Cerebral Blood Flow Is Determined by Arterial
Pressure and Not Cardiopulmonary Bypass
Flow Rate
Arthur E. Schwartz, MD, Aqeel A. Sandhu, MD, Richard J. Kaplon, MD,
William L. Young, MD, Amy E. Jonassen, MD, David C. Adams, MD,
Niloo M. Edwards, MD, Joseph J. Sistino, ccP, Pawel Kwiatkowski, MD, and
Robert E. Michler, MD
Departments of Anesthesiology and Surgery, College of Physicians and Surgeons, Columbia University, and Anesthesiology and
Surgery Services, Presbyterian Hospital in the City of New York New York New York
Background. D u r i n g c a r d i o p u l m o n a r y bypass, global
h y p o p e r f u s i o n of the b r a i n has been s h o w n to result in
ischemic insult and s u b s e q u e n t neurologic injury. Fur-
thermore, outcome after focal cerebral ischemia d e p e n d s
on collateral circulation, w h i c h is d e t e r m i n e d b y the
parameters of global perfusion. We therefore m e a s u r e d
cerebral b l o o d flow d u r i n g i n d e p e n d e n t m a n i p u l a t i o n s
of arterial b l o o d pressure and p u m p flow rate to deter-
m i n e which of these h e m o d y n a m i c parameters regulates
cerebral p e r f u s i o n d u r i n g c a r d i o p u l m o n a r y bypass.
Methods. Seven anesthesized b a b o o n s were placed on
c a r d i o p u l m o n a r y b y p a s s and cooled to 28°C. P u m p flow
rate and arterial b l o o d pressure were altered in varied
sequence to each of four conditions: (1) full flow (2.23 ±
0.06 L. m i n - 1 . m -2, m e a n ± standard deviation) at h i g h
pressure (61 ± 2 m m Hg), (2) full flow (2.23 ± 0.06
L- m i n -1 • m -2) at low pressure (24 ± 3 m m Hg), (3) low
'eurologic i n j u r y after c a r d i o p u l m o n a r y b y p a s s
N (CPB) resulting in cognitive dysfunction, stroke, or
death is an i m p o r t a n t complication of cardiothoracic
operations [1, 2]. I n a d e q u a t e global perfusion of the brain
d u r i n g b y p a s s has b e e n implicated as an i m p o r t a n t factor
in the etiology of this p r o b l e m [3-5]. Furthermore, out-
come from focal ischemia due to embolization or athero-
sclerotic cerebrovascular disease d e p e n d s on the ade-
quacy of collateral circulation, which is d e t e r m i n e d b y
the p a r a m e t e r s of global perfusion. During CPB clinical
m a n i p u l a t i o n s of p u m p flow rate a n d systemic arterial
b l o o d p r e s s u r e are e m p l o y e d routinely to preserve cere-
bral blood flow (CBF), because it is well established that
low p u m p flow concomitant with low arterial p r e s s u r e
results in d e c r e a s e d cerebral perfusion. However, the
i n d e p e n d e n t effects of arterial p r e s s u r e a n d p u m p flow
rate on CBF d u r i n g CPB are not u n d e r s t o o d clearly.
Accepted for publication March 22, 1995.
Presented in part at the Ninth European Congress of Anaesthesiology,
Jerusalem, Israel, October 2-7, 1994.
Address reprint requests to Dr Schwartz, Neuroanesthesia, Columbia
University, Rm 901, 161 Fort Washington Ave, New York, NY 10032.
© 1995 by The Society of Thoracic Surgeons
flow (0.75 L" m i n -1" m - 2 ) at h i g h p r e s s u r e (62 +
2 m m Hg), and (4) low flow (0.75 L. m i n - 1 . m - 2 at low
pressure (23 ± 3 m m Hg). D u r i n g each of these h e m o d y -
namic conditions cerebral b l o o d flow was m e a s u r e d b y
w a s h o u t of intracarotid xenon 133.
Results. Cerebral b l o o d flow was greater at h i g h b l o o d
pressure than at low pressure d u r i n g c a r d i o p u l m o n a r y
b y p a s s both at low flow (34 ± 8.3 versus 14.1 ± 3.7
mL" min -1 • 100 g-~) and full flow (27.6 ± 9.9 versus 16.8
± 3.7 m L . m i n - ~ ' 1 0 0 g-~) (p < 0.01). At comparable
m e a n arterial b l o o d pressures alteration of p u m p flow
rate p r o d u c e d no changes in cerebral b l o o d flow.
