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Ann Thorac Surg 2004;77:1664-1670
© 2004 The Society of Thoracic Surgeons

Original article: cardiovascular

Use of a pH-stat strategy during retrograde cerebral perfusion improves cerebral perfusion and tissue oxygenation

Jian Ye, MDa,b,d*, Zhijun Li, MDb, Yanmin Yang, MDb, Luojia Yang, MDc, Allan Turnerd, Michael Jackson, PhDd, Roxanne Deslauriers, PhDd

a Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada
b Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada
c Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada
d Institute for Biodiagnostics, National Research Council of Canada, Winnipeg, Manitoba, Canada

Accepted for publication October 2, 2003.

* Address reprint requests to Dr Ye, Biosystems, Institute for Biodiagnostics/NRC, 435 Ellice Ave, Winnipeg, ManitobaR3B 1Y6, Canada
e-mail: jian.ye{at}nrc-cnrc.gc.ca


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: Although it is well documented that the use of a pH-stat strategy during hypothermic cardiopulmonary bypass improves cerebral blood flow, an {alpha}-stat strategy has been almost exclusively used during retrograde cerebral perfusion. We investigated the effects of pH-stat and {alpha}-stat management on brain tissue blood flow and oxygenation during retrograde cerebral perfusion in a porcine model to determine if the use of a pH-stat strategy during retrograde cerebral perfusion improves brain tissue perfusion.

METHODS: Fourteen pigs were managed by an {alpha}-stat strategy (alpha-stat group, n = 7) or by a pH-stat strategy (pH-stat group, n = 7) during 120 minutes of hypothermic retrograde cerebral perfusion. Retrograde cerebral perfusion was established through the superior vena cava. Brain tissue blood flow and oxygenation were measured continuously with a laser flowmeter and near infrared spectroscopy, respectively. Brain tissue water content was determined at the end of the experiments.

RESULTS: During cooling, brain tissue blood flow was significantly higher with use of the pH-stat strategy than with the {alpha}-stat strategy (86% ± 10% versus 40% ± 3% of baseline). During retrograde cerebral perfusion, brain tissue blood flow was also significantly higher (about three times higher) in the pH-stat group than in the alpha-stat group (15% ± 4% versus 5% ± 1% of baseline at 60 minutes of retrograde cerebral perfusion). Tissue oxygen saturation appeared to be higher during retrograde cerebral perfusion in the pH-stat group than in the alpha-stat group. Brain tissue blood flow during rewarming remained significantly higher with the use of pH-stat than with the use of {alpha}-stat. Brain tissue water contents were similar in both groups.

CONCLUSIONS: In our pig model, the use of a pH-stat strategy during retrograde cerebral perfusion significantly improves brain tissue perfusion. Therefore, to improve retrograde cerebral blood flow during retrograde cerebral perfusion, it may be preferable to use a pH-stat strategy, rather than an {alpha}-stat strategy.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 References
 
The management of pH during cardiopulmonary bypass (CPB) has been explored extensively but still remains controversial. Two strategies, {alpha}-stat and pH-stat, are currently used to manage blood acid-base balance during hypothermic CPB. Although {alpha}-stat blood gas management during hypothermic CPB is widely used, particularly in adult cardiac patients, pH-stat management is more physiologic [1] and used more commonly in children. The advantages of pH-stat management during hypothermic CPB include increased cerebral blood flow resulting from cerebral vasodilation secondary to high carbon dioxide, and a decrease in the hypothermia-induced left shift of the oxyhemoglobin dissociation curve [2, 3]. These changes would result in an increase in oxygen supply and availability to brain tissue. In contrast, the major argument for using {alpha}-stat management during hypothermic CPB has been to avoid pH-stat-induced "luxury perfusion" and consequent increase in likelihood of microembolization, as well as to maintain optimal intracellular enzyme function [4, 5].

