT F. RUSSHMER, M.D.
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THE SIGNIFICANCE of cardiovascular
regulation extends beyond considerationis
of normal function and control. Primary derangements of various cardiovascular control
mechanisms represent an important and perplexing group of disease entities confronting
the physician in his daily practice. The various types of regulating mechanisms being
discussed in this symposium constitute a rational classification of those clinical problems
that are produced by distortion or abnormalities of control. For example, abnormal control
of heart rate is involved in the extravagant
tachyeardia that occurs with neurocirculatorv
asthenia and other manifestations of psychologic instability. Both primary and secondary
systemic arterial hypertension involves abnormalities in blood pressure control. Orthostatic hypotension represents a failure of the
niormal peripheral vascular response to arising. A more specific defect in file control of
peripheral vaseulature occurs in Raynaud 's
disease. The regulatory mechanisms that influence erythropoiesis may produce anemia at
one extreme and polyeythemia at the other.
The eontrol of blood volume and of total body
fluids must be deranged when patients with
advanced cardiac disease develop peripheral
vaseular congestion and edema.
In addition to primary disturbances of control mechanisms, physicians must be alert to
changes in control systems iniduced by various
organic disease states. Consider a patient with
severe aortic insufficiency. In spite of voluminous uncontrollable regurgitation of blood
during each cardiac cycle, the net forward
flow of blood through the arterial system is
generally within the range of normal values
so lonig as the heart reinains compensated.
Similarly, the cardiac output tends to be
maintained even after large portions of the
ventricular myoeardiunn have been replaced
bv sear tissue after severe coronary occlusioni.
On the other hand, hyperthyroidism or emotionial states may impose sustained loads on
the hearts of patients that are unrelated to
disease of the cardiovascular system. From
this point of view it beconmes imnperative that
the basic control mechanisms of the cardiovascular system be as fully understood as possible.
Cardiac Control
If we conisider control of the heart in terms
of the definition and example proposed by Dr.
Peterson, many essential pieces of informiation
are missing. Since the heart is a pump, its
control must take the form of adjustments in
the heart rate or stroke voluine or both. If the
cardiac output is regulated by a sensing element that provides an error signal whenever
the cardiac output varies from some set value,
we eannot at present identifv the flow-sensing
nechanism; we do iiot know the mechanismn
by which the resting levels are "'set" nor can
we describe in any detail the afferent pathways or eoordinating ceniters for the appropriate reactions that maintain resting cardiac
output. It is tempting to assume that the normlal resting cardiac output represents the level
to which heart rate and stroke volume would
ten-d if all controls were removed. This con
cept does not appear applicable to the regulation of resting heart rate, which is the resultant of the mutually antagonistic effects of
svmpathetic and parasymupathetic nerves to
the pacemaker region. The parasympathetic
effects are generally regarded as dominant, so
that section of both sets of nierves leads to a
faster heart rate than the normal resting
value. Moreover, the cardiac index at rest
From the Department of Physiology and Biophysics, University of Washington School of Medicine,
Seattle, Wash.
Aided by a grant from the National Heart Institute, U. S. Public Health Service.
744
Circulation, Volume XXI, May 1960
SYMPOSIUM-CARDIOVASCULAR REGULATION
745
Pressure
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Figure 1
In a simple hydraulic system, the perfusion pressure can be maintained within narrow
limits by a servo-control system that produces appropriate changes tn pump output to
balance any net changes in peripheral resistance or vice versa. The correspondence between this basic pattern and the pressoreceptor mechanism is illustrated.
tends to be about the same for subjects with
either rapid or slow heart rates. In other
words, a relatively slow heart rate is associated
with a relatively large stroke volumne and vice
versa. If this is the case, the cardiac output
may be regarded as "set" in ternms of some
other criteria, i.e., peripheral tissue requireinents.
The flow of blood through peripheral tissues
might be regulated to maintain a constant environment for the various cells. Such regulation might involve chemoreceptors in the systemic veins to monitor oxygen content of venous blood to provide sensing elements for
proper adjustment of peripheral flow distribution and cardiac output. Such adjustments
would be truly applicable onlv to those tissues
in which blood flow is dependen-t upon metaCirculation, Volume XXI, May 1960
bolic rate and oxygen consumption, i.e., skeletal
muscle. No chemoreceptors have been demonstrated in the various systemic veins thus far.