Conclusions. These results indicate that cerebral b l o o d
flow d u r i n g m o d e r a t e l y h y p o t h e r m i c c a r d i o p u l m o n a r y
b y p a s s is regulated b y arterial b l o o d pressure and not
p u m p flow rate.
(Ann Thorac Surg 1995;60:165-70)
Clinical studies have shown that m o d e r a t e changes in
p u m p flow rate or arterial p r e s s u r e result in either
m o d e r a t e or no changes in CBF [6-9]. Previous studies of
CPB in laboratory animals have not i n c l u d e d i n d e p e n -
dent m a n i p u l a t i o n of p r e s s u r e a n d p u m p flow rate.
Therefore, in a p r i m a t e m o d e l we investigated the i n d e -
p e n d e n t effects of arterial p r e s s u r e a n d p u m p flow rate
on CBF d u r i n g CPB, both within a n d b e l o w the h e m o d y -
namic limits of cerebral autoregulation.
Material and Methods
After a p p r o v a l b y the Institutional A n i m a l Care a n d Use
C o m m i t t e e of C o l u m b i a University, 7 adult b a b o o n s (5 to
15 kg) of either sex were studied. All animals received
h u m a n e care in compliance with the "Principles of Lab-
oratory A n i m a l C a r e " f o r m u l a t e d b y the National Society
for Medical Research a n d the " G u i d e for the Care a n d
Use of Laboratory A n i m a l s " p r e p a r e d b y the Institute of
Laboratory A n i m a l Resources a n d p u b l i s h e d b y the Na-
tional Institutes of Health (NIH publication 85-23, revised
1985).
A n e s t h e s i a was i n d u c e d with k e t a m i n e (10 mg/kg)
a d m i n i s t e r e d intramuscularly. Thereafter the trachea
0003-4975/95/$9.50
0003-4975(95)00357-Q
166 SCHWARTZ ET AL
CEREBRAL BLOOD FLOW DURING BYPASS
was i n t u b a t e d a n d ventilation controlled with oxygen
a n d isoflurane, 0.25% e n d - t i d a l concentration. Femoral
venous a n d arterial catheters were inserted. Fentanyl
(10 /~g/kg) was a d m i n i s t e r e d as an intravenous bolus,
followed by a continuous infusion of 2 t L g ' k g 1. h - l .
A d d i t i o n a l boluses of fentanyl were a d m i n i s t e r e d w h e n
indicated. M i d a z o l a m was a d m i n i s t e r e d intravenously at
a continuous rate of 0.03 m g - kg ~ • h 1. V e c u r o n i u m was
a d m i n i s t e r e d intravenously for n e u r o m u s c u l a r blockade.
Electrocardiogram, arterial b l o o d pressure, a n d tym-
panic, esophageal, a n d rectal t e m p e r a t u r e were r e c o r d e d
continuously. End-tidal carbon dioxide tension ( p C O 2 )
a n d isoflurane concentration were m e a s u r e d b y infrared
analysis (Datex CapnoMac, Helsinki, Finland). A n 18-
gauge n e e d l e was inserted into a l u m b a r intervertebral
space until cerebrospinal fluid was aspirated, after which
a thin Teflon catheter was t h r e a d e d into the subarach-
noid space.
After m e d i a n sternotomy, the right c o m m o n carotid
artery a n d its internal a n d external b r a n c h e s were ex-
p o s e d surgically. A 19-mm, 24-gauge Teflon catheter
(Angiocath; Becton Dickinson, Sandy, UT) was inserted
into the c o m m o n carotid artery, a n d p r e s s u r e s were
transduced. The ipsilateral external b r a n c h e s of the ca-
rotid artery were occluded t e m p o r a r i l y d u r i n g m e a s u r e -
m e n t of CBF. A thin catheter was inserted into the right
jugular vein a n d a d v a n c e d to the jugular bulb.
The s u p e r i o r vena cava, inferior vena cava, a n d aorta
were cannulated, a n d c a r d i o p u l m o n a r y b y p a s s was ini-
tiated. The b y p a s s circuit consisted of a Medtronic-
M i n i m a x oxygenator (Medtronic, Minneapolis, MN), a
BP-50 Centrifugal Bio-Pump (Medtronic), a n d 1/4-inch
tubing. The system was p r i m e d with 175 mL of Nor-
mosol-R a n d 175 mL of 6% H e s p a n (DuPont, W i l m i n g -
ton, DE). All surgical b l o o d loss was collected a n d pro-
cessed with a Cell Saver I (Haemonetics, Braintree, MA)
a n d then a d d e d to the b y p a s s circuit. H e p a r i n was
a d m i n i s t e r e d to maintain activated clotting time greater
than 480 seconds.
