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1Departments of Physiology and Biophysics,2 Clinical Neurosciences, and3 Community Health Sciences, Faculties of Medicine and4 Kinesiology, University of Calgary, Calgary, Alberta, Canada T2N 4N1
Submitted 23 December 2002 ; accepted in final form 12 March 2003
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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cerebral blood flow; hyperventilation
20 Torr) and hypercapnia (greather than 100
Torr), whereas the CBF-PaCO2 relationship appears to be
rather linear in the range of PaCO2 from 20 to
60 Torr (27). In humans,
some studies have been consistent with a linear CBF response across both the
hypocapnic and hypercapnic ranges of PETCO2
(9), whereas other studies have
not (7,
26) and have instead suggested
that the relationship is better described by exponential
(15) or sigmoidal
(28) functions. Although CBF
is reduced with acute hypocapnia
(23), CBF returns toward
normal values over a period of minutes despite PaCO2 or
end-tidal PCO2 (PETCO2)
being kept constantly low (23,
32). The presence of a slow
adaptive process in the CBF response to hypocapnia
(23) may help explain why
there is uncertainty as to whether the CBF response is linear with variations
in PETCO2 from 20 to 50 Torr in
humans.
The previous studies in humans were based on two or three distinct levels
of PETCO2 and did not provide a complete
description of the CBF response over the range of
PETCO2 from 20 to 50 Torr. Thus the
aim of this study was to further extend the previous findings in human studies
by measuring the CBF sensitivity to variations in
PETCO2 throughout the range of
PETCO2 from hypocapnia to hypercapnia.
Furthermore, Poulin et al.
(22,
23) previously reported the
presence of an undershoot or an overshoot in CBF when
PETCO2 is returned to eucapnic levels after a
sustained period of hypercapnia
(22) and hypocapnia
(23), respectively. The reason
for the overshoot and undershoot is unclear but may reflect an alteration or
adaptation in the mechanisms underlying the vasodilation and vasoconstriction
of cerebral vessels by hypercapnia and hypocapnia, respectively. Thus a
secondary objective of this study was to investigate the hypothesis that the
CBF response to alterations in PETCO2 is
different when PETCO2 is incremented from
hypocapnia to hypercapnia than when PETCO2 is
decremented from hypercapnia to hypocapnia.
Cerebral perfusion was evaluated by using transcranial Doppler ultrasound (TCD), and end-tidal gases were controlled by using the technique of dynamic end-tidal forcing. TCD is a noninvasive tool for the evaluation of cerebral perfusion with the advantage of near-continuous recordings. Moreover, use of the dynamic end-tidal forcing technique enables the control of PETCO2 and end-tidal PO2 (PETO2) precisely, despite the variations in the ventilatory responses resulting from changes in the arterial blood gases. Therefore, this allows the examination of steady-state CBF responses to each level of PETCO2. Together, these techniques are well-suited for the evaluation of CBF responses to alterations in PETCO2 in humans.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Protocols. The laboratory is located at 1,103 m above sea level,
and the average barometric pressure for the study days in this experiment was
660 Torr. The subjects visited the laboratory on three occasions. The
first day served as a session for familiarization to the apparatus for all
participants. On the second and third visits, the main study was conducted. On
each of these visits, the subject's normal
PETCO2 and
PETO2 were measured before the experiment,
while the subject was sitting quietly and comfortably for 10 min. In
brief, respired gas was sampled via a fine catheter held at the opening of one
nostril by an adapted nasal O2 therapy kit. The gas was sampled
continuously at a rate of 20 ml/min and analyzed for PO2
and PCO2 by mass spectrometer (AMIS 2000, Innovision,
Odense, Denmark). Values for PO2 and
PCO2 were sampled by computer every 10 ms.
PETO2 and
PETCO2 were identified and recorded for each
breath by using a computer and dedicated software (Chamber version 1.00,
University Laboratory of Physiology, Oxford, UK).