Since skin serves an essential function in heat
exchange, proper sensing elements to "set"
blood flow through the subeutaneous tissues
would be some form of temperature receptors.
What would be the most appropriate sensory
elements to monitor renal blood flow, gastrointestinal perfusion or circulation through
olands ? We have not found such receptors as
might be required for these purposes. Indeed,
in many instances we would not even know
what to look for.
The traditional view of cardiac output regulation revolves about a mechanism for maintaining systemic arterial pressure to provide
an effective balance between peripheral blood
746
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flowv aiicl cardiac output. The basie prinieiples
of this regulation are illustrated in figure 1.
If thc perfuLsion pressure is ii-iain-taiined constant by meatis of servo-conitrol, anly net
changae iii periphleral flowv is promiaptly countered by the appropriate increlase iui cardiac
output. The distortioni receptors in the carotid
sirius and aortic arch could seirve as appropriate senisor-y elemnenits to imioniitor systemic
arterial I)rcssure. Theoretically, chlanges in the
discharge frequeney along the nerves fromn
the pressoreeptors influence medullary etardioregulator cen-iters, so that aniy reduction inh
arterial pressure would be pr omptly countered by the proper degrlee of taelhyeardia and
compenisatory vasoeoinstriction in inactive tissues to maintain systemic arterial pressure
within a narrow rane.relihe pressoreceptor
mechanism lhas received a great deal of attention, siniee it is the onily neural feed-back loop
for cardiovascular conitrol that has beenl deselibed in som-e detail. AW'henever this mecli
aniism p)1ays a doinitiant regulatory role, tachycardia should be associatcd with any reductioni
in eani systenmie arterial pressure. Elevated
sy.stemic arterial pressure slhould be aecompaniied by bradyeardlia. Oln tlhe contrary, car(liovascular responises of initact dogs during,
sponltanleous activity frequiently display tachyeardia dluringc elevation of systolic ventricular
pressur e (fig. 2). Othier studies have indicated
that these coniditionis ar-e also freequently clharaeterized by inicreased meicani arterial pressure.
Apparenitly the sympathetic diseharge to the
Circulation, Volume XXI, May 1960
SYMPOSIUM-CARDIOVASCUIAR REGULATION
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heart under these conditions overrides the
pressoreceptor mechanism. Under these con(litions, the arterial pressure controls cannot be
regulating cardiac output. Dr. Peterson will
present additional information regarding this
important mechanism.
According to traditional coneepts, a mechanism for adapting the stroke volume to the
circulatory requirements was embodied in the
length-tension relationships of the myocardium, and no external control need be postulated. This mechanism is clearly dominant in
isolated or exposed hearts under experimental
conditions. Similarly, iniereased stroke volume
and stroke work accomnpany increased diastolic
distention in intact animals during the transition from the standing to the recumbent position.1 2 However, other forms of cardiovascular adjustments appear to be initiated primarily by increased discharge of sympathetic
nerves to the heart and peripheral vasculature.
In a dog that is familiar with treadmill exercise, confronting him with the switch that
turns on the motor-driven treadmill will characteristically induce changes in left ventrieular performance that simulate those produced
by the running at 3 m.p.h. on a 5 per cenit
grade (fig. 2C). The left ventricular response
to this treadmill exercise generally involves a
prompt elevation in left ventricular systolic
pressure accompanied by an equally abrupt
tachyeardia.3 4 In the particular example presented in figure 2, the systolic ventricular
pressure was elevated when the treadinill
switch was presented but not during the exertion. Thus an inappropriate stimulus produced a more typical response in figure 2C
than did the appropriate stimulus in figure
2D and 2E. The left ventricular response to
treadmill exercise at 3 ni.p.h. on a 5 per cent
grade can also be quite precisely duplicated
by electrical stimulation in 2 discretely localized sites in the diencephalon (in the H2 field
of Forel and the periventricular gray matter).
