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J Appl Physiol 102: 87-93, 2007. First published October 5, 2006; doi:10.1152/japplphysiol.00772.2006
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Differential sensitivities of cerebral and brachial blood flow to hypercapnia in humans

Jimmy S. Vantanajal,1 Jon C. Ashmead,1 Todd J. Anderson,2,4 Russell T. Hepple,1,4,5 and Marc J. Poulin1,3,4,5

1Department of Physiology and Biophysics, 2Cardiac Sciences and Libin Cardiovascular Institute, and 3Department of Clinical Neurosciences, Faculties of 4Medicine and 5Kinesiology, University of Calgary, Calgary, Alberta, Canada

Submitted 13 July 2006 ; accepted in final form 27 September 2006


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Although it is known that the vasculatures of the brain and the forearm are sensitive to changes in arterial PCO2, previous investigations have not made direct comparisons of the sensitivities of cerebral blood flow (CBF) (middle cerebral artery blood velocity associated with maximum frequency of Doppler shift; VP) and brachial blood flow (BBF) to hypercapnia. We compared the sensitivities of VP and BBF to hypercapnia in humans. On the basis of the critical importance of the brain for the survival of the organism, we hypothesized that VP would be more sensitive than BBF to hypercapnia. Nine healthy males (30.1 ± 5.2 yr, mean ± SD) participated. Euoxic hypercapnia (end-tidal PO2 = 88 Torr, end-tidal PCO2 = 9 Torr above resting) was achieved by using the technique of dynamic end-tidal forcing. VP was measured by transcranial Doppler ultrasound as an index of CBF, whereas BBF was measured in the brachial artery by echo Doppler. VP and BBF were measured during two 60-min trials of hypercapnia, each trial separated by 60 min. Since no differences in the responses were found between trials, data from both trials were averaged to make comparisons between VP and BBF. During hypercapnia, VP and BBF increased by 34 ± 8 and 14 ± 8%, respectively. VP remained elevated throughout the hypercapnic period, but BBF returned to baseline levels by 60 min. The VP CO2 sensitivity was greater than BBF (4 ± 1 vs. 2 ± 1%/Torr; P < 0.05). Our findings confirm that VP has a greater sensitivity than BBF in response to hypercapnia and show an adaptive response of BBF that is not evident in VP.

cerebral blood flow; sensitivity to carbon dioxide

CEREBRAL BLOOD FLOW (CBF) is exquisitely sensitive to changes in the partial pressure of carbon dioxide in the arterial blood (PaCO2) (11). In humans, CBF increases by 3–5%/Torr PCO2 in the hypercapnic range (15, 31). PaCO2 is also a potent regulator of blood flow in the peripheral vasculature (2, 7, 21). In the brachial circulation, increases in blood flow of 10–30% during hypercapnia have been observed (18, 41). While several studies have examined the role of changes in PCO2 in either the cerebral or peripheral circulations, little has been done to assess the potential for differential sensitivity between these two vascular compartments in the same individual. The large variability of responses and protocols employed between previous investigations limits comparisons between the sensitivity of the vasculatures of the brain and forearm to CO2.

In 1932, Lennox and Gibbs (23) reported differences between the cerebral and femoral circulations of neurological patients in their responses to hypercapnia. Specifically, hypercapnia increased blood flow in the brain and decreased blood flow in the femoral circulation. Recent studies have not been consistent with these early findings, and there is now general agreement that hypercapnia elicits increases in both the cerebral and peripheral circulations (18, 31).

Despite results contradictory to more contemporary research, Lennox and Gibbs’s measurements in both cerebral and femoral circulations provided an initial opportunity to compare the regulation of central and peripheral vascular beds by PaCO2 in humans. More recently, Ainslie et al. (1) used simultaneous measurements of CBF velocity and femoral blood flow (FBF) to demonstrate not only that hypercapnia increased flow in both vascular beds but that the cerebrovascular response to hypercapnia was eightfold larger than the femoral response (5%/Torr vs. 0.6%/Torr, respectively). These results provide evidence of differential CO2 sensitivity between the cerebral and femoral circulations, but it remains unclear whether this phenomenon is consistent throughout other vascular beds of the peripheral circulation or whether there is further heterogeneity in CO2 sensitivity across different vascular beds.

