Partial aortic occlusion and cerebral venous steal: venous effects of arterial manipulation in acute stroke.

Abstract

Acute ischemic stroke therapy emphasizes early arterial clot lysis or removal. Partial aortic occlusion has recently emerged as an alternative hemodynamic approach to augment cerebral perfusion in acute ischemic stroke. The exact mechanism of cerebral flow augmentation with partial aortic occlusion remains unclear and may involve more than simple diversion of arterial blood flow from the lower body to cerebral collateral circulation. The cerebral venous steal hypothesis suggests that even a small increase in tissue pressure in the ischemic area will divert blood flow to surrounding regions with lesser tissue pressures. This may cause no-reflow (absence of flow after restoration of arterial patency) in the ischemic core and "luxury perfusion" in the surrounding regions. Such maldistribution may be reversed with increased venous pressure titrated to avoid changes in intracranial pressure. We propose that partial aortic occlusion enhances perfusion in the brain by offsetting cerebral venous steal. Partial aortic occlusion redistributes blood volume into the upper part of the body, manifested by an increase in central venous pressure. Increased venous pressure recruits the collapsed vascular network and, by eliminating cerebral venous steal, corrects perifocal perfusion maldistribution analogous to positive end-expiratory pressure recruitment of collapsed airways to decrease ventilation/perfusion mismatch in the lungs.

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ISSN: 1524-4628
Copyright © 2011 American Heart Association. All rights reserved. Print ISSN: 0039-2499. Online
Stroke is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514
DOI: 10.1161/STROKEAHA.110.603852
published online Mar 24, 2011;
Stroke
Osvaldas Pranevicius, Mindaugas Pranevicius and David S. Liebeskind

Manipulation in Acute Stroke
Partial Aortic Occlusion and Cerebral Venous Steal: Venous Effects of Arterial
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Partial Aortic Occlusion and Cerebral Venous Steal
Venous Effects of Arterial Manipulation in Acute Stroke
Osvaldas Pranevicius, MD, PhD; Mindaugas Pranevicius, MD; David S. Liebeskind, MD
Abstract—Acute ischemic stroke therapy emphasizes early arterial clot lysis or removal. Partial aortic occlusion has
recently emerged as an alternative hemodynamic approach to augment cerebral perfusion in acute ischemic stroke. The
exact mechanism of cerebral flow augmentation with partial aortic occlusion remains unclear and may involve more than
simple diversion of arterial blood flow from the lower body to cerebral collateral circulation. The cerebral venous steal
hypothesis suggests that even a small increase in tissue pressure in the ischemic area will divert blood flow to
surrounding regions with lesser tissue pressures. This may cause no-reflow (absence of flow after restoration of arterial
patency) in the ischemic core and “luxury perfusion” in the surrounding regions. Such maldistribution may be reversed
with increased venous pressure titrated to avoid changes in intracranial pressure. We propose that partial aortic occlusion
enhances perfusion in the brain by offsetting cerebral venous steal. Partial aortic occlusion redistributes blood volume
into the upper part of the body, manifested by an increase in central venous pressure. Increased venous pressure recruits
the collapsed vascular network and, by eliminating cerebral venous steal, corrects perifocal perfusion maldistribution
analogous to positive end-expiratory pressure recruitment of collapsed airways to decrease ventilation/perfusion
mismatch in the lungs. (Stroke. 2011;42:00-00.)