The response can be elicited by very weak
stimulation without movement by the animals
with or without anesthesia.3 4
The initiation of changes in circulatory patCirculatiorn, Volume
XXI, May 1960
747
tern by increased discharge from the higher
levels of the nervous system does not necessarily constitute a regulatory mechanism under the definition presented by Dr. Peterson,
since no sensing mechanisms, setting mechanisms, or feed-back loops have been implicated.
(This is analogous to the occupant of the
house resetting the thermostat.) Adjustments
in the cardiovascular system initiated voluntarily or from higher levels of the nervous system might more appropriately be regarded as
control rather than regulation. When a dog
exercises for the first time on the treadmill,
virtually all the recorded parameters tend to
display an overshoot for 10 or 15 seconds and
then settle down to a fairly constant level.
However, by the third or fourth bout of exercise, this teiidency to overshoot largely or completely disappears. This looks like modulation
of an excessive cardiovascular response by unknown regulatorv mechanisms.
Summary
If a regulating system consists of a mechanism for sensing the essential parameters,
detecting deviations from a "set" value, and
initiating corrective action, then the arterial
pressure-regulating mechanism is the only
regulating system described for the cireulation
in any detail. This mechanism appears to be
important in maintaining a level of mean arterial pressure within a narrow range. It does
not appear, however, to play a dominant role
in adjusting the level of the circulation to
meet spontaneously changing circulatory demands under many circumstances. During
spontaneous activity by intact dogs, an increase in systolic ventricular pressure (and
mean arterial pressure) is frequently accompanied by tachyeardia as though some other
mechanism were overriding the pressoreceptor
mechanism. Thus, it appears that the circulatory system as a whole is largely controlled by
neural meehanisms, usually initiated by
higher levels of the nervous system. Very little
is known of the sensory limbs of reflex arcs
that can serve to regulate the cardiovascular
system as a whole.
748
RUSHMER
Summario in Interlingua
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Si uil systeina regulatori pote esser definiite coino
all mechanismo que percipe le parametros essential
del processo a regular, que detege deviatioiues ab certe
valores establite pro ille paramientros, e que iiiitia
actiones corrective quando tales es indicate, alora le
iieclhanismo del regulation de tension es le sol systeiiia regulatori in le complexo del eirculatioat que lha
essite describite in detalio. Iste ieelhaiisnio pare
esser iiiportanite pro mantener le niivello nmedie del
tenision arterial intra strictissime limites. Tamnen, illo
non pare haber un rolo dominante in adjustar le nivello
del circulation in responsa a spontaneemente alterate
requirimentos eirculatori sub varie circumstantias.
Durante spontanee activitates per canies intacte, un
augmento del tension ventricular systolic (e del tensioil arterial medie) es frequentemente accompaniate
de tachyeardia, de maniera que on ha le impression
que un altere mechanismo se iinponie eoin vigor supe-
Iiior super le mnechanismo pressoreceptori. Assi il pare
que le systema eirculatori in su totalitate es regulate
in grande mesura per mechaiiismos neural que es
usualmente initiate per nivellos plus alte del systema
nervose. Pauchissimo es eognoscite del circuitos sensoni O (tel arcos retlexe que pote servir a regular le
systeiia cardiovascular in su totalitate.
References
1. RUSHMER, R. F.: Postural effects oni the baselines of ventricular performance. Circulation
20: 897, 1959.
2. SJOSTRAND, T.: Regulatory mechanisimis relating
to blood volume. Minnesota Med. 37: 10, 1954.
3. RuSHMER, R. F., AND SMIITH, 0. A.: Cardiac
Control. Physiol. Rev. 39: 41, 1959.
4. -, -, AND FRANKLIN, D.: Mechanisms of
cardiac control in exercise. Ciriculation Research 7: 602, 1959.
Circulation, Volume XXI, May 1960
Regulation of the Heart's Functions
ROBERT F. RUSHMER
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Circulation. 1960;21:744-748
doi: 10.1161/01.CIR.21.5.744
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1960 American Heart Association, Inc. All rights reserved.
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