For the main study, two protocols were employed on each day: a CO2-incrementing protocol (protocol I) and a CO2-decrementing protocol (protocol D). Both protocols were performed on each subject, with the order randomly assigned and a 45-min recovery period between each protocol. The technique of dynamic end-tidal forcing was used to control PETCO2 and PETO2 (see Hyperventilation and control of PETCO2). In both protocols, PETO2 was held constant at 100 Torr throughout the experiments. Initially, PETCO2 was held at 1.5 Torr above the subject's normal value for 8 min. This was done because the technique of dynamic end-tidal forcing can add but cannot remove CO2 from the inspirate. Thus, by adding a small amount of CO2 to the inspirate, it is possible to regulate PETCO2 to hold it at the desired level. Otherwise, if the actual PETCO2 rises slightly above the desired level (for example, if the normal PETCO2 value is underestimated) and if there is no CO2 in the inspirate, the control of PETCO2 becomes ineffective. In protocol I, PETCO2 was then decreased in one step by 16 Torr and was stabilized for 2 min. PETCO2 was then increased in stepwise increments of 2 Torr every 2 min up to 10 Torr above the subject's normal value. In protocol D, PETCO2 was increased in one step by 10 Torr and was stabilized for 4 min. PETCO2 was then reduced in a stepwise manner by 2 Torr every 2 min to a value of 16 Torr below the subject's normal value. Finally, PETCO2 was returned in one step to its initial near-eucapnic value and maintained at this value for a further 5 min.
Hyperventilation and control of PETCO2. Each experimental protocol was initiated with a 3-min period with the subject breathing normally through a mouthpiece with the nose occluded by a nose clip. Thereafter, the subject followed a constant pattern of hyperventilation. This controlled hyperventilation enabled the technique of dynamic end-tidal forcing to stabilize the subject's PETCO2 at the desired level by changing the inspired PCO2 level. A frequency of one breath every 3 s was dictated by an audio alarm, and visual feedback was provided with an oscilloscope that reflected the inspired tidal volume to keep the volume relatively constant throughout. Subjects were allowed to breathe at their own pace only if it was difficult to keep the pace during the highest level of hypercapnia. After the cessation of hypocapnia or hypercania, subjects were allowed to breathe normally for the remainder (i.e., 5 min) of the experiment.
The inspired and expired gases were sampled at a rate of 20 ml/min and analyzed by mass spectrometer for fractional concentrations of O2 and CO2. Respiratory volumes and flow information were obtained by using a pneumotachograph and differential pressure transducer (RSS100-HR, Hans Rudolph, Kansas City, MO). Respiratory flow direction and timing information were measured with a turbine volume transducer (VMM-400, Interface Associates). A computer sampled the experimental variables every 10 ms. Accurate control of the end-tidal gases was achieved by using the technique of dynamic end-tidal forcing (BreatheM version 2.07, University Laboratory of Physiology, Oxford, UK). A controlling computer generated the inspired partial pressure of O2 and CO2 predicted to give the desired end-tidal partial pressures by using a fast gas-mixing system (11, 23, 29). The controlling computer received feedback of the measured end-tidal partial pressures on a breath-by-breath basis as the experiment progressed. These measured end-tidal values were compared with the desired values, and the computer then adjusted the initial predicted inspired gas mixture by using an integral proportional feedback algorithm based on the deviations of the measured end-tidal values from the desired end-tidal values (11, 23, 29).