Key Words: aortic occlusion ? collateral ? hemodynamics ? ischemia ? stroke ? venous
A
stroke therapy using a form of partial aortic occlusion.1
However, to develop more targeted stroke treatment methods,
we must understand the mechanism through which an acute
cardiac afterload augmentation improves CBF. Currently, the
effect of partial aortic occlusion is attributed to redistribution
of cardiac output from the lower body to the brain. We
present an alternative hypothesis that another overlooked
effect of acute cardiac afterload augmentation through aortic
manipulation is an increase in cardiac preload and propose
that this increase might be the primary cause of the observed
CBF augmentation. The simple diversion of arterial blood
flow from the lower torso and extremities to the leptomenin-
geal arterial collaterals is unlikely and flow augmentation in
the collaterals may be dependent on a venous mechanism.2
n observation that aortic manipulation can augment
cerebral blood flow (CBF) was directly translated to
Effects of Partial Aortic Occlusion
Hemodynamics in any circulation must consider all segments
of the vascular bed, from arterial to venous. Similarly, cardiac
output is not a fixed variable, but rather depends on the
preload, afterload, and cardiac contractility. Blood flow
diversion to the upper torso can occur, but only in the case of
fixed cardiac output, as with severe aortic stenosis or in the
case of an open circulatory system, such as severe hemor-
rhage. Partial aortic occlusion is the physiological equivalent
to an abrupt increase in afterload. A sudden increase in
afterload has 2 immediate effects—decrease of cardiac out-
put and increase in arterial pressure.3Increase in arterial
pressure might be beneficial in some settings, such as
systemic hypotension or when CBF depends predominantly
on pressure.4Blood pressure augmentation or induced hyper-
tension may have limited utility for CBF enhancement after
stroke in normotensive patients.5If the hemodynamic effects
of partial aortic occlusion after stroke extend beyond blood
pressure augmentation, then alternative CBF modulation
mechanisms must be implicated.
Cerebral Venous Steal in Stroke
Cerebral venous steal or diversion of blood flow to the
periphery of the ischemic territory follows focal venous
compression.6Regional blood flow ceases when the focal
tissue pressure (Pe) approaches inflow pressure (Pi). Pressure
decreases across the circulatory pathway; highest pressures
are exhibited in the arteries and progressively diminish
toward the capillary segments. During stroke, an obstruction
of the inflow artery decreases pressure to a greater degree,
and often pressure is sustained only via the collateral circu-
lation.7Because of this pressure decrease in the arteries, the
inflow pressure at capillary level becomes an even smaller
Received October 14, 2010; accepted January 25, 2011.
From the Department of Anesthesiology (O.P.), New York Hospital Queens, Flushing, NY; Department of Anesthesiology (M.P.), Albert Einstein
College of Medicine, Jacobi Medical Center, Bronx, NY; UCLA Stroke Center (D.S.L.), University of California, Los Angeles, CA.
Natan M. Bornstein, MD, was the consulting editor for this paper.
Correspondence to Osvaldas Pranevicius, MD, PhD, 300 Albany St-6E, New York, NY 10280. E-mail opranevicius@aol.com
© 2011 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.orgDOI: 10.1161/STROKEAHA.110.603852
1
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fraction of the arterial pressure. Therefore, even slight focal
tissue pressure increases could significantly reduce capillary
perfusion, especially in the presence of a diversion pathway,
which has lower effective outflow pressure. Diverted blood
flow creates steal in the center and luxury perfusion at the
periphery. Increased venous pressure equalizes the effective
outflow pressures and diminishes this maldistribution. Con-
versely, an increase in venous pressure (Pv), as long as it
remains below the tissue pressure Pe, does not impede focal
penumbral blood flow, but rather enhances it by reversing the
cerebral venous steal.
Optimal Venous Pressure
According to the parallel Starling resistor model, penumbral
flow is maximized when venous pressure approaches tissue
pressure; any venous pressure increase beyond the tissue
pressure will decrease cerebral perfusion pressure. The only
question remaining is what is the local penumbral tissue
pressure? Local penumbral tissue pressure Pe is virtually
impossible to measure in the clinical setting, but it can never
be lower than intracranial pressure if brain edema is present.
Hence, intracranial pressure can be used as a marker of the
level to which venous pressure can be safely increased
without the fear of decreasing global cerebral perfusion
pressure; critical closing pressure, which can be estimated
noninvasively, also can be used as an alternative surrogate
measure. As venous pressure reaches the level of critical
closing pressure or intracranial pressure, it causes their in-
crease; however, as long as it stays below the level of critical
closing pressure or intracranial pressure, it has no effect on these
variables.8Alternatively, an optimization of venous pressure
after stroke can be performed in the same way cardiac preload is
optimized with respect to the cardiac output: an incremental
venouspressureincrease/decreaseuntilthetargetperifocalblood
flow reaches peak.