Nonpulsatile c a r d i o p u l m o n a r y b y p a s s was initiated at
a flow rate of 2.25 L . rain ~ • m 2, a n d b a b o o n s were then
cooled until t y m p a n i c m e m b r a n e t e m p e r a t u r e d e c r e a s e d
to 28°C. T y m p a n i c m e m b r a n e t e m p e r a t u r e has b e e n
shown to a p p r o x i m a t e brain t e m p e r a t u r e reliably [10]. At
that point, CPB p u m p flow rate a n d arterial b l o o d pres-
sure were altered in varied s e q u e n c e to each of four
conditions: (1) full flow (2.25 L" min - 1 . m 2) a n d m e a n
arterial p r e s s u r e of 60 m m Hg, (2) full flow (2.25
L- rain 1. m - 2 ) at arterial p r e s s u r e of 20 m m Hg, (3) low
flow (0.75 L- min 1 . m - 2 ) at arterial pressure of 60 m m Hg,
and (4) low flow at arterial blood pressure of 20 m m Hg.
Arterial p r e s s u r e was m e a s u r e d as m e a n p r e s s u r e trans-
d u c e d from the c o m m o n carotid artery catheter. Reduc-
tions in arterial b l o o d p r e s s u r e were achieved by sub-
a r a c h n o i d injection of lidocaine 2% solution. If a dose
sufficient to p r o d u c e spinal block d i d not result in the
target b l o o d pressure, n i t r o p r u s s i d e was a d m i n i s t e r e d as
an intravenous infusion. Elevations of arterial blood
p r e s s u r e were achieved b y variable tension on a snare
encircling the d e s c e n d i n g aorta. C h a n g e s in b y p a s s flow
Ann Thorac Surg
1995;60:165-70
rate were m a d e by varying the s p e e d of the centrifugal
p u m p . Arterial b l o o d gases were m e a s u r e d at 37°C,
i n d e p e n d e n t of b o d y t e m p e r a t u r e (alpha-stat blood gas
management).
Cerebral blood flow was m e a s u r e d before CPB a n d
during each of the four h e m o d y n a m i c conditions during
CPB. For each determination, 700 /~Ci of xenon 133 in
0.8 mL of saline solution was injected into the c o m m o n
carotid artery a n d flushed with 2 mL of normal saline
solution [11]. Single collimators directed at the superior
parietal cortex detected radioactive washout with a Novo
C e r e b r o g r a p h 10a (Novo Diagnostics Systems, Bags-
vaard, Denmark). Additional detectors were placed over
the aortic cannula to confirm the absence of significant
recirculation of isotope. Clearance was r e c o r d e d for at
least 12 minutes, and CBF was d e t e r m i n e d by the initial
slope, as described by Olesen a n d associates [12], fitting
a m o n o e x p o n e n t i a l decay curve to activity recorded from
the scalp for 60 seconds b e g i n n i n g 3 seconds after attain-
ing its p e a k value [13]. S p a h n and colleagues [14] have
v a l i d a t e d the technique of washout of arterial 133Xe
d u r i n g CPB by comparison with the m e t h o d of Kety-
Schmidt. Values for the blood-tissue partition coefficient
for 133Xe were corrected for hematocrit and t e m p e r a t u r e
[15]. Arterial and jugular venous samples were d r a w n
a n d analyzed at 37°C in a blood-gas analyzer a n d CO-
Oximeter (Instrumentation Laboratory, Lexington, MA).
Arterial a n d venous oxygen content were calculated by
s t a n d a r d formulas [16]. Cerebral metabolic rate for 0 2
was calculated as the product of CBF and the arterial-
venous oxygen content difference. Values for cerebral
b l o o d flow, arterial venous 02 content difference, cere-
bral oxygen metabolic rate, arterial blood pressure, he-
matocrit, arterial carbon dioxide tension and t e m p e r a t u r e
were c o m p a r e d by r e p e a t e d m e a s u r e s analysis of vari-
ance. Multiple comparisons were m a d e with Fisher's
protected least significant difference testing. A value of p
less than 0.05 was considered significant.
Results
The p r e d e t e r m i n e d h e m o d y n a m i c c o n d i t i o n s w e r e
achieved in all baboons. In 3 b a b o o n s nitroprusside was
a d m i n i s t e r e d after spinal block to reduce m e a n arterial
blood pressure to less than 30 m m Hg during full-flow
bypass. In I animal the full-flow p u m p rate was set at 2.1
L- rain 1. m- 2, which was the m a x i m u m rate achievable
without volume loading that w o u l d have resulted in
h e m o d i l u t i o n c o m p a r e d with previous bypass condi-
tions.