Given that the maintenance of brain tissue oxygenation is critically important to the survival of the organism, it follows that the brain might respond with considerably more sensitivity to changes in PaCO2, as the concomitant change in pH poses a significant risk to cellular homeostasis. Furthermore, resting muscle has fairly low metabolic requirements, whereas neurons are among the most continuously metabolically active tissues. A highly sensitive regulatory mechanism may be essential to maintain sufficient blood flow to the brain during homeostatic perturbations. This study made simultaneous measurements of blood flow in the cerebral and brachial circulations and determined whether there are differences in CO2 sensitivity between these distinct vascular beds. We hypothesized that the sensitivity of CBF to hypercapnia would be greater than that in the forearm.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Nine healthy men (aged 30.1 ± 5.2 yr) volunteered to take part in this study. None of the subjects had a history of cardiovascular, cerebrovascular, or respiratory disease, and each volunteer received clearance from their family physician before participating. The study requirements were fully explained to each subject, and written informed consent was obtained before participating in the study. This study conformed to the standards set by the Declaration of Helsinki and was approved by the Conjoint Health Research Ethics Board at the University of Calgary (protocol ID# P15671 [GenBank] ).

Experimental Procedures

Each subject visited the laboratory on at least four occasions. The first visit was a familiarization session, while the second visit was used to ensure that satisfactory Doppler signals could be obtained from the middle cerebral and brachial arteries. The experimental protocols were carried out during the remaining two visits. Subjects were asked to refrain from consuming food and caffeine 4 h before each visit. At the beginning of each experiment the subject sat quietly and comfortably for 30 min. The first 20 min was used to set up the Doppler ultrasound probes for cerebral and brachial measurements. In the final 10 min, the subject’s resting end-tidal PCO2 (PETCO2) and end-tidal PO2 (PETO2) were measured by using a nasal cannula adapted from an oxygen therapy kit (Cannula-Adult w/2.1 M Oxygen Tube, Meridian Medical Systems, Indianapolis, IN). The respired gases were sampled continuously at a rate of 20 ml/min, and they were analyzed for fractional concentrations of O2 and CO2 by a mass spectrometer (AMIS 2000, Innovision, Odense, Denmark). The PETCO2 and PETO2 values were calculated and recorded on each breath using a computer and dedicated software (Chamber v1.00, University Laboratory of Physiology, Oxford, UK). These values were then averaged over the 10-min period and are referred to as resting PETCO2 and resting PETO2. These resting values were used to determine the desired end-tidal values for the protocol on that day.

Protocols

All protocols were 80 min in duration and consisted of a 10-min lead-in period, a 60-min intervention, and 10-min recovery period. PETO2 was held constant at 88 Torr (baseline for our altitude at the Univ. of Calgary, 1,103 m above sea level) for the duration of all protocols. During the lead-in and recovery periods, PETCO2 was held at 1.5 Torr above the subject’s resting level for that day (this is because dynamic end-tidal forcing can only add, not remove, CO2 from the inspirate; adding a small amount of CO2 makes it possible to regulate PETCO2 at the desired level). The 60-min intervention period depended on the randomly assigned protocol for that day. In protocol I (euoxic isocapnia), PETCO2 was held at 1.5 Torr above resting. During protocol II (euoxic hypercapnia), PETCO2 was increased rapidly (i.e., within 1 or 2 breaths) by 7.5 Torr (i.e., by 9.0 Torr above the subject’s resting value). Only one protocol was conducted on a given day, and this protocol was repeated twice on that day to improve the resolution of the measurements. The order of the protocols was randomized. On completion of the first trial of each day (intervention I), the subject was given a 1-h recovery period during which he was disconnected from the apparatus and breathed room air. After this period, the same protocol of the day was repeated (intervention II).