TCD. Backscattered Doppler signals from the right MCA were
measured by using a 2-MHz pulsed Doppler ultrasound system (TC22, SciMed,
Bristol, UK). The MCA was identified by an insonation pathway through the
right temporal window just above the zygomatic arch by using search techniques
described previously (22,
23). This procedure was
repeated on each visit. The insonation depth (the distance from the probe to
the start of the Doppler sample volume) was set initially at a depth of
50 mm, and then a short search procedure began by varying the angle and
position of the probe to identify a window that provided Doppler spectra from
the MCA. The sample depth was then increased in an increment of 1 mm until the
quality of the Doppler spectra from the MCA became poor (65 mm). At this
point, the sample depth was decreased in an increment of 1 mm to a depth of
45 mm. At each depth, a short search was performed by making small
adjustments to the angle and position of the probe to assess the relative
magnitude of the total Doppler power along with the quality of the Doppler
spectra. The sample was then returned to the depth at which the Doppler signal
was maximal, and at that depth the angle and position of insonation was
adjusted to provide the signal with maximum power. The center of this position
was identified with a waterproof marker directly on the skin. The Doppler
probe was removed, and ultrasonic gel (Aquasonic 100, Parker Laboratories,
Fairfield, NJ) was reapplied to the probe, which was then secured with a
headband device (Müller and Moll Fixation, Nicolet Instruments, Madison,
WI). The Doppler probe was securely positioned in this headband device to
maintain the optimal insonation position and angle.
During a first visit (familiarization), the optimal position of the Doppler probe was identified, and a tracing of this position was made by using a plastic transparency with the marker to delineate the contour of the Doppler probe fixture and the headband device. This tracing served to establish the precise position of the headband device for the subsequent visits. To maintain the insonation position and angle between the experimental sessions within each visit, the Doppler probe was not removed from or adjusted within the headband device. The Doppler system was adapted by the manufacturer to make the Doppler signals available as analog signals sampled every 10 ms. Signals for maximum and intensity-weighted mean Doppler frequency shifts were available as analog signals and were updated each time a new spectrum was calculated every 10 ms. In this study, the maximum frequency of Doppler shift, namely, peak blood velocity (Vp) was taken as the primary index of CBF (24).
Analysis. To average Vp over larger periods of
time, Vp was first averaged over each heart beat to give
the beat-by-beat values
(
p). Likewise, the data
for PETCO2 were determined for each breath to
give breath-by-breath values. The beat-by-beat and breath-by-breath data were
further averaged to give one value over each 15-s period. For the statistical
analysis, the 15-s data were averaged to give values for a 3-min baseline
period before the onset of the CO2 stimulus and for the last 30 s
of each 2-min PETCO2 step. In addition to
calculating absolute values, normalized beat-by-beat and breath-by-breath
values were calculated for
p and
PETCO2, respectively. For
p, the 3-min baseline
period was normalized to 100% and used to calculate the percent change over
time in p for the duration
of the experiment. For PETCO2, the data over
the 3-min baseline period were expressed as deviations from the baseline value
and used to calculate the difference between the measured
PETCO2 and the baseline eucapnic
PETCO2
(
PETCO2). The beat-by-beat and
breath-by-breath normalized data were also averaged to give one value every 15
s. Similar to the absolute data, the 15-s normalized data were averaged to
give values for baseline and for the last 30 s of each step in
PETCO2.
Regression models. To determine the mathematical model that best
described the CBF-PETCO2 relationship,
several regression equations were fit with
p as the dependent
variable and PETCO2 as the independent
variable. Before fitting the equations, the mean of the two repetitions for
each subject was calculated for both protocol I and protocol
D, thus providing one set of data for each subject per protocol.
Calculating the mean to reduce the number of observations was a reasonable
approach because the level of agreement (i.e., reproducibility) between the
repetitions among subjects was very high. The level of agreement was assessed
by the intraclass correlation coefficient, which has a range of values from 0
(no agreement) to 1 (perfect agreement). The level of agreement was 0.93 for
p and 0.99 for
PETCO2 in protocol I and 0.95
for p and 0.99 for
PETCO2 in protocol D. Thus
the means for p and
PETCO2 of the last 30 s of each of the 14
PETCO2 steps were determined for each
subject, and the data set for the regression analyses consisted of 112 pairs
(14 steps by 8 subjects) of normalized values of
p and
PETCO2 for each protocol.
Three regression models were considered. The first was a simple linear
model, written as
 | (1) |
p (%),
x is PETCO2 (Torr), and
a and b are regression parameters (a = intercept,
b = slope). The CBF-PETCO2 relationship has previously been described as consisting of two different components, one above and the other below eucapnia. Thus the second regression model consisted of a piecewise linear model, with the first piece corresponding to the data in the eucapnia-hypocapnia range and the second piece in the eucapnia-hypercapnia range. Both pieces were written in the form of Eq. 1 above.