Temperature, arterial pCO2, arterial oxygen tension,
pH, a n d hematocrit were similar for all four h e m o d y -
namic conditions during CPB (Table 1). Cerebral blood
flow was greater at high blood pressure during both
low-flow and full-flow CPB w h e n c o m p a r e d with low
blood pressure at low-flow or full-flow CPB (34.0 _+ 8.3
a n d 27.6 ± 9.9 v e r s u s 14.1 ± 3.7 a n d 16.8 ± 3.7
m L - m i n - l . 1 0 0 g 1, respectively; p ~ 0.01) (Fig 1).
Changes in p u m p flow rate alone without changes in
m e a n arterial b l o o d pressure resulted in no change in
A n n Thorac S u r g S C H W A R T Z ET AL 167
1995;60:165-70 CEREBRAL B L O O D F L O W D U R I N G BYPASS

Table 1. Physiologic Variables Before and During Cardiopulmonary Bypass"

Full-Flow CPB Low-Flow CPB
Variable Before Bypass High BP Low BP High BP Low BP
CBF (mL. min -1 • 100 g-l) 26.0 ± 3.1 27.6 ± 9.9 16.8 ± 3.7b 34.0 ± 8.3 14.1 + 3.7b
A - V O 2 (mL/100 mL) 5.1 ± 1.7b 2.5 ± 1.3 3.0 ± 1.8 2.2 ~ 0.9 3.3 + 0.5
CMRO2 (mL • min -1 • 100 g-l) 1.2 +_ 0.4b 0.68 + 0.40 0.49 -+ 0.25 0.70 _+ 0.20 0.44 _+ 0.20
MABP (mm Hg) 69 ± 13 61 ± 2 24 ± 3 62 _+ 2 23 ± 3
Pump flow (L- min -1 • m -2) ... 2.23 ± 0.06 2.23 + 0.06 0.75 0.75
Temp (°C) 35 -+ 0.8 27.7 + 0.4 27.7 ± 0.5 27.7 ± 0.5 27.8 ± 0.4
p C O 2 (mm Hg) 33 ± 4 34 ± 2 33 ±2 36 ± 4 36 ± 3
pH 7.48 + 0.03c 7.42 + 0.04 7.43 ± 0.07 7.41 -+ 0.05 7.41 _+ 0.04
p O 2 (mm Hg) 499 ± 31~ 377 ± 128 382 ± 115 431 -+ 95 425 _+ 112
Hematocrit (%) 30 ± 3b 16 ± 4 16 ±4 16 -+ 3 16 ± 4

a Values are m e a n -+ s t a n d a r d deviation (n = 7); arterial blood gas analyses w e r e p e r f o r m e d at 37°C. b p < 0.01 c o m p a r e d with others, c p < 0.05
c o m p a r e d with others, a p < 0.05 c o m p a r e d with full-flow high BP, full-flow low BP, low-flow low BP.
A-VO2 = cerebral a r t e r i o v e n o u s oxygen content difference; BP arterial blood pressure; CPB = c a r d i o p u l m o n a r y bypass; CBF = cerebral
blood flow; C M R O 2 = cerebral oxygen metabolic rate; MABP = m e a n arterial blood pressure; p C O 2 ~ carbon dioxide tension; pO 2 =
oxygen tension.

CBF. C e r e b r a l a r t e r i a l - v e n o u s o x y g e n c o n t e n t differences t h a n CBF at the l o w e r p r e s s u r e , r e g a r d l e s s of p u m p flow

a n d c e r e b r a l m e t a b o l i c rates for o x y g e n w e r e similar for
all f o u r h e m o d y n a m i c c o n d i t i o n s of CPB.
C e r e b r a l a r t e r i o v e n o u s o x y g e n c o n t e n t difference, ce-
r e b r a l m e t a b o l i c rate for oxygen, a n d h e m a t o c r i t w e r e
h i g h e r b e f o r e h y p o t h e r m i c CPB t h a n d u r i n g all f o u r
c o n d i t i o n s d u r i n g h y p o t h e r m i c CPB.
Comment
O u r results i n d i c a t e t h a t arterial b l o o d p r e s s u r e a n d n o t
p u m p flow rate d e t e r m i n e s CBF d u r i n g h y p o t h e r m i c
CPB. C e r e b r a l b l o o d flow at h i g h e r p r e s s u r e w a s g r e a t e r
A
ol
8 40
e-
, ~
rate. F u r t h e r m o r e , w h e n m e a n arterial p r e s s u r e w a s
m a i n t a i n e d constant, c h a n g e s in p u m p flow rate did not
alter CBF. T h e h y p o t h e s i s that CBF is n o t d e t e r m i n e d b y
CPB p u m p flow rate was s u p p o r t e d b y m e a s u r e m e n t s
m a d e b o t h w i t h i n a n d b e y o n d t h e p r e s u m e d r a n g e of
pressure autoregulation.