Experimental Techniques

Dynamic end-tidal forcing.   The control of the subject’s end-tidal gases was achieved by using the technique of dynamic end-tidal forcing and dedicated software (BreatheM v2.07, University Laboratory of Physiology, Oxford, UK). This system allows for the accurate control of end-tidal gases on a breath-by-breath basis despite variations in a subject’s ventilatory rate (15, 35). On the basis of the desired PETCO2 and PETO2, a controlling computer generated inspired partial pressures of each gas predicted to achieve the desired values, using an integral proportional feedback algorithm (35, 36).

Transcranial Doppler ultrasound.   A 2-MHz pulsed transcranial Doppler ultrasound system (TC22, SciMed, Bristol, UK) was used to measure the velocity of blood flowing through the middle cerebral artery (MCA) as an index of CBF. The Doppler probe was positioned to allow for the measurement of backscattered Doppler signals from the right MCA. The MCA was identified by an insonation pathway through the right temporal window just above the zygomatic arch (33). After applying ultrasound gel (Aquasonic 100, Parker Laboratories, Fairfield, NJ) to the probe, the angle and position of the probe and sample depth were adjusted to obtain the signal with maximum power and optimal quality of the Doppler spectra. Once the optimal signal was achieved, ultrasound gel was reapplied, and the probe was securely positioned in a headband device (Müller and Moll Fixation, Nicolet Instruments, Madison, WI) to maintain the optimal insonation position and angle throughout the experiment.

Signals from the maximum Doppler frequency shifts were measured and updated each time a new spectrum was calculated every 10 ms. The maximum frequency shift of the Doppler spectra provided the peak blood velocity (VP) (33). In this study, VP was averaged over each heart beat (VP), and this was used as the primary index of CBF. The power signal (P), which provided an index of relative changes in cross-sectional area of the MCA, was also recorded (33). The signals for VP and P were available as analog signals and were saved on the acquisition computer for later analysis.

BBF and vascular imaging.   Determination of blood flow through the brachial artery (as an estimate of forearm blood flow) was achieved with Doppler ultrasound imaging. The subject’s right arm was extended laterally and comfortably stabilized within a sling, which was suspended from a retort stand apparatus. The apparatus was, in turn, secured to a small table via adjustable c-clamps. Identification of the imaging site was first estimated by palpating the brachial pulse, approximately 8–10 cm proximal to the right epicondyle. A 7.5-MHz linear array ultrasound transducer (Hewlett-Packard, Andover, MA) was used to obtain a clear longitudinal image of the brachial artery. This two-dimensional (2D) image was then visually examined to identify the segment with the clearest anterior and posterior intimal surfaces along the vessel wall. This segment was magnified using a zoom feature on the ultrasound imaging system and selected for continuous 2D gray-scale imaging. The probe position was secured via an adjustable three-claw clamp attachment, which was secured to the retort stand apparatus.

Blood velocity measurements were obtained using spectral pulsed-wave Doppler ultrasonography (Sonos 1000, Hewlett-Packard). The sampling gate encompassed the interior lumen diameter of the brachial artery. Blood velocity measurements were performed during the last 40 s of each minute, with the probe in the lowest insonation angle possible and always below 60° (8). Brachial artery diameter measurements were made during the first 20 s of each minute. During online analysis, the envelope trace of 9–12 consecutive waveforms, during the last 40 s of each minute, was used to determine the average velocity time integral (VTI) for that minute. Blood flow was then calculated as:

Formula
where BBF is in milliliters per minute, VTI is in centimeters per beat, HR is heart rate (beats/min), and VD is vessel diameter (cm).