Finally, a nonlinear exponential regression model was considered. This
model was written as
 | (2) |
p (%),
x is PETCO2 (Torr),
a and b are regression parameters. In this model, the
sensitivity of CBF for a given PETCO2
was described by the first derivative, which can be written as
 | (3) |
Statistics. A Student's t-test was performed to assess
differences in the steady-state levels of
PETCO2 between protocols I and
D. To assess the effect of protocol on the relationship between
p and
PETCO2, a multiple-partial F test
was performed. An indicator variable was added to the regression model to
differentiate between data from protocols I and D. The
strength of the relationship between
p and
PETCO2 in each of the three regression
models was evaluated by using a coefficient of determination
(R2). A statistical test of coincidence and of parallelism
(17) was used to assess
whether the regression models describing protocols I and D
were coincidental and parallel. The very nature of the test of parallelism is
to determine whether the two slopes (i.e., curves) are equal. Therefore, if
the two slopes are different, then the two curves are not parallel. The nature
of the test of coincidence is to determine simultaneously whether the two
slopes and intercepts are equal. Therefore, if the two slopes and intercepts
are different, then the two curves do not cross the y-axis at the
same point and are not parallel.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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CBF responses
toPETCO2.
Table 1 shows the group means
for PETCO2,
PETCO2,
PETO2,
p (absolute values in
cm/s; normalized values in % of baseline) at baseline eucapnia, the lowest
PETCO2 in hypocapnia, and the highest
PETCO2 in hypercapnia during protocols
I and D. Figure 2
illustrates temporal profiles of the percent change from baseline in
p and
PETCO2.
Figure 3 illustrates the
individual data of the percent changes (from baseline) in
p as a function of
PETCO2.
Figure 4 illustrates the
relationship between percent change from baseline in
p as a function of
PETCO2 during protocols I and
D for all subjects. In protocol I,
p at baseline eucapnia was
58.3 ± 7.8 cm/s and decreased to 60.8 ± 4.9% (35.2 ± 4.6
cm/s) with the lowest PETCO2 (38.4 ±
2.3 to 23.0 ± 1.4 Torr; Table
1). Then, the increases in
p followed the increases
in PETCO2. With the highest
PETCO2 (48.7 ± 1.8 Torr),
p was increased to 151.8
± 8.9% (88.3 ± 13.5 cm/s). In protocol D,
p was increased to 149.2
± 12.1% (59.1 ± 8.3 to 88.1 ± 15.4 cm/s) with the highest
PETCO2 (38.3 ± 2.3 to 48.9 ±
2.0 Torr; Table 1). Then, the
decrease in p followed the
decreases in PETCO2. With the lowest
PETCO2 (22.4 ± 1.7 Torr),
p was decreased to 69.1
± 5.3% (40.7 ± 5.2 cm/s). With the lowest
PETCO2, the absolute value for
p was smaller in
protocol I than it was in protocol D (P = 0.005),
although the level of PETCO2 was comparable
between protocols.
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A test of carry-over effect
(30) was used to assess
whether a subject's response in the second protocol was altered by lingering
aftereffects from the first protocol. A test of carry-over effect yielded
P values of 0.74 for
p and 0.94 for
PETCO2, implying the absence of a
carry-over effect. In other words, the order in which protocols I and
D were administered to the subjects did not affect the results.
Comparison of coefficients of determination for the regression models
describing the CBF-PETCO2
relationship. Table 2
shows the coefficients of determination and regression parameter estimates for
the one-linear, two-linear, and exponential regression models for the
CBF-PETCO2 relationship in protocols
I and D. On the basis of R2, the exponential
model was the best-fitting model and is illustrated in
Fig. 4. A test of coincidence
and of parallelism using a multiple-partial F test indicated that the
regression models describing protocols I and D were
noncoincident (P < 0.001) and were not parallel (P =
0.003). This is evident from Fig.