Although both {alpha}-stat and pH-stat strategies have been used during hypothermic CPB, only the {alpha}-stat strategy appears to be used for pH management during hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion (RCP). Clinical and experimental studies have indicated that RCP provides better brain protection relative to HCA alone. However, the major drawback of RCP is that it does not provide sufficient blood flow to brain tissue [6–8]. Because the pH-stat strategy results in vasodilation, reduces vascular resistance, and leads to an increase in cerebral blood flow, we hypothesized that the use of a pH-stat strategy during hypothermic RCP would increase brain tissue blood flow during RCP.

In the present study, the combination of laser Doppler flowmetry and near infrared (NIR) spectroscopy was used to follow changes in regional brain tissue blood flow and oxygenation in real time [9, 10] to determine the effects of pH-stat strategy during RCP on brain tissue perfusion and oxygenation.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 References
 
Fourteen pigs aged less than 5 months (weighing 40 to 60 kg) were used after a minimum of 12 days acclimation in the animal facility of the Institute for Biodiagnostics. All pigs were fasted with access to water for 12 hours before surgery. All animals received humane care in compliance with the guidelines of the Canadian Council on Animal Care.

Surgical preparation
As described previously [7, 8, 11], preanesthesia was induced with midazolam (0.3 mg · g-1, IM), ketamine (20 mg · g-1, IM), and atropine (0.02 mg · g-1, IM). Muscle relaxation was obtained with pancuronium 0.1 mg · g-1. After endotracheal intubation, the pig was ventilated mechanically with 60% oxygen and 40% air. The ventilator rate and tidal volume were adjusted to maintain arterial CO2 tension between 35 and 45 mm Hg at normal temperature. Anesthesia was maintained with 1.5% to 2.0% isoflurane. Urine was collected through a bladder catheter. A temperature probe was placed in the esophagus. Because direct monitoring of brain temperature is not practical and not used clinically, esophageal temperature was used to monitor body core temperature.

The right temporal muscle was exposed, retracted, and partially excised. Two small holes (0.4 cm and 0.2 cm diameter) were made in the skull bone using a burr drill. The dura was exposed and remained intact. The holes were prepared for placement of NIR spectroscopy and laser flowmeter probes.

A median sternotomy was used to expose the heart. A small catheter was placed in the brachiocephalic artery through the right internal mammary artery to measure blood pressure and obtain venous blood samples during RCP. Another small catheter was placed, through the left internal mammary vein, into the right internal jugular vein beyond a venous valve to measure perfusion pressure during RCP and for blood sampling. After 500 IU/kg heparin, the cardiopulmonary bypass (CPB) circuit was set up with cannulation of the ascending aorta (22F cannula) and the right atrium (28F single-stage venous cannula). The superior vena cava (SVC) was cannulated with a modified two-lumen cannula. The large lumen (2-mm internal diameter) was used for RCP through the SVC and the small lumen was used to monitor central venous pressure. The lungs were not inflated during CPB or circulatory arrest.

The CPB circuit consisted of Cobe roller pumps (model c22.2, Cobe, Arrada, CO), cardiotomy reservoir (Cobe HVRF 3700), arterial filter (40 micron, dideco D733, Mirandola, Italy), water bath (Lauda MGW type RMSG, Postfach, Germany), and membrane oxygenator (Cobe Optima) with integrated heat exchanger. The system was primed with 1,000 mL lactated Ringer's solution, 500 mL Pentaspan, 25 mL of 1 mole/L sodium bicarbonate, and 5,000 IU heparin. The CPB circuit was designed to allow switching between RCP and CPB.

Experimental groups and protocol
Fourteen pigs were randomly assigned to one of the following two groups: alpha group (n = 7), using an {alpha}-stat strategy for acid-base management during cooling, profound HCA with RCP and rewarming; and pH group (n = 7), using a pH-stat strategy for acid-base management during cooling, profound HCA with RCP, and rewarming. The experimental protocol is shown in Table 1.