Aortic Occlusion Redistributes Blood Volume to the
Upper Body
Redistribution of the systemic blood volume from the
splanchnic circulation is a well-known effect of partial aortic
occlusion. Although most of what we know about redistribu-
tion of blood volume after aortic occlusion comes from
animal studies, this knowledge is used widely to manage
patients undergoing surgery requiring aortic cross-clamping.
The splanchnic organs contain nearly 25% of the total blood
volume stored in the venous vasculature. After aortic occlu-
sion, nearly two-thirds of this volume (?800 mL) is auto-
transfused into the systemic circulation within seconds,8,9
causing an instantaneous increase in central venous pressure.
In a previous study, aortic cross-clamping in dogs resulted in
marked increases in mean arterial pressure by 84% and
end-diastolic left ventricular pressure by 188%, whereas
simultaneous cross-clamping of the aorta and inferior vena
cava resulted in no significant change in preload or in mean
arterial pressure.10Cardiac stroke volume was reduced by
74%.10Interestingly, by transfusing blood during clamping of
the inferior vena cava, the investigators re-established the
hemodynamic effect of thoracic aortic cross-clamping alone.
This study also demonstrated that thoracic aortic cross-
clamping, similar to partial aortic occlusion adjacent to the
renal arteries, is associated with a dramatic increase (155%)
in blood flow above the clamp level, whereas no such change
occurred with simultaneous aortic and inferior vena cava
occlusion. Another study demonstrated that aortic cross-
clamping at the diaphragmatic level was associated with
significant increases (by 8%–38%) in the ?-emission in all
organs and tissues above the level of aortic occlusion. These
studies support the hypothesis that cross-clamping of the
aorta at the diaphragmatic level is associated with an increase
in blood volume, not necessarily blood flow, in the organs
and tissues proximal to the level of cross-clamping.11
The effects of aortic cross-clamping also have been as-
sessed with respect to intracranial hemodynamics. Cerebral
blood volume was assessed in 8 pigs undergoing cross-
clamping of the descending thoracic aorta for 30 minutes
using MRI before cross-clamping, during cross-clamping,
and after declamping.12Ventricular volume decreased after
cross-clamping of the descending thoracic aorta. Because no
cerebral edema was observed, the decrease of ventricular
volume could only be attributed to increased intracranial
blood volume and an increase in venous outflow pressure.12
Clamping of the thoracic aorta alone (n?10) was accompa-
nied by severe arterial hypertension, a dramatic decrease in
inferior vena cava flow, and a dramatic increase in superior vena
cava flow. Simultaneous clamping of the thoracic aorta and
inferior vena cava (n?13) was accompanied by no significant
change in arterial pressure or superior vena cava flow.13
Yet, how may increased blood volume in the upper part of
the body exert a potential beneficial hemodynamic effect in
stroke? It is important to consider that an increase in blood
volume is inevitably associated with venous pressure eleva-
tion. Such venous pressure elevation may equalize effective
outflow pressure throughout the brain and abolish a steal-like
phenomenon, previously termed “cerebral venous steal.”6
Even limited ischemic tissue injury after arterial occlusion
may cause intraparenchymal pressure gradients.14These pres-
sure gradients are transmitted from parenchyma to the cere-
bral vasculature, determining effective outflow pressure if it
is higher than venous pressure (West zone II). Figure 1
illustrates how venous pressure affects regional CBF in
regions with normal tissue pressure (Pe?0, Ohms resistor);
homogeneously increased tissue pressure (Pe?constant ?0,
Starling resistor) and heterogeneously increased tissue pres-
sure (Pe variable, ?0, venous steal prone anatomy). Equal-
izing venous and focal tissue pressures equilibrates effective
outflow pressure in the perifocal area. When this occurs,
cerebral venous steal is abolished, heterogeneity in the
cerebral tissue perfusion is reduced, and blood flow is
restored to the areas of increased tissue pressure, possibly
translating into improved clinical outcomes.15An idealized
Starling resistor model predicts that blood flow can be
re-established from zero to ?50% of normal simply by
increasing venous pressure (Figure 2). One of the simplest
means of restoring flow without decreasing cerebral perfu-
sion pressure is head-down tilt, whereas head-up tilt may