4, where the fitted regression lines share a common point in
hypocapnia and then diverge as PETCO2
increases.
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CBF-PETCO2 sensitivity:
predictions based on models. Table
3 shows the predicted CBF-PETCO2
sensitivity determined from one- and two-linear, and exponential models at
PETCO2 of -20, -16, -10, 10, and 20
Torr. The two-linear regression model implies that the
CBF-PETCO2 sensitivity would be altered with
the transition at eucapnia, i.e., CBF-PETCO2
sensitivity above eucapnia is higher than that below eucapnia. With the
exponential model, the CBF-PETCO2 sensitivity
would change continuously throughout the range of
PETCO2. The exponential model indicates that
the CBF-PETCO2 sensitivity would increase
from 2.1 to 4.7%/Torr in protocol I and from 1.9 to 4.0%/Torr in
protocol D in the range of PETCO2
from 16 Torr below eucapnia to 10 Torr above eucapnia.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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20 to 50 Torr in humans. The major findings are that
1) CBF closely follows the alterations in
PETCO2 throughout the range of
PETCO2 studied; 2) the sensitivity
of CBF to the changes in PETCO2 is nonlinear,
with a greater sensitivity in the hypercapnic range compared with the
hypocapnic range, and the relationship between CBF and
PETCO2 appears to be best described by
an exponential regression model; and 3) there is evidence of
hysteresis in the CBF-PETCO2 relationship,
with the sensitivity of CBF being greater during an incremental protocol
compared with a decremental protocol for a given
PETCO2.
CBF response curve in the range of PCO2 from 20
to 50 Torr. In a study by Reivich
(27), the CBF response in the
range of PaCO2 from 5 to 400 Torr was evaluated by
using a mathematical model based on the cross-sectional data of 10
anaesthetized monkeys. The CBF responses to alterations in
PaCO2 appear to have levelled off at low levels of
hypocapnia (i.e., <20 Torr) and hypercapnia (i.e., >60 Torr). However,
in the range of PaCO2 from 20 to 60 Torr, a range over
which measurements can be made in humans, the
CBF-PETCO2 relationship was described as a
straight line (27). In humans,
the data in the study by Hauge et al.
(9) showed that the
relationship between CBF (blood velocity in the internal carotid artery and
the vertebral artery) and PETCO2 was
described as linear in the range of PETCO2
from 25 to 55 Torr, and the CBF sensitivity to PaCO2
(CBF-PaCO2 sensitivity) leveled off only at low levels
of hypocapnia (i.e., <20 Torr). In the present study, judging by the
R2, both the one- and the two-linear regression models
were relatively poor models. This was not unexpected based on a previous
report of a slow adaptation in CBF in response to hypocapnia
(23). Fitting by a linear
regression assumes that there would be no change in
CBF-PETCO2 sensitivity. In this study, and on
the basis of the R2 value, the exponential model was the
best-fit model to describe the CBF-PETCO2
relationship in the range of PETCO2 from
20 to 50 Torr. This observation is supported by a study in humans
(15) and by studies in animals
(12,
35). In a study by Tominaga et
al. (34), it was shown that
the CBF responses in the range of PETCO2 from
20 to 50 Torr were described by two exponential models separating
the CBF responses between a hypocapnic-eucapnic region and a
eucapnic-hypercapnic region rather than by one exponential model.
CBF-PETCO2 sensitivity in hypocapnia. The response of CBF to alterations in PaCO2 is thought to be associated with a change in cerebral extracellular pH (18, 33). However, the exact mechanism by which extracellular pH might be involved in the process of cerebral vessels dilatation in response to PaCO2 remains unclear. In hypocapnia, a lower CBF-PETCO2 sensitivity might be associated with a metabolic adaptation associated with lactate acid formation in the brain (3). An increase in cerebral lactate production in response to respiratory alkalosis has been observed in humans (2). A facilitated lactate production may be caused by an increase in phosphofructokinase activity associated with an increase in pH (20), an excess uptake of glucose to O2 associated with cerebral tissue hypoxia caused by a reduction in CBF and/or associated with the Bohr effect (2). In rats it has been reported that cerebral tissue lactate progressively increases with decreases in PaCO2 in a hypocapnic environment, but cerebral tissue lactate does not appear to change with an increase in PaCO2 in a hypercapnic environment (16).