Normalization and comparisons.   VP and BBF were normalized to the last 5 min of the lead-in period to allow for comparisons between the blood flow responses for each vascular bed.

Blood flow sensitivity to CO2.   CBF sensitivity to hypercapnia was assessed by fitting a dynamic single-compartment model to the VP data (31). The model included seven parameters, namely, gain terms for the on- and off-transients (Gon and Goff); time constants for the on- and off-transients ({tau}on, {tau}off); baseline terms for the on- and off-transients [(VP)on, (VP)off]; and a single pure time delay (Td).

Individual estimates of BBF sensitivity (or gain) were calculated manually for interventions I and II of hypercapnia. Two separate gain terms were determined. The first gain term (gain 1) was determined during the steady-state period following the onset of the stimulus. The second gain term (gain 2) was determined immediately before the relief of the stimulus. We assumed that the change in BBF from resting steady state is proportional to the change in PETCO2. Therefore, the gain term G for hypercapnia was calculated using the following equation:

Formula
where G is in milliliters per minute per Torr, {Delta}BBF is the change in BBF (ml/min) relative to the resting steady-state value, and {Delta}PETCO2 is the change in PETCO2 (Torr) relative to the resting steady-state value.

Values for BBF and PETCO2, during minutes 2–6, were used to determine gain 1 (Gb1) since the BBF response had reached a steady state by 2 min. Gain 2 (Gb2) was determined from values corresponding with minutes 56–60.

Other Measurements

Blood pressure was measured continuously and noninvasively by using photoplethysmography (Portapres, TNO TPD Biomedical Instrumentation, Amsterdam, The Netherlands) of the left ring finger. Since this measurement took place below the level of the heart, a hydrostatic height correction was performed. This involved placing a height correction transducer at the level of the heart following a height nulling procedure. Mean arterial pressure (MAP) was calculated by the offline analysis software. Arterial oxygen saturation (%, SpO2) was measured on the left index finger by using a pulse oximeter (model 3900p, Datex-Ohmeda, Madison, WI). HR was monitored continuously using a three-lead ECG configuration (Micromon 7142 B, Kontron Medical, Milton Keynes, UK). Three additional leads, connected to the Doppler ultrasound system, were placed alongside the three original leads, in the same configuration. This signal was needed to standardize VD measurements in the brachial artery to ensure each was taken at end diastole.

Statistical Analysis

Results are reported as means ± SD. Several comparisons were performed using a variety of statistical procedures (Sigmastat 3.0, SPSS, Chicago, IL). Tukey’s honestly significantly different post hoc analysis was used where appropriate (i.e., ANOVAs). Statistical significance was set a priori at P ≤ 0.05.

Paired t-tests were used to examine differences in baseline PETO2, PETCO2, HR, MAP, and BBF between interventions I and II for each experimental protocol. An average of the last 5 min of values during the baseline period, immediately preceding the onset of the intervention stimuli (i.e., hypercapnia), was used for comparison between interventions I and II. Paired t-tests were also used to assess differences between interventions I and II for BBF sensitivity and model parameters of the VP response. The BBF gains (Gb1 and Gb2) were also compared in this manner.

One-way ANOVA analysis was used to compare baseline PETO2, PETCO2, HR, MAP, VP, and BBF between each experimental day. Coefficients of variation between experimental days were calculated for baseline variables. One-way repeated-measures ANOVA (1-min averages) was performed to confirm the time at which BBF had reached a "steady-state" response after the onset of the intervention stimuli. This information was used to determine the time interval for calculating BBF sensitivity.