decrease cerebral perfusion pressure because of cervical
venous collapse.16
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Pharmacological Alternatives to Partial Aortic Occlusion
Moderate venous pressure increases, although counterintui-
tive, may improve cerebral ischemia in animal studies.17
Ischemia improves with the enhancement of venous pressure
in humans, too, as recently demonstrated in 2 case reports in
which clinical improvement and middle cerebral artery flow
velocity increases were observed after creation of upper body
venous congestion with chest-high antigravity suit inflated
with 10 to 20 mm Hg pressure.18The effects of phenylephrine
on blood flow in poststroke perifocal penumbra suggest that
mild induced hypertension increases collateral cerebral blood
flow and oxygenation and improves cerebral metabolic rate
of oxygen in both the core and the penumbra. Shin et al19
induced hypertension with phenylephrine infusion starting 10
or 60 minutes after ischemia to increase blood pressure by
30% for the duration of ischemia. Similarly, Chi et al20
demonstrated that acute phenylephrine infusion increased the
number of veins with SvO2?40% in a rat model of middle
cerebral artery occlusion. Phenylephrine is an ?-1 adrenergic
agonist that constricts arterioles and directly increases after-
load and also redirects blood from bowel and muscle to the
central circulation and, as such, enhances cardiac preload and
cardiac output.21Central venous pressure increased during
infusion of phenylephrine in men.22An additional study by
Appleton et al23examined ?-adrenergic control of the venous
circulation in dogs in which heart rate was controlled with
atropine. To eliminate reflex changes in vascular tone, 8 dogs
received ganglionic blockade with trimethaphan. Increased cen-
tral blood volume resulted in an increase of mean circulatory
filling pressure and, as such, pressure gradients for venous return
(P?0.025). These authors concluded that phenylephrine reduces
peripheral vascular capacitance and shifts blood from peripheral
to the central vascular compartment. Phenylephrine, similar to
partial aortic occlusion, therefore may cause a redistribution of
blood volume rather than augmentation of blood flow through
arterial hypertension.
In summary, one must consider the venous effects of any
direct arterial intervention because hemodynamics results
from complex interactions among all aspects of the vascular
system. Future vascular approaches for acute occlusion of an
intracranial artery may be advanced by this conceptual
perspective. Furthermore, promising approaches such as par-
tial aortic occlusion may require further study to determine
optimal treatment protocols that enhance key venous effects.
Figure 1. Venous pressure augmentation affects
regional cerebral blood flow (rCBF) in 3 ways: (a)
like an Ohm resistor in the regions with normal tis-
sue pressure (external tissue pressure [Pe]?0):
flow decreases proportional to venous pressure
(Pv) and stops when Pv equals arterial pressure
(Pa); (b) like a Starling resistor in the regions with
homogeneously increased tissue pressure (Pe ?0,
spatially homogenous): flow decreases only when
Pv exceeds Pe; and (c) like a Starling resistor with
steal in the regions with heterogeneously
increased tissue pressure (Pe ?0, spatially hetero-
geneous): flow is diverted to the pathway of least
resistance (Pe?0). When inflow resistance (Ri) is
high, pressure at microcirculation level Pi
decreases and flow completely ceases when
inflow pressure (Pi) ?Pe. Increasing Pv augments
Pi and re-establishes flow when Pi ?Pe. This is
marked as point of no reflow (PONR): minimal
venous pressure required to re-establish flow in
the compressed regions. Regional flow is maxi-
mized when Pv reaches Pe. Further increase in Pv
decreases regional flow to the same extent as in
Ohm or Starling resistors. Pa is scaled to 100. Pv
varied from 0 to Pa. Pi is at the level of
microcirculation.
Figure 2. Arterial pressure increase does not augment
regional cerebral blood flow (rCBF) in regions with venous
steal until venous pressure exceeds point of no reflow
(PONR), ie, minimal venous pressure required to re-establish
flow in the presence of steal.
Pranevicius et al Venous Effects of Partial Aortic Occlusion
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Sources of Funding
This work has been funded by NIH-NINDS Awards K23 NS054084
(D.S.L.) and P50 NS044378 (D.S.L.).
Disclosures
D.S.L. is a scientific consultant regarding trial design and conduct
for Concentric Medical (modest) and CoAxia (modest).
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