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  		Table 1. Experimental Protocol

 
After setting up equipment for NIR spectroscopy and the laser flowmetry (see below), normothermic CPB (37°C) was initiated and continued for 15 to 20 minutes to allow stabilization of body temperature and blood gases. After obtaining baseline values for all variables, the pig was gradually cooled from 37°C to 15°C with a temperature gradient of less than 10°C between the water bath and blood, which took 30 to 40 minutes. Circulatory arrest was achieved when the esophageal temperature reached 15°C. Retrograde cerebral perfusion was performed for 120 minutes through the catheter in the SVC, which was snared. During RCP, deoxygenated blood returned to the cardiotomy reservoir through the aortic cannula and gravity drainage of the inferior vena cava (IVC), which was not snared. The azygos vein remained patent. The RCP perfusion pressure measured in the internal jugular vein was continuously monitored and carefully controlled at 35 to 40 mm Hg. At the end of circulatory arrest, CPB was resumed and the pig was gradually rewarmed to 37°C with a temperature gradient of less than 10°C between the water bath and blood. Normothermic CPB was continued for an additional 60 minutes. No inotropic drugs were used during the experiments. Immediately after each experiment, the brain was removed for measurement of brain tissue water content and histopathology.

In this study, the IVC was not clamped and the azygos vein was not snared during RCP at the relatively high pressures of 35 to 40 mm Hg because our previous study in the same animal model demonstrated that RCP under these conditions led to better brain tissue perfusion relative to RCP with a clamped IVC and azygos vein, and did not cause brain edema [11]. Our recent studies further confirm that clamping the IVC and azygos vein during RCP results in critically high intracranial pressures and brain edema even at retrograde perfusion pressures of 25 to 30 mm Hg (submitted for publication).

Measurements
Laser flowmetry and NIR were used to monitor brain tissue blood flow and tissue oxygenation (oxyhemoglobin and deoxyhemoglobin) in a continuous manner [11]. Brain oxygen extraction and water content of brain tissue were also determined.

Cerebral cortical blood flow
The theory and use of laser flowmetry has been described in detail elsewhere [9] and used successfully in our pig model [11]. Regional cerebral blood flow (rCBF) was continuously monitored using a BLF 21D (Advance Company, Tokyo, Japan) laser Doppler flowmetry fitted with a needle-type probe (Type Nspi:9051U) mounted on a home-made holder. The probe was carefully advanced to touch the dura without visibly indenting the dura. Areas with visible large blood vessels were avoided. The data were recorded in absolute blood flow units (mL · 100 g–1 · min–1) once the reading was stable.

Cortical tissue oxygenation
Cerebral oxygenation was monitored using NIR spectroscopy. Near infrared spectra were acquired using a Foss Analytical NIR Systems 6500 NIR spectrometer (Foss Analytical, Silver Springs, MD) equipped with a randomized bifurcated fiber optic bundle. The end of the fiber optic probe was positioned on the cerebral temporal cortex of the right side of the brain through a small hole (0.4 cm diameter) in the skull and held in place with sutures and a home-made holder. An area without any major visible vessels was used for acquisition of the NIR spectra. For each measurement, 32 scans were acquired and summed to produce spectra. Three baseline spectra were acquired during normothermic CPB, with spectra acquired every 5 minutes during the remainder of the experimental protocol [11].

Brain oxygen extraction
Arterial and venous blood samples were obtained simultaneously at each stage of the protocol to monitor blood gases, pH, and electrolytes. Venous or deoxygenated blood samples were collected from the right internal jugular vein and common carotid artery during CPB and RCP, respectively. Blood gases were measured immediately after sample collection using a blood gas analyzer (Stat 9, NOVA Biomedical, Waltham, MA). An {alpha}-stat strategy (measured values were not temperature-corrected to the pig's actual body temperature) or pH-stat strategy (measured values were temperature-corrected to the pig's actual body temperature) was used to manage blood pH. Oxygen content was calculated based on the formula: O2 content (vol %) = [HB] x 1.36 x SO2 + PO2 x 0.003 (HB = hemoglobin concentration, SO2 = oxygen saturation). Oxygen extraction was calculated using the formula: oxygen extraction (%) = (inflow O2 content – outflow O2 content)/inflow O2 content x 100% [11].

Brain tissue water content
Blocks of tissue from different regions in the brains were obtained and weighed. After weighing, the tissue was dried at 60°C and weighed daily until a constant weight was obtained (typically 72 hours). Tissue water content (%) = (wet weight – dry weight)/(wet weight) x 100% [11].