Comparisons between interventions I and II for the input stimuli (2-way ANOVA), as well as the blood flow sensitivities, showed no significant differences [1-way ANOVA; coefficients of variation for baseline blood flow values between experiments were small (CBF = 6.7%; BBF = 15.0%)]. Therefore, minute-by-minute values of HR, MAP, VP, and BBF were averaged together for interventions I and II.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
The average age, height, weight, body mass index, and resting PETCO2 and PETO2 of the subjects (n = 9) were 30.1 ± 5.2 yr, 179.2 ± 7.4 cm, 78.7 ± 8.2 kg, 24.5 ± 2.3 kg/m2, and 37.8 ± 1.8 and 87.0 ± 2.2 Torr, respectively. On a few occasions, subjects were not able to complete two interventions in one session (i.e., minor subject discomfort). Therefore, these sessions were repeated with additional visits.

Pattern of Responses

Both VP and BBF are expressed as a percentage of a 5-min baseline immediately preceding time 0. The results from the control experiments (Fig. 1A) demonstrate the control of end-tidal gases during the experiment as well the relatively stable blood flow responses under euoxic isocapnia conditions. During euoxic hypercapnia (Fig. 1B), both VP and BBF increased (33.8 ± 8.4 and 13.7 ± 8.3%, respectively). There was a gradual decline in BBF during the 60 min of hypercapnia, reaching 1.6 ± 15.6% above baseline by the end of the step. This value was not different from baseline. The adaptive process observed in BBF was not present in the corresponding VP measurement. A small decrease in VP (1.4 cm/s) occurred during the control protocol (P < 0.05; Table 1). There was no change in HR during the control protocol, but a 11% increase was observed during hypercapnia (P < 0.05). MAP was also elevated above baseline by the end of the control and hypercapnic protocols (P < 0.05; Table 1).


Figure 1
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  		Fig. 1. Group average (interventions I and II) of time-related changes in end-tidal PCO2 (PETCO2), end-tidal PO2 (PETO2), normalized velocity associated with maximum frequency of the Doppler shift (VP), and normalized brachial blood flow (BBF). A: euoxic isocapnia. B: euoxic hypercapnia. Each symbol represents a 60-s mean ± SD; n = 9 subjects, 2 repetitions per subject, 18 responses. Normalized values are expressed as percentage of average value for 5-min period preceding time 0.

 

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  		Table 1. Responses during the control, hypocapnic, and hypercapnic protocols

 
Modeling of VP Responses

The breath-by-breath average of the input stimulus (i.e., PETCO2), along with the beat-by-beat average for VP during the hypercapnic protocol, is illustrated in Fig. 2. Also illustrated are the average model fit and residuals for the responses. The data from subject 76 were excluded from these group averages because of technical difficulties. Generally, the model fits of the data are good, although slight imperfections can be noted during the experiments, especially during the on- and off-steps. The parameters obtained from the modeling procedure for all subjects, along with the calculated sensitivities for BBF, are summarized in Table 2.


Figure 2
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  		Fig. 2. Group averages (n = 8) of the VP responses (bullet), model fit (gray line), and residuals. Data represent ensemble averages of data from both interventions I and II for 8 subjects. Beat-by-beat data are interpolated over 0.5-s intervals.

 

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  		Table 2. Estimated model parameters for brachial and cerebral blood flow responses to hypercapnia

 
Comparison of Sensitivities between VP and BBF

The sensitivity of the VP response to hypercapnia was found to be greater than the sensitivity of the BBF response to hypercapnia (4.3 ± 1.2 vs. 1.9 ± 1.1%/Torr, P < 0.05). A second gain for BBF was calculated at the end of hypercapnia due to the gradual decrease in BBF during the protocol. The sensitivity of BBF to CO2 determined at that point was found to be lower than the gain calculated at the beginning of the hypercapnic period (1.9 ± 1.1 vs. 0.3 ± 2.1%/Torr, P < 0.05).