P r e v i o u s studies of t h e d e t e r m i n a n t s of CBF d u r i n g
CPB h a v e y i e l d e d conflicting results. In a clinical s t u d y of
67 p a t i e n t s u n d e r g o i n g c o r o n a r y b y p a s s p r o c e d u r e s ,
G o v i e r a n d associates [17] m e a s u r e d CBF b y w a s h o u t of
a r t e r i a l 133Xe. C e r e b r a l b l o o d flow d i d n o t c o r r e l a t e w i t h
m e a n arterial b l o o d p r e s s u r e , w h i c h r a n g e d f r o m 30 to
110 m m Hg. N o r d i d CBF c o r r e l a t e w i t h b y p a s s flow rate,
w h i c h v a r i e d f r o m 1.0 to 2.2 L • m i n 1. m 2. In contrast,
S o m a a n d associates [18] s t u d i e d 21 a d u l t p a t i e n t s u n -
d e r g o i n g cardiac o p e r a t i o n s a n d r e p o r t e d that c e r e b r a l
p e r f u s i o n w a s directly d e p e n d e n t on p u m p flow rate. In
that study, CPB p u m p flow rate was v a r i e d r a n d o m l y to

E 70, 60, 50, a n d 40 m L - k g - 1 . m i n 1. As a result, CBF

-~ 30 values, m e a s u r e d by a m o d i f i e d K e t y - S c h m i d t m e t h o d
E e m p l o y i n g argon, d e c l i n e d from 43 to 35, 33, a n d 25
m L . m i n 1. 100 g - l , respectively. A l t h o u g h b l o o d pres-
.2 s u r e s m e a s u r e d at e a c h of t h e s e p u m p flow rates w e r e
m 20

1
n o t significantly different, b l o o d p r e s s u r e s w e r e n o t c o n -
o
_o t r o l l e d at c o n s t a n t values.
al V a n d e r L i n d e n a n d c o l l e a g u e s [19] also s u p p o r t e d t h e
10. c o n c l u s i o n t h a t p u m p flow rate a n d n o t p e r f u s i o n p r e s -
,1o s u r e d e t e r m i n e s c e r e b r a l b l o o d flow. T h e y r e p o r t e d t h a t
m i d d l e c e r e b r a l artery b l o o d flow velocity, m e a s u r e d by
0 t r a n s c r a n i a l D o p p l e r e c h o g r a p h y , in c h i l d r e n d u r i n g
0
0 20 30 40 50 60 70 d e e p h y p o t h e r m i c l o w - f l o w CPB c o r r e l a t e d w i t h p u m p
flow rate (r = 0.73) b u t n o t c e r e b r a l p e r f u s i o n p r e s s u r e
Mean Arterial Pressure (mm Hg) (r = 0.14).
Fig 1. Cerebral blood flow at low and high blood pressure during In a n o t h e r clinical study, M u r k i n a n d c o - w o r k e r s [20]
low-flow (open bars) and full-flow (solid bars) cardiopulmonary m e a s u r e d CBF b y 133Xe c l e a r a n c e in 38 cardiac s u r g e r y
bypass. (*Significantly different than at low blood pressure, p < patients. D u r i n g CPB, in w h i c h total flow rate w a s m a i n -
O.01.) t a i n e d b e t w e e n 2.0 a n d 2.5 L . m i n 1. m 2 m e a n c e r e b r a l
168 SCHWARTZET AL
CEREBRALBLOOD FLOW DURING BYPASS
perfusion p r e s s u r e s varying b e t w e e n 20 a n d 100 m m H g
d i d not correlate with CBF in the patient group for w h o m
arterial pCO2 was controlled b y alpha-star m a n a g e m e n t
( t e m p e r a t u r e - c o r r e c t e d p C O 2 k e p t at 27 m m Hg). How-
ever, in the p H - s t a t - m a n a g e d patients ( t e m p e r a t u r e -
corrected p C O 2 k e p t at 40 m m Hg) CBF was correlated
with c e r e b r a l p e r f u s i o n p r e s s u r e s b e t w e e n 15 a n d
95 m m Hg. A l t h o u g h Murkin a n d co-workers did main-
tain p u m p flow rate at values b e t w e e n 2.0 a n d 2.5
L . r a i n - i ' m 2, they did not control or i n d e p e n d e n t l y
m a n i p u l a t e arterial b l o o d p r e s s u r e as part of the study
design.
