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SEPTEMBER
VOL. II
Circulation Research
1954
NO. 5
A Journal of the American Heart Association
Editorial
Cardiovascular Reactivity
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formation, cannot be applied indiscriminately
to the total circulation. Measurement of
arterial pressure, or cardiac output, has the
advantages of easy measurability and reproducibility, but the mechanisms of blood pressure and flow regulation are multiple and
complex; cardiac output and total peripheral
resistance need to be considered in each case.
Analysis of central arterial pulse contours
yields simultaneous indices of both output
and resistance, as well as useful information
regarding state of myocardial integrity, but
the method requires considerable skill and
training in its use and is not applicable to
many experimental preparations. As an
alternative, arterial pressure provides as
practical and convenient a measurement of
cardiovascular reactivity as is currently available. When a change in reactivity is of demonstrable interest, then information obtained
from pressure measurements can be supplemented by that obtained by measuring cardiac
output and flow and resistance through different specialized vascular beds. As an example,
serotonin injected intravenously was found to
be pressor or depressor depending upon
whether vasomotor outflow was respectively
absent or increased. Measurement of reactivity
in selected portions of the vascular bed then
demonstrated that serotonin was directly
vasodilator or vasoconstrictor depending upon
degree of vasomotor outflow. Other methods
of measuring reactivity, both of the heart and
peripheral vascular system, will further clarify
the nature of action of this drug and the
mechanisms regulating reactivity to it. As
another example, change in reactivity after
T
HE great variation in cardiovascular
response to standard stimuli from
animal to animal, and from man to
man, is gradually being recognized as a major
problem of the medical sciences. Those conditioning, or regulating, mechanisms that
determine degree of responsiveness, and account for variation in response, are at least
as important as the stimulus. It is all too
common for physiologists and pharmacologists
to think in terms of the amount of stimulation
required to elicit a specific response, and to
consider that a given amount of drug will
elicit a "standard" response. Were this the
case, study of the cardiovascular system would
at once be enormously simplified; instead,
reactivity is highly variable, not only from
animal to animal, but in the same animal from
time to time, and degree of reactivity is often
the primary determinant of the response.
Cardiovascular reactivity may be denned as
the degree with which the heart and peripheral
vascular bed respond to quantitated stimuli,
whether the latter be drugs, reflex nervous
activation, or nerve stimulation. Total response
does, of course, represent an algebraic summation of responses and counter-responses,
and separation of this total response into its
component parts is, at best, difficult. Reactivity in isolated organs, the heart, or discrete
portions of the vascular bed may be measured
separately, and this measurement has the
advantage of homogeneity, but has the disadvantage of representing relatively small and
specialized parts of the vascular tree. These
measurements, while yielding valuable in395
Circulation Research, Vol. II, September 1954
396
EDITORIAL
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denervation has been profitably investigated
in the same manner.
Cardiovascular response to noradrenaline
released from nerve endings must depend
upon (I) reactivity, which is determined by a
wide variety of mechanisms, and (2) amount
of noradrenaline released. Normally, there
would seem to be a nice balance between these
two determinants so that arterial pressure is
maintained at reasonably constant levels. But
since reactivity to injected noradrenaline is
often observed to change markedly over
short periods of time, without change in
mean arterial pressure, it would also seem that
these two factors act oppositely and in varying
proportions. Thus, mechanisms controlling
reactivity may participate in the maintenance
of normal blood pressure as importantly as
the carotid sinus and aortic buffer reflexes.
Factors Influencing Cardiovascular Heart iuitt/
A. Nervous
1) sympathetic denervation or decentralization
2) sympathetic stimulation
3) alteration in activity carotid sinus and aortic
buffer mechanisms
•I) action of drugs on a) central nervous system
b) sympathetic ganglia
c) myoneural junction
B. Humoral
1) diverse actions of substances of hepatic,
renal, adrenal, neural, thyroidal and pituitary-hypothalamic origin
C. Chemical environment of vascular muscle and
nervous tissue
1) electrolyte composition, oxygen
tension,
anesthetic agent
2) hormonal
D . Physical environment of vascular muscle
1) stretch, temperature, hydration
10. Intrinsic qualities of vascular muscle
1) species and organ specificity
V. Systems regulating the humoral environment of
muscle and nervous tissue
1) enzymatic synthesis and destruction, conjugation
2) excretion, storage and rate of libeiation
Some of the mechanisms influencing reactivity have been determined. Undoubtedly
there are many others. Accurate measurement
of their degree of participation in normal
physiology and in disease has but begun. But
there seems to be ample evidence that they do
participate, and they must surely work in
harmony through steady-state equilibria. Some
of the regulatory mechanisms and procedures
that do influence cardiovascular reactivity are
classified broadly in the accompanying table.
It is tempting to postulate that change in
reactivity alone may be responsible for altered
cardiovascular function. The prehypertensive
state, for instance, which is characterized by
increased response to emotional stimuli and
cold, might be due to change in reactivity to
normal reflex vasomotoi discharge. Some evidence suggests that this is the case. It seems
logical to assume that normal vasomotor
outflow should result in hypertension if reactivity to noradrenaline was greatly increased,
just as hypertension should result from relatively small amounts of renal or other pressor
agents if sensitivity to them was increased.
And it seems improbable that hypertension
could develop in any patient, at least to a
severe degree, if reactivity to the responsible
pressor agent was greatly diminished.
The development of irreversible shock may
depend upon an opposite change in reactivity.
Early after hemorrhage, arterial pressure is
maintained to a large extent by compensatory
vasomotor reflexes. Later, sensitivity to angiotonin, and then noradrenaline, diminishes and
this loss is associated with further decline in
blood pressure. When reactivity is so
diminished, replacement of blood is not usually
restorative. Thus, at these two extremes of
cardiovascular dysfunction, hypertension and
shock, reactivity may be an important participating mechanism.
IKVIXK II. PAGE
J. W. MeOcBBix
Cardiovascular Reactivity
IRVINE H. PAGE and J. W. McCUBBIN
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Circ Res. 1954;2:395-396
doi: 10.1161/01.RES.2.5.395
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Copyright © 1954 American Heart Association, Inc. All rights reserved.
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