Intervention I vs. Intervention II

The gains for BBF did not vary between interventions I and II for hypercapnia. Comparisons made with the estimated model parameters for the VP response to hypercapnia revealed a significantly lower recovery (VP)R during intervention II (P < 0.05). All other model parameters did not vary between interventions.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
This study made simultaneous measurements of the MCA VP and BBF responses to alterations in PETCO2 over 60 min and compared their sensitivities. Our findings demonstrate that the vasculature of the brain is more sensitive to elevations in PETCO2 than the vasculature of the forearm. Furthermore, our results demonstrate that BBF adapts to hypercapnia, such that BBF is no longer elevated after 60 min. Adaptive responses were not observed for VP.

Overall changes in blood flow occurred in the same direction for both vascular beds. The changes in VP were similar to those reported previously for hypercapnia (32), although these prior studies used shorter observation periods (e.g., 2–20 min). BBF responses were also similar to previous investigations involving hypercapnia (18–20). As with CBF, observation periods for BBF in these prior studies were also considerably shorter than the current study (e.g., <10 min).

Differential Sensitivities Between the Brain and Forearm

Increased sympathetic nerve activity (SNA) associated with hypercapnia (3, 14, 40), along with differential autonomic regulation of cerebral and brachial vascular beds, may generate, at least in part, the observed differences in sensitivity. The physiological significance of sympathetic innervation of cerebral vessels is an area of debate. There is evidence that SNA increases cerebrovascular resistance, reduces blood flow, and attenuates the CBF response to hypercapnia (17, 42). However, SNA has also been shown to have no effect on the cerebrovascular responses to CO2 (9, 22, 34). In contrast, a more defined role of SNA may be present in the periphery. During mild hypercapnia (5% inspired CO2), {alpha}-adrenergic receptor-mediated vasoconstriction and reduced blood flow have been observed (16). During more severe hypercapnia (8–30% inspired CO2), vasodilation is observed, suggesting that other regulatory mechanisms are able to override sympathetic vasoconstriction (2). Ainslie et al. (1) demonstrated that handgrip-induced sympathetic activation did not alter CBF but decreased FBF. They also showed that the increase of CBF in response to hypercapnia was much greater than that of FBF (5%/Torr vs. 0.6%/Torr). Thus it appears that peripheral vessels may be under greater influence from sympathetic activity. This is supported anatomically by a greater distribution of {alpha}-adrenoreceptors in the peripheral vascular beds relative to the cerebral vessels (1, 4). Such a mechanism would be important in preventing profound vasodilatation during skeletal muscle activation, allowing for blood pressure to be maintained, as well as diverting blood to essential organs such as the brain (1, 37).

Differential sensitivity between the vessels of the brain and forearm could result, in part, from sustained pressure differences between them as a result of upright posture (6, 27, 29, 30). Newcomer et al. (27) reported blunted vascular responses to both endothelium-dependent and -independent vasodilator agents in the leg compared with the forearm and suggested a role for differences in blood pressure within those beds. Pawelczyk and Levine (30) also suggested that chronic exposure of the legs to greater pressures could be associated with functional or morphological differences between the leg and arm. In the brain, cerebrovascular reactivity has been shown to decline in response to elevated pressures as seen in chronic hypertension (5, 24, 39). Furthermore, the elevation of blood pressure in the cerebral vasculature of rats subjected to hindlimb unloading has been shown to enhance basal tone and vasoconstriction in basilar artery and MCA (44, 47).

Differences in the endothelium and smooth muscle of each vascular bed may also be of some significance since vasodilatory mediators like nitric oxide and prostacyclin (PGI2) are important in generating responses to hypercapnia (10, 28). However, since phenotypic differences between endothelial and smooth muscle cells can also be found within branches of the same vascular bed, other mechanisms are likely to play a greater role (12, 27).

Adaptive Responses to Hypercapnia

The CBF response during 60 min of hypercapnia was characterized by a sustained increase, with no significant decline over time. Results from lamb, dog, and sheep models using prolonged interventions (6–96 h) suggest that CBF does decline toward baseline during sustained hypercapnia (13, 43, 46). Results from the present study suggest that 1-h exposures to mild hypercapnia are not associated with an adaptive process. Unlike the brain, blood flow in the arm gradually declined in this study, such that it was not significantly different relative to baseline by the end of the protocol. Previous studies have had limited observation periods (e.g., <10 min) and may have precluded the detection of any adaptive responses (19, 20, 25).