In contrast, Rogers a n d colleagues [6] i n d e p e n d e n t l y
m a n i p u l a t e d b l o o d p r e s s u r e b y infusing p h e n y l e p h r i n e
in patients d u r i n g CPB to elevate b l o o d p r e s s u r e delib-
erately while m a i n t a i n i n g a constant p u m p flow rate of
2.0 L - r a i n 1. m - 2 . In patients for w h o m arterial p C O 2
was a l p h a - s t a t m a n a g e d ( t e m p e r a t u r e - u n c o r r e c t e d p C O 2
= 40 m m Hg) deliberate elevation of m e a n arterial
p r e s s u r e from 56 + 7 to 84 ± 8 m m H g did not change
CBF, as m e a s u r e d b y 133Xe clearance. In the p H - s t a t -
managed group (temperature-uncorrected pCO 2 =
57 m m Hg), raising m e a n arterial blood p r e s s u r e from 53
± 8 to 77 ± 9 m m H g increased CBF b y 41%. In a
s u b s e q u e n t s t u d y of parallel design using s o d i u m nitro-
p r u s s i d e to reduce arterial b l o o d p r e s s u r e deliberately,
Rogers a n d colleagues [7] reported that a reduction in mean
arterial pressure from 75 ± 5 to 54 ± 5 m m Hg did not
reduce CBF in patients for w h o m p C O 2 w a s alpha-stat
m a n a g e d (temperature-uncorrected p C O 2 = 42 m m Hg).
However, in p H - s t a t - m a n a g e d patients (temperature-
uncorrected pCO 2 = 60 m m Hg), CBF decreased when
m e a n arterial pressure was reduced deliberately from 76 ±
9 to 50 ± 6 m m Hg. In both studies p u m p flow rate was held
constant while blood pressure was altered independently.
In a subsequent clinical study, Rogers and colleagues [8]
r a n d o m l y v a r i e d p u m p flow rate to 1.75 a n d 2.25
L ' m i n - 1 - m -2 a n d noted no associated s p o n t a n e o u s
changes in systemic blood pressure. Cerebral blood flows at
these two p u m p flow rates were similar. In all the work of
this group these deliberate changes in blood pressure and
p u m p flow were relatively moderate and did not transcend
the limits of cerebral autoregulation where risk of neuro-
logic injury is p r e s u m e d greatest.
Most recently, in a large clinical study, m o d e r a t e in-
creases or decreases in m e a n arterial blood p r e s s u r e
(between 51 a n d 75 m m Hg) d u r i n g a l p h a - s t a t - m a n a g e d
CPB were shown to result in small p r o p o r t i o n a l changes
in CBF (0.86 m L . m i n 1.100 g ~ for every 10 m m H g
change in pressure) w h e n b y p a s s p u m p flow rate was
k e p t constant [9]. The m u c h greater p r o p o r t i o n a l changes
in CBF with changes in b l o o d p r e s s u r e r e p o r t e d in our
s t u d y indicates that autoregulation of cerebral blood flow
is i m p a i r e d s u b s t a n t i a l l y at b l o o d p r e s s u r e s n e a r
20 m m Hg.
In multiple studies involving animal m o d e l s of CPB,
reductions in p u m p flow rate p r o d u c i n g decreases in
systemic arterial blood p r e s s u r e have resulted in de-
creases in cerebral perfusion. Fox a n d associates [21]
v a r i e d CPB p u m p flow rate to four different values
Ann Thorac Surg
1995;60:165-70
b e t w e e n 0.25 a n d 1.75 L . r a i n - 1 m~-2 in cynomolgus
m o n k e y s a n d m e a s u r e d CBF by injection of radioactive
microspheres. As p u m p flow declined from 1.5 to 1.0 to
0.5 L . min 1. m 2 m e a n arterial pressure declined from
32.8 to 24.5 to 16.3 m m Hg, and CBF declined from 45 to
41 to 23 m L . m i n 1. 100 g 1, respectively. Similarly,
Tanaka and colleagues [22], in a dog m o d e l of CPB where
CBF was d e t e r m i n e d by venous outflow from the isolated
sagittal sinus, sequentially lowered p u m p flow rate to
obtain perfusion pressures ranging from 90 to 20 m m Hg.
W h e n p u m p flow rate declined so as to p r o d u c e perfu-
sion pressures less than 40 m m Hg, decreases in arterial
p r e s s u r e p r o d u c e d m a r k e d decreases in CBF. In rabbits,
Hindrnan and co-workers [23] varied CPB p u m p flow rate
to 50, 70, a n d 100 m L . k g l . m i n 1. Each decrease in
p u m p flow rate p r o d u c e d a decrease in m e a n arterial
pressure resulting in d e c r e a s e d CBF, as m e a s u r e d by
microspheres.