Histopathologic exa mination
The experimental details of the histopathological studies are described in a previous publication [12]. At the end of each experiment, the brain was removed and fixed with formaldehyde solution. Tissue samples obtained from seven different regions were cut into 5-mm slices, which were stained with hematoxylin and eosin. Injury was graded (0 to 5) on the basis of the number of damaged neurons within each region, as follows: grade 0, normal; grade 1, less than 10%; grade 2, 10 to 25%; grade 3, 26 to 50%; grade 4, 51 to 75%; and grade 5, more than 75%.

Statistical analysis
Mean cerebral blood flow, oxyhemoglobin, and deoxyhemoglobin signals obtained during initial normothermic CPB were used as baseline levels and set at 100%. Statistical analysis was performed using the Statistical Analysis System (SAS Institute, Cary, NC). All data are presented as mean ± standard error of the mean. A repeated-measures analysis of variance (ANOVA) and Duncan's multiple range test were used for comparison between different time points within a group, and Student's t test was used for comparison between the two groups. A p value less than 0.05 was considered significant.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 References
 
Pump/Retrograde flow during RCP
As shown in Figure 1, the mean pump flow during normal CPB was 79.8 to 80.4 mL · kg–1 · min–1 in both groups. During RCP, the pump/retrograde flow was 13.5 to 14.9 mL · kg–1 · min–1 in the alpha group and 12.4 to 16.0 mL · kg–1 · min–1 in the pH group to achieve internal jugular vein pressures of 35 to 40 mm Hg. There was no significant statistical difference between the two groups in the pump/retrograde flow during RCP. During the rewarming period, with controlled blood pressure, the pump flow quickly returned to the baseline level and remained higher than baseline in the pH group, while the recovery of pump flow was slow in the alpha group. The difference reached statistical significance between the two groups during rewarming from 15°C to 25°C.



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  		Fig 1. Pump flow during experiments in the {alpha}-stat (triangles) and pH-stat (squares) groups. *p less than 0.05 versus the alpha group. (CPB = cardiopulmonary bypass; CPB-b = baseline levels obtained during initial CPB; RCP = retrograde cerebral perfusion; Temp. = temperature.)

 
Regional cerebral blood flow
Regional cerebral blood flow was measured continuously throughout the experimental protocol. The mean value obtained during initial normothermic CPB was used as the baseline (100%). In the alpha group, rCBF decreased sharply during cooling and reached 39.8% ± 3.3% of the baseline level at 15°C, which is consistent with our previous findings [11]. In contrast, the decline of rCBF was very limited during cooling from 37°C to 15°C in the pH group and remained 85.6% ± 10.1% of the baseline level at 15°C. During RCP, rCBF was significantly higher in the pH group (13.5% to 18.1% of baseline level) than in the alpha group (4.8% to 6.2% of baseline level). During rewarming, the increase in rCBF was more rapid and rCBF remained higher with use of the pH-stat strategy than with the {alpha}-stat strategy (Fig 2).



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  		Fig 2. Change in brain tissue blood flow determined by laser flowmetry during retrograde cerebral perfusion (RCP) with the use of the pH-stat strategy (pH group = squares) and the {alpha}-stat strategy (alpha group = triangles). The levels obtained during initial normothermic cardiopulmonary bypass (CPB) were used as baseline (100%). *p less than 0.05 versus the alpha group. (CPB-b = CPB baseline; Temp. = temperature.)

 
Tissue oxygenation
From the NIR spectra, the peak areas of deoxyhemoglobin and oxyhemoglobin were quantitated using a computer program [13, 14]. Oxyhemoglobin and deoxyhemoglobin were expressed as the ratio of oxyhemoglobin/total hemoglobin and deoxyhemoglobin/total hemoglobin. The level obtained during initial normothermic CPB was used as the baseline level (100%). A gradual increase in oxyhemoglobin level and a decrease in deoxyhemoglobin were observed during cooling in both groups and the changes were more significant in the pH group than in the alpha group (Fig 3, A and B). During RCP in both groups, the oxyhemoglobin levels were lower and deoxyhemoglobin higher than their baseline levels, but the oxyhemoglobin level was significantly higher and the deoxyhemoglobin level appeared to be lower in the pH group than in the alpha group. More interesting was that the oxyhemoglobin and deoxyhemoglobin levels returned to their baseline levels very rapidly during rewarming in the pH group, whereas in the alpha group, these levels did not return to baseline until 45 minutes after complete rewarming (Fig 3, A and B).



