Download Pulmonary resistance in cardiovascular context

International Journal of Cardiology 97 (2004) 3 – 6
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Pulmonary resistance in cardiovascular context
Philip J. Kilner
Cardiovascular Magnetic Resonance Unit, Royal Brompton and Harefield NHS Trust, Sydney Street, London SW3 6NP, United Kingdom
Available online 22 September 2004
Abstract
Comparison of the human cardiovascular system with arrangements of circulatory systems found in lower vertebrates and invertebrates
allows appreciation of the functional elegance of our double circulation with systemic and pulmonary vascular trees served by a single looped
and septated heart. In the pulmonary part of the circulation, consideration of the nature of alveolar microvessels in relation to the system as a
whole may throw light on the pathophysiology of pulmonary regurgitation and pulmonary hypertension. Pulmonary microvessels impose
remarkably little resistance to flow compared with the systemic. This may be attributed to their delicate, compliant structure, with tissue
support on one side only, their respiratory walls remaining relatively free to expand in alveolar air. Low resistance may also depend on the
branch pattern of alveolar capillaries, with almost immediate proximity between bifurcations and confluences in a uniquely dense,
interconnected network. In the presence of free pulmonary regurgitation, pulmonary microvessels probably play a valve-like role,
representing a low-resistance boundary or watershed between pulmonary arteries and veins. This microvascular watershed imposes little
resistance to systolic forward flow, but in diastole, with venous pressures being kept low by function of the left heart, there is presumably
little or no reversal of gradient to move blood back through the capillaries. The delicacy and potential vulnerability of alveolar capillaries to
elevation of flow and pressure is likely, however, to go with a protective feedback circuit which, in abnormal circumstances, could contribute
to development of arteriolar medial hypertrophy and pulmonary arterial hypertension.
D 2004 Elsevier Ireland Ltd. All rights reserved.
Keywords: Cardiovascular morphology; Pulmonary hypertension; Pulmonary regurgitation
1. Overall cardiovascular arrangements
Among various phyla and classes of the animal kingdom,
the higher vertebrates, including humans, have a unique
arrangement of the heart and circulatory system, with systemic and pulmonary vascular trees supplied by separate but
adjacent left and right sides of a single heart [1,2]. This is of
course well known and perhaps taken for granted, but comparison with alternative cardiovascular arrangements found
among the invertebrates gives perspective for appreciation
of the functional significance of the layout of our own
system.
No organ that can be called a dlungT occurs among
animals other than the air-breathing vertebrates. In contrast,
insects have multiple small tracheal tubes that convey air
directly into metabolising tissues of the body, but no lungs.
Among living invertebrates, aquatic cephalopod molluscs
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doi:10.1016/j.ijcard.2004.08.002
(octopus and squid) attain the largest sizes and probably the
greatest degree of organic complexity. They have rudimentary sub-respiratory dheartT cavities known as gill hearts,
upstream of the vessels perfusing the gills. The gill hearts
develop from bilateral vessel segments separate from the
systemic heart and not by septation of the main heart tube
into left and right sides. Snails that have taken to the land
which are also molluscs, have incorporated an air-space
adjacent to a modified gill structure known as the
cnetidium, located under the front part of the shell. These
snails have a heart structure remarkably similar in plan to
the basic vertebrate heart found in fish, namely a single
atrium and single ventricle, with inflow and outflow valves,
contained by a pericardium. But in spite of its similarity of
plan, this dorsal heart seems to have evolved quite
separately from its ventral counterpart in the fish. Unlike
the vertebrate heart, the snail heart shows no looping. Its
output is to systemic followed by respiratory vessels, which
is the reverse of the order found in fish.