O u r study design is u n u s u a l for its i n d e p e n d e n t ma-
nipulation, over wide ranges, of b y p a s s p u m p flow a n d
systemic arterial pressure. Spinal blockade and variable
constriction of the d e s c e n d i n g aorta were e m p l o y e d to
limit pharmacologic agents that might affect cerebral
vascular tone directly. Although s o d i u m nitroprusside,
e m p l o y e d in 3 animals, m a y have caused some dilation
of cerebral resistance vessels [24], CBF values in these
animals were no different than in animals whose blood
p r e s s u r e was d e c r e a s e d with spinal blockade alone. Fur-
thermore, CBF during full flow at low pressure, w h e n 3
animals received nitroprusside, was not higher than CBF
d u r i n g low flow at low pressure w h e n no nitroprusside
was administered. Although elevation of blood pressure
b y constriction of the aorta m a y divert blood flow pref-
erentially to the brain, this is exactly what is accom-
plished with any alternate technique (mechanical, p h a r -
m a c o l o g i c , or p h y s i o l o g i c ) t h a t i n c r e a s e s s y s t e m i c
vascular resistance. Aortic constriction raises arterial
p r e s s u r e without a direct effect on cerebral vascular tone.
Phenylephrine, for example, w o u l d increase systemic
vascular resistance, divert blood preferentially to the
brain, a n d p e r h a p s alter cerebrovascular tone directly.
In conclusion, cerebral blood flow during hypothermic
CPB is regulated by arterial blood pressure and not
p u m p flow rate. In clinical practice, m a n a g e m e n t of CPB
should be directed at m a i n t a i n i n g arterial blood pressure
at both high and low p u m p flow rates to preserve
perfusion of the brain.
Supported in part by National Institutes of Health grant RO1-NS
27713.
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INVITED COMMENTARY
The u n i q u e circumstances of cardiopulmonary bypass
allow a greater degree of control over the systemic
circulation than is f o u n d in virtually a n y other clinical
situation. Essentially all aspects of perfusion, such as
selection of pulsatile or l a m i n a r flow characteristics,
hypothermic or n o r m o t h e r m i c temperatures, hematocrit,
high or low flow rates, a n d perfusion pressures that are
within or below the autoregulatory range, are deter-
m i n e d either specifically or routinely by the clinician.
Most of these clinical d e t e r m i n a n t s have b e e n adopted
empirically based on more than 40 years of accumulated
clinical experience. However, in an era that has seen pa-
tients who are increasingly at the extremes of age, and who
are undergoing procedures of progressively greater length
and complexity, the incidence of adverse neurologic events
after cardiopulmonary bypass has risen substantially. To
what extent hypoperfusion is contributing to this cerebral
morbidity is unclear, but it is apparent that a greater
understanding of the specific factors influencing cerebral
physiology during cardiopulmonary bypass is essential.
SCHWARTZET AL 169
CEREBRALBLOOD FLOWDURINGBYPASS
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Tissue-blood partition coefficient for xenon: temperature
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16. Prough DS, Rogers AT, Stump DA, et al. Cerebral blood flow
decreases with time whereas cerebral oxygen consumption
remains stable during hypothermic cardiopulmonary bypass
in humans. Anesth Analg 1991;72:161-8.
17. Govier AV, Reves JG, McKay RD, et al. Factors and their
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18. Soma Y, Hirotani T, Yozu R, et al. A clinical study of cerebral
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19. Van der Linden J, Priddy R, Ekroth R, et al. Cerebral
perfusion and metabolism during profound hypothermia in
children: a study of middle cerebral artery ultrasonic vari-
ables and cerebral extraction of oxygen. J Thorac Cardiovasc
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20. Murkin JM, Farrar JK, Tweed WA, McKenzie FN, Guiraudon
G. Cerebral autoregulation and flow/metabolism coupling
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21. Fox LS, Blackstone EH, KirklinJW, Bishop SP, Bergdahl LAL,
Bradley EL. Relationship of brain blood flow and oxygen
consumption to perfusion flow rate during profoundly hy-
pothermic cardiopulmonary bypass: an experimental study.
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22. Tanaka J, Shiki K, Asou T, Yasui H, Tokunaga K. Cerebral
autoregulation during deep hypothermic non-pulsatile car-
diopulmonary bypass with selective cerebral perfusion in
dogs. J Thorac Cardiovasc Surg 1988;95:124-32.