Effect of protocols on CBF-PETCO2 sensitivity. A statistical test of coincidence and parallelism indicated that the exponential regression models describing protocols I and D were not coincidental and not parallel. This implies that the CBF-PETCO2 sensitivity depends on which protocol is used. Not only is the CBF-PETCO2 sensitivity corresponding to protocol I higher than in protocol D, but the difference between the two is accentuated with increasing values of PETCO2 (as shown in Fig. 4). It is unlikely that an adaptation process can explain a difference between protocols. The duration of the PETCO2 steps was selected on the basis of the knowledge of time constants of CBF responses to alterations in PETCO2 (22) to ensure that the steps in both protocols were long enough for CBF to reach steady state yet short enough to avoid any influence of an adaptive process. However, previous studies have reported the presence of an undershoot and overshoot in CBF when PETCO2 is returned to prestimulus levels after 20 min of euoxic hypercapnia and euoxic hypocapnia, respectively (22). The difference in CBF-PETCO2 sensitivity between the protocols observed in this study is consistent with those findings. The mechanisms underlying these processes are unclear but may involve, at least in part, changes in the levels of lactate and bicarbonate (1, 5).
CBF-PETCO2 sensitivity at
altitude. The present study was conducted at a mild level of altitude
(i.e., 1,103 m above sea level). It has been reported that the
CBF-PETCO2 sensitivity is increased in an
acute exposure to moderate altitude
(13). In a recent study by
Poulin et al. (21), exposure
to hypoxia in a purpose-built chamber for 48 h, in which
PETO2 was held at 60 Torr, equivalent to
2,800 m (unacclimatized) and 3,400 m (acclimatized)
(25), increased
CBF-PETCO2 sensitivity by 28%. Likewise, a
5-day exposure to moderate altitude was reported to increase
CBF-PETCO2 sensitivity from 4%/Torr at sea
level to 5.2%/Torr (13),
although CBF-PETCO2 sensitivity was estimated
to remain unchanged after "correcting" for a lower cerebrospinal
fluid 
caused by hypocapnia. In the
present study, the CBF-PETCO2 sensitivity
calculated from the exponential model was estimated to be 5.3 and 4.8%/Torr at
55 Torr in protocols I and D, respectively. This observation
is comparable to the data obtained at sea level by Tominaga et al.
(34) in which a CBF
sensitivity of 6%/Torr was observed at a
PETCO2 of 55 Torr. Yet it is not clear
whether there is an effect of long-term exposure to mild altitude on the
CBF-PETCO2 sensitivity. This remains to be
investigated.
Technical considerations. A critical issue for the TCD technique
is the extent to which blood velocity reflects volume flow. Any changes in
diameter of the insonated artery will change blood velocity even when blood
flow is constant. In the study by Bishop et al.
(4), CBF responses determined
by 133Xe clearance technique were compared with changes in
p determined by TCD in
response to hypercapnia, and there was a good linear relationship between
these measurements. On the other hand, in the study by Clark et al.
(7), decreases in
p in response to
hypocapnia were relatively smaller compared with decreases in CBF determined
by 133Xe clearance technique, indicating that there may have been
dilatation of the MCA with hypocapnia. Poulin and colleagues
(22,
23) studied relative changes
in MCA diameter by using the Doppler power signal and demonstrated that MCA
diameter remained relatively constant at levels of hypocapnia
(23) or hypercapnia
(22) comparable to those
employed in this study. In support, in the study by Serrador et al.
(31), MCA diameter determined
by MRI was unchanged during hyperventilation, hypercapnia, and lower body
negative pressure.