The fact that BBF returned to baseline over time while CBF did not further suggests differences in their regulatory mechanisms in response to PaCO2. The influence of sympathetic outflow to these vascular beds is not equivalent. One possibility is that the vasoconstrictor effects from sympathetic activity were able to override, over time, the local vasodilatory effects of increased PaCO2. During 30 min of hypercapnia, sympathetic outflow is consistently elevated above baseline, with no indication of decline (26, 45). This evidence suggests that a decline in sympathetic nerve activity during our study is unlikely and, therefore, the vasoconstrictor stimulus persists throughout the protocol. To shift the balance toward vasoconstriction (i.e., adaptation), there must be a decline in the vasodilatory stimuli. How this is mediated is unclear. Furthermore, the mechanisms that underlie the ability of the brain to maintain elevated blood flow during hypercapnia are also unknown. The fact that the brain is more metabolically active than the resting muscle of the forearm in our study may have contributed to the sustained increase in CBF.

Limitations

There were several limitations associated with this investigation. First, transcranial Doppler was used to measure blood flow velocity through the MCA rather than blood flow. Therefore, only relative changes in blood flow between the brain and arm could be compared. As pointed out by Newcomer et al. (27), this could lead to errors in the magnitude of the responses if there were errors in our baseline measurements. However, the coefficients of variation for our baseline blood flow values between experiments were small (CBF = 6.7%; BBF = 15.0%), showing that we were able to consistently establish resting baseline values, which would limit the error in the magnitude of the responses.

Another limitation with transcranial Doppler is the diameter of the insonated vessel (i.e., MCA) is assumed to remain constant, thus allowing changes in velocity to reflect changes in downstream resistance and blood flow. However, this assumption has been validated previously by using the total power of the Doppler spectrum as an index of relative changes in cross-sectional area (33), as well as through more direct observations using magnetic resonance imaging (38).

Third, the temporal resolution of the echo Doppler was not sufficient to allow for an assessment of the dynamic aspects of the BBF response. Since transcranial Doppler permitted beat-by-beat measurements of VP, we were able to apply simple mathematical models to the data to determine gains, time constants, and time delays for the response. Comparisons of BBF and CBF regarding these aspects would further improve our understanding of how these distinct vascular beds respond to PaCO2.

Finally, the present study demonstrates that 1) CBF is more sensitive than BBF to hypercapnia and 2) BBF adapts to 60 min of hypercapnia while CBF remains elevated throughout. Further studies are necessary to elucidate the mechanisms underlying the differential sensitivity of these vascular beds.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
ACKNOWLEDGMENTS
 REFERENCES
 
This project was supported by the Alberta Heritage Foundation for Medical Research (AHFMR); Heart and Stroke Foundation of Alberta, NWT, and Nunavut; the Canadian Institutes of Health Research; and the Canada Foundation for Innovation (New Opportunities Fund to M. J. Poulin). J. S. Vantanajal was supported by an Alberta Lung Association Studentship and University of Calgary Graduate Scholarship. T. J. Anderson and M. J. Poulin are AHFMR Senior Medical Scholars.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
REFERENCES
 
We gratefully acknowledge Dr. P. A. Robbins for assistance in setting up the dynamic end-tidal forcing technique in Calgary. We also thank Dr. K. Ide for technical support and feedback on the manuscript.


   FOOTNOTES
 

Address for reprint requests and other correspondence: M. J. Poulin, Dept. of Physiology and Biophysics, Faculty of Medicine, Univ. of Calgary, Calgary, Alberta, T2N 4N1 Canada (e-mail: poulin{at}ucalgary.ca)

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.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 

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