23. Hindman BJ, Funatsu N, Harrington J, et al. Differences in
cerebral blood flow between alpha-stat and pH-stat man-
agement are eliminated during period of decreased systemic
flow and pressure: a study during cardiopulmonary bypass
in rabbits. Anesthesiology 1991;74:1096-102.
24. Michenfelder JD. Cerebral blood flow and metabolism. In:
Cucchiara RF, Michenfelder JD, ed. Clinical neuroanesthe-
sia. New York: Churchill Livingstone, 1990:28-9.
In the hypothermic c a r d i o p u l m o n a r y bypass model
employed by Schwartz a n d associates, changes in m e a n
arterial pressure below the a p p a r e n t cerebral autoregu-
latory range were shown to influence cerebral blood flow
directly. Conversely, profound reductions in p u m p flow
rate produced no significant effects on cerebral blood
flow. Other studies, both clinical and experimental, have
suggested such effects, b u t generally either the variables
in these studies were altered over a fairly limited range or
flow rate a n d perfusion pressure interacted a n d were not
kept as totally i n d e p e n d e n t variables. Now that Schwartz
a n d associates effectively have confirmed the primacy of
perfusion pressure over flow rates, the clinical implica-
tions of this information, a n d the implications for further
investigations, should be considered.
Clinically, these data suggest that w h e n flow reduc-
tions are required d u r i n g c a r d i o p u l m o n a r y bypass, ef-
forts must be made to m a i n t a i n cerebral perfusion pres-
sure to preserve cerebral blood flow. Similarly, even
w h e n hypotension is accompanied by high p u m p flow
 170 SCHWARTZET AL
CEREBRALBLOOD FLOW DURINGBYPASS
r a t e s - - s u c h as s o m e t i m e s occurs d u r i n g n o r m o t h e r m i c
c a r d i o p u l m o n a r y b y p a s s - - a d e q u a c y of cerebral perfu-
sion cannot be assumed. W h a t specifically that perfusion
pressure should be has not yet b e e n addressed. Also, the
larger question of w h e t h e r the limits of cerebral autoreg-
ulation are e x t e n d e d during m o d e r a t e h y p o t h e r m i c car-
d i o p u l m o n a r y bypass, as several clinical studies have
suggested, remains unclear. From the data of Schwartz
and associates, cerebral autoregulation does a p p e a r to be
lost at extremes of hypotension. As such, it w o u l d a p p e a r
that the clinician cannot blithely accept hypotension,
even during h y p o t h e r m i a with high flow rates, with any
confidence of maintaining a d e q u a t e cerebral blood flow.
REVIEW OF RECENT BOOKS
Case Reports I, Clinical Studies in Extracorporeal Circulation
Edited by Trudy B. Stafford, John M. Toomasian, and Mark Kurusz
Houston, PREF Press, 1994
250 pp, not illustrated, $50.00
Reviewed by Edward Y. Sako, MD, PhD
This book represents a compilation of case reports presented at
meetings of the American Society of Extracorporeal Technology
and the newly formed Perfusion Research and Education Foun-
dation in 1992 and 1993, respectively. Each chapter represents a
separate case report, including a presentation as was given at
the meeting, followed by a verbatim transcript of the discussion
that followed. The chapters themselves are organized into sec-
tions entitled Patient Pathophysiology, Hematogic Aspects, Me-
chanical Problems, Extracorporeal Membrane Oxygenation,
Ventricular Assist, Nonroutine Applications, Cardiopulmonary
Support, and Legal Considerations.
© 1995 by The Society of Thoracic Surgeons
Ann Thorac Surg
1995;60:165-70
By default, maintaining pressures at the normal lower
limit of cerebral autoregulation--50 m m H g - - a p p e a r s
judicious. Cerebral perfusion pressure must be main-
tained.
John M. Murkin, M D
Department of Anaesthesia
University Hospital
University of Western Ontario
London, Ontario, Canada
N6A 5A5
As for the format, the case reports vary widely in terms of
organization and presentation. In some instances they are diffi-
cult to follow. There are no illustrations provided, although in
many cases this would be extremely helpful in terms of under-
standing the actual apparatus set up. Although the book does
give some indication of the increasing breadth and application
of extracorporeal circulation technology, the content and focus
clearly are aimed at perfusionists. There is minimal background
and detail regarding the actual surgical procedures. The result is
to limit the interest and usefulness the book may have for the
practicing cardiothoracic surgeon. Certainly, an extremely good
understanding of extracorporeal circulation technology is nec-
essary, but this probably is better served by the more standard
reference texts.
San AntoniG Texas
0003-4975/95/$9.50
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