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P.J. Kilner / International Journal of Cardiology 97 (2004) 3–6
2. Vertebrate heart forms
Vertebrates include fish, amphibia, reptiles, birds and
mammals. All of these have their main, systemic heart
located ventrally in the organism. Other valved and
contractile vessel segments may exist, for example, the
caudal and hepatic hearts of hagfish and lymphatic dheartsT
of amphibia, but there is always one principal systemic
heart, surrounded by pericardium, and located ventrally in
the thorax that generates most of the pressure and flow for
the circulatory system. In fish, blood from the ventricle
perfuses microvessels of the gills before passing on to those
of the systemic organs and muscles. This sequence, which
contrasts with that found in the molluscs, does not seem
ideal for maintenance of low pressure in respiratory microvessels, especially during exercise. This potential problem
may have given impetus for evolution of an alternative
arrangement in higher vertebrates. Separation of pulmonary
from systemic circulations by gradual septation of the heart
coincides with the emergence of vertebrates from water to
land and with the development of lungs. The hearts of
higher, air-breathing vertebrates—reptiles, birds and mammals—combine three characteristic features that are not
found among invertebrates:
Firstly, there is progressive looping, which may be defined
as sinuous direction changes of flow, at atrial, ventricular and
at great arterial level. Looping of the heart is not only retained
from lower to higher vertebrate classes, but becomes increasingly marked, with acute changes of direction through the
hearts of reptiles, birds and mammals. Arguably the
asymmetries and direction changes of flow associated with
looped curvature facilitate efficient, sling-like heart action as
velocities and rates of change of momentum increase with
exertion [3,4].
Secondly, there is gradual septation and separation of
right from left atrial, and right from left ventricular cavities.
While atrial septation is complete in amphibians, reptiles,
birds and mammals, ventricular septation remains partial in
amphibians and most reptiles, becoming complete in birds
and mammals. Complete atrio-ventricular septation allows
effective separation of low-pressure pulmonary from highpressure systemic arterial flows, which remain in continuity
with one another in the whole circuit via the peripheral
microvascular connections.
The third morphological feature, which goes with
ventricular septation, is spiral septation of the outflow tracts.
The outflow tracts of right and left ventricles curve helically
around one another. The functional importance of spiral
division is apparent from the consequences of its absence in
congenital heart disease. In transposition of the great arteries
(ventriculo-arterial discordance), the left and right ventricular outflow tracts run parallel to one another, the outflows
apparently having been divided by dstraightT rather spiral
septation. This implies that, given concordant atrio-ventricular connections, spiral septation of outflows has evolved to
achieve appropriate delivery of deoxygenated (systemic
venous) blood to pulmonary arteries, and oxygenated
(pulmonary venous) blood to systemic arteries.
Fig. 1. Drawing, based on magnetic resonance flow studies, of principal paths of flow through left and right sides of the human heart in diastole (left) and systole
(right). It shows relations of the two sides of the one heart, with direction changes of flow at atrial, ventricular and arterial levels, and spiral division of outflow
tracts.
P.J. Kilner / International Journal of Cardiology 97 (2004) 3–6
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So all three features of heart form—looping, septation
and helical division of outflows—are functionally significant. The looped and helically septated heart of higher
vertebrates appears to be an elegant design for simultaneous
and efficient function of low-pressure pulmonary and highpressure systemic circulatory systems over a range of
physiological conditions from rest to strenuous exercise
(Fig. 1).
3. Pulmonary and systemic microvascular resistance
The diameters of capillary microvessels throughout the
body are less than 10 Am, which is about 1/10 of a hair’s
breadth. Blood cells pass in single file and have to deform
through these delicate, microscopically small vessels, where
they are brought into proximity with air of the alveoli and
metabolising cells throughout the body. It is remarkable that
the whole cardiac output, about 5 l/min in an adult, can pass
through such minute vessels.
It is also remarkable that output of the right heart to the
lungs alone requires only about one fifth of the arterial
pressure required to propel the same output through
microvessels of the whole of the rest of the body. This
means that total pulmonary resistance is only about one
fifth of total systemic resistance. As the total volume of
the lungs (about 6 l) is so much less than that of the rest
of the body (about 65 l), pulmonary vascular resistance
per unit volume of lung is less than one fiftieth of
systemic vascular resistance per unit volume of tissue. The
difference per unit weight of tissue would be even more
extreme.
The overall perfusion of body and lungs depends, of
course, on there being many billions of capillaries, all linked
to and from the heart by the branches of arterial and venous
trees. The numbers of capillary branches are such that, in
spite of their microscopically small diameters, the cumulated cross-sectional areas of capillaries summate to many
times the cross-sectional area of the great vessels, which is
reflected in marked deceleration of flow during passage
from large central to small peripheral vessels via the
repeated branching of arteries [5]. Blood seeps rather than
flows through intricate capillary webs.
The low-resistance capillary beds of the alveoli of the
lungs have a unique pattern of branching and reconnection.
Alveolar capillaries are distributed in a densely interconnected net with extremely short distances between branches
and confluences (Fig. 2). Alveolar blood seeps through
these capillary nets almost as a sheet or film, split only by
the columns of epithelium that form the holes of the net [6].