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  		Fig 3. (A) Changes in brain tissue oxyhemoglobin and (B) deoxyhemoglobin, as well as (C) brain tissue oxygen saturation determined by near infrared spectroscopy during experiments in the {alpha}-stat (triangles) and pH-stat (squares) groups. In the upper and middle panels, the levels obtained during initial normothermic cardiopulmonary bypass (CPB) were used as baselines (CPB-b, 100%). *p less than 0.05 versus the alpha group. (RCP = retrograde cerebral perfusion; Temp. = temperature.)

 
Tissue oxygen saturation during initial normothermic CPB was similar in both groups (87.2% ± 2.8% in the alpha group versus 88.5% ± 2.3% in the pH group). During cooling, tissue oxygen saturation increased more significantly in the pH group than in the alpha group. Tissue oxygen saturation decreased during RCP in both groups. However, tissue oxygen saturation was higher throughout the RCP period in the pH group than in the alpha group. Furthermore, tissue oxygen saturation returned to its baseline level as soon as rewarming began in the pH group, whereas in the alpha group it did not return to baseline until 45 minutes after complete rewarming and normothermic CPB (Fig 3, C). There was no significant difference in brain oxygen extraction between the pH and alpha groups.

Brain tissue water content
There was no increase in tissue water content in either the alpha group (78.9% ± 0.3%) or the pH group (79.4% ± 0.2%) relative to control pigs (78.70% ± 0.15%) in normal control pigs [11]. There was no difference in tissue water content between the alpha and pH groups.

Histopathology
Neuronal injury was observed primarily in the cortical and striatum regions of the brain in both experimental groups. Total brain injury, evaluated as the sum of grades obtained from seven regions of the brain, appeared to be higher in the alpha group than in the pH group (11.1 versus 7.6). The difference did not reach statistical significance.


   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 References
 
Retrograde cerebral perfusion has been considered to provide metabolic substrates and oxygen to the brain during HCA. It is widely used as an adjunct to HCA in the repair of aortic dissection and aneurysmal disease requiring an open aortic arch. Although some clinical reports [15, 16] have suggested that RCP in combination with HCA decreases the rate of stroke and operative mortality associated with aortic arch operation, reports on the efficacy of RCP for brain protection are inconsistent. Experimental and clinical studies have demonstrated that RCP provides limited nutrient flow to support cerebral metabolism during HCA [6–8, 17]. Our recent study has demonstrated that increasing RCP pressures from 20 to 25 mm Hg to 35 to 40 mm Hg during RCP with an open IVC significantly increases brain tissue blood flow without causing brain edema in a pig model [11]. However, the increased brain tissue blood flow is still insufficient to meet metabolic requirement during deep HCA. Brain protection may further be improved by increasing cerebral perfusion during RCP.