Another important consideration is whether 2 min was long enough to obtain
steady-state CBF responses at each level of
PETCO2. This was assessed in a preliminary
study (unpublished observations) based on the previously reported values of
14–45 and 6–7 s for the on and off time constants for the MCA
blood flow response to step increases and decreases in
PETCO2
(22,
23), respectively. In two
subjects, we examined the responses of MCA velocity to several separate 5-min
step changes in PETCO2. With step increases
in PETCO2 of 2, 4, 6, 8, and 10 Torr, the
increases in p were 7, 20,
32, 39, and 46%, respectively, at 2 min and 7, 16, 26, 37, and 51% at 5 min,
respectively, suggesting that 2 min at each
PETCO2 step was long enough to allow
p to reach steady-state
values in the present study.
Changes in blood pressure with alterations in PaCO2 must also be considered. In healthy subjects, several studies have reported increases in mean arterial blood pressure (range of 6 to 13 mmHg; 7–14%) (15, 19, 26) and an increase in sympathetic nerve activity (19) with hypercapnia (PETCO2 range = 36–54 Torr). On the other hand, studies have shown little (6) or no change (14) in mean arterial blood pressure with hypocapnia. However, in the normal range of autoregulation (range of 60 to 150 mmHg), the CBF response to PaCO2 may be independent of changes in mean arterial blood pressure (10), but this has not yet been extensively studied. Because we did not specifically address the question of how changes in arterial blood pressure might affect differences in CBF-PETCO2 sensitivity in hypocapnia and hypercapnia or the differences in CBF-PETCO2 sensitivity between the protocols, we cannot exclude an effect of changes in blood pressure on the results reported in this study.
In summary, this study described the CBF-PCO2
relationship in the range of PETCO2 from
20 to 50 in humans. Over this range, a nonlinear exponential model
provided a reasonably good fit, suggesting that the
CBF-PETCO2 sensitivity is nonlinear and
varies depending on the level of PETCO2.
However, it was also shown that the CBF response to alterations in
PETCO2 was affected by the direction of the
stimulus. The mechanisms underlying these responses require further
investigation.
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ACKNOWLEDGMENTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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This study was supported by the Alberta Heritage Foundation for Medical Research (AHFMR), the Canadian Institutes of Health Research, and the Heart and Stroke Foundation of Alberta North West Territories and Nunavut. K. Ide was recipient of a Fellowship from the AHFMR.
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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REFERENCES |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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A. P. Binks, V. J. Cunningham, L. Adams, and R. B. Banzett Gray matter blood flow change is unevenly distributed during moderate isocapnic hypoxia in humans J Appl Physiol, January 1, 2008; 104(1): 212 - 217. [Abstract] [Full Text] [PDF]
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K. Peebles, L. Celi, K. McGrattan, C. Murrell, K. Thomas, and P. N. Ainslie Human cerebrovascular and ventilatory CO2 reactivity to end-tidal, arterial and internal jugular vein PCO2 J. Physiol., October 1, 2007; 584(1): 347 - 357. [Abstract] [Full Text] [PDF]
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J. A. H. R. Claassen, R. Zhang, Q. Fu, S. Witkowski, and B. D. Levine Transcranial Doppler estimation of cerebral blood flow and cerebrovascular conductance during modified rebreathing J Appl Physiol, March 1, 2007; 102(3): 870 - 877. [Abstract] [Full Text] [PDF]
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J. S. Vantanajal, J. C. Ashmead, T. J. Anderson, R. T. Hepple, and M. J. Poulin Differential sensitivities of cerebral and brachial blood flow to hypercapnia in humans J Appl Physiol, January 1, 2007; 102(1): 87 - 93. [Abstract] [Full Text] [PDF]
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J. M. Serrador, R. L. Hughson, J. M. Kowalchuk, R. L. Bondar, and A. W. Gelb Cerebral blood flow during orthostasis: role of arterial CO2 Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2006; 290(4): R1087 - R1093. [Abstract] [Full Text] [PDF]
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; incremental PETCO2) and D
(
; decremental PETCO2) for each
subject.