These networks of alveolar microvessels must be particularly delicate and compliant, being supported by tissue on
one side only, the other side being exposed alveolar air. This
is necessary for respiratory gas exchange, but it may also
imply extra vulnerability to any elevation of intra-capillary
pressure.
Fig. 2. Scanning electron micrograph showing human alveolar capillaries
from a child who had been born with a ventricular septal defect. The
interconnected web of capillaries, when filled as here, bulges into the air
spaces of the alveoli. In contrast, systemic capillaries are generally
embedded in surrounding tissues and have greater lengths between
junctions. Scale bar = 20 Am (from reference [6]).
On the systemic side, the spatial arrangements of
microvessels vary considerably between organs, but the
systemic capillaries, unlike those of the alveoli, are
predominantly linearly arrayed, with many diameter-lengths
between points of branching or confluence. While muscular
arterioles with pre-capillary sphincters are known to modify
local perfusion, the lengths and branch patterns of systemic
capillaries, as well as their diameters, must contribute to the
resistance, or lack of resistance, to microvascular flow.
4. Pulmonary regurgitation
Free pulmonary regurgitation, as found after repair of
Tetralogy of Fallot or in absent pulmonary valve syndrome,
is generally well-tolerated for decades. Interestingly, free
pulmonary regurgitation is typically associated with a
regurgitant fraction of only about 40% [7]. This contrasts
with aortic regurgitation. Free aortic regurgitation is not
compatible with life, and an increasing aortic regurgitant
orifice can be associated with as much as 60% regurgitant
fraction, beyond which cardiac and circulatory failure are
likely to follow. How can free pulmonary regurgitation be so
relatively well tolerated?
Part of the answer lies in the secondary role of the right
heart with respect to the left. It is possible for left heart
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P.J. Kilner / International Journal of Cardiology 97 (2004) 3–6
function alone to support both the systemic and pulmonary
flows in series, as illustrated by the Fontan circulation. To
some degree, this happens in the presence of free pulmonary
regurgitation where, with a so-called drestrictiveT right
ventricle, rising systemic venous and right heart pressures
during diastole result in forward flow in the pulmonary
artery at the time of atrial systole [8]. This occurrence will
boost the proportion of forward pulmonary flow relative to
regurgitant flow. However, there is probably another factor
that limits the severity of free pulmonary regurgitation. This
is valve-like function of the pulmonary microvessels. Right
ventricular systole results in forward flow in the pulmonary
arteries, a proportion of which must pass forward through
the low-resistance microvessels to pulmonary veins. This
blood is unlikely to return in diastole, having descapedT to a
lower-pressure region, maintained by function of the left
heart. The delicate, compliant pulmonary capillaries represent a low-resistance boundary or watershed between
pulmonary arteries and veins, not too far removed in
distance from the right ventricle. So the combination of
Fontan-like function of the circulation as a whole and a
valve-like function of pulmonary microvessels in this
context may combine to limit the adverse impact of free
pulmonary regurgitation.
5. Pulmonary hypertension
A characteristic histological feature of pulmonary hypertension, whether primary or secondary, is thickening and
proliferation of medial smooth muscle of pulmonary arteries
and arterioles [9–11]. There is also thickening of the interna,
eventually leading to obliteration of the lumen and development of plexiform vascular lesions. Various biochemical
pathways are being investigated in the search for understanding of the pathogenesis of pulmonary hypertension. It
could be that there is a physiological feedback mechanism
built in to protect the delicate capillary nets of the alveoli
from excessive flow and pressure through the range of
physiological states from rest to exercise. This protective
mechanism is likely to include activation of arteriolar
smooth muscle. So it may be an exaggeration of a
physiological response that underlies the changes seen in
pulmonary hypertension, particularly when it is secondary
to shunting and excessive pulmonary flow.
6. Summary
The double systemic-pulmonary circulation, served by a
looped and spirally septated heart, is unique to humans and
other higher vertebrates. My aim has been to consider
pulmonary resistance in the context of the cardiovascular
system as a whole. In this context, the delicacy, compliance
and location of pulmonary microvessels give them a
potentially beneficial, valve-like role when there is free
pulmonary regurgitation, although it leaves them vulnerable
to elevation of flow and pressure. Natural protective
feedback mechanisms may, in slightly altered forms,
underlie the pulmonary arterial and arteriolar changes
characteristic of pulmonary hypertension.
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