Use of a pH-stat strategy during hypothermia has been reported to (1) decrease brain metabolism [18–20]; (2) increase CBF [21–23]; (3) increase the rate of brain cooling [24]; and (4) counteract the hypothermia-induced left shift of the oxyhemoglobin dissociation curve [25], which may enhance oxygen availability. Theoretically, these advantages should also occur during hypothermic RCP and enhance brain protection during HCA. However, the {alpha}-stat strategy has been almost exclusively used for blood pH management during RCP in both clinical and experimental settings. A few studies have reported that use of a pH-stat strategy during cooling increases the prearrest cortical oxygen saturation, which leads to an increase in cortical oxygen supply during HCA [24] and consequently improves postoperative neurologic outcome after HCA [24, 26, 27]. However, for unknown reasons, the pH-stat strategy has not been used during hypothermic RCP. In this study, we have used a combination of laser flowmetry and NIR spectroscopy to investigate the effect of pH-stat strategy on brain tissue perfusion and oxygenation during RCP. We have clearly demonstrated that pH-stat during hypothermic RCP significantly increases brain tissue perfusion and improves tissue oxygenation, as indicated by higher regional cerebral blood flow and oxyhemoglobin level relative to the use of an {alpha}-stat strategy. Brain tissue blood flow during RCP was 2.5 to 4.5 times higher in pigs managed by the pH-stat strategy than in those that were managed by the {alpha}-stat strategy. The higher oxyhemoglobin levels and lower deoxyhemogolobin levels observed throughout 120 minutes of RCP with the pH-stat strategy clearly resulted from improved brain tissue blood flow, but may also indicate increased oxygen storage (indicated by supernormal levels of tissue oxyhemoglobin and oxygen saturation) before initiating RCP and a decrease in brain oxygen metabolic rate during RCP.

With the use of pH-stat, hypercapnic dilation of arterioles and arteries would decrease the forward flow resistance during RCP. This may help retrograde blood flow through the brain tissue because the driving/perfusion pressure during RCP is very low. However, the exact mechanism by which a pH-stat strategy improves brain tissue perfusion during RCP is not known.

Relative to the {alpha}-stat strategy, use of the pH-stat strategy during cooling maintains significantly higher brain tissue flow, which may be greater than required for brain metabolic requirements. This is known as "luxury perfusion" [28, 29]. In this study, NIR spectroscopy showed that the levels of brain tissue oxyhemoglobin and tissue oxygen saturation during cooling were significantly higher than normal, indicating luxury oxygen supply. This may result in more oxygen storage in tissue before RCP and enhance oxygen availability, particularly during the initial period of RCP. A unique advantage of applying pH-stat during hypothermic CPB is that it improves oxygen availability by counteracting the leftward shift of oxyhemoglobin dissociation curve induced by hypothermia, which may play a key role in preventing tissue hypoxia during the early cooling phase when the brain is warm [30]. Initiation of the pH-stat strategy at the beginning of hypothermic CPB also improves global and regional cooling of the brain as a result of cerebral vasodilatation [31].

A further advantage of the pH-stat strategy is that it enhances the recovery of regional cerebral blood flow during rewarming. Hypoperfusion or hypoxia during rewarming is extremely detrimental to the brain, since oxygen is required to replenish the deficits accumulated during HCA and to repair tissues after HCA. In this study, brain tissue blood flow during rewarming was significantly higher and returned to baseline more quickly after initiating rewarming with the pH-stat strategy than with the {alpha}-stat strategy. Furthermore, tissue oxygen saturation remained below normal during rewarming and the initial period of normothermic CPB with the use of an {alpha}-stat strategy. Since brain tissue blood flow was similar between the two groups during normothermic CPB following rewarming, low tissue oxyhemoglobin and oxygen saturation in the alpha-stat group may indicate more oxygen consumption, probably due to oxygen starvation during the rewarming period. Histopathology has also shown that use of the pH-stat strategy reduces brain injury relative to the {alpha}-stat strategy.

The disadvantages of using a pH-stat strategy during hypothermic CPB include increased CBF that may increase brain emboli, and decreased pH that may suppress enzyme activity. However, RCP itself is able to flush out cerebral emboli, and suppression of enzyme activity may not be a concern because it is already very limited under deep hypothermia.

This study has some intrinsic limitations. As a result of anatomical differences between humans and animals, and the use of an acute porcine model, our data may not be completely translated into clinical situations. However, animal models provide controlled experimental conditions and allow measurements that often are not feasible in humans. The present study provides a detailed report on regional cerebral blood flow and brain tissue oxygenation during RCP with different methods of pH management. A chronic animal model would be ideal to evaluate delayed neurologic changes that cannot be measured in an acute study. A chronic animal model will be considered to allow assessment of neurologic functions.

In this study, the NIR probe was placed directly against the dura through a small window in the skull, and therefore no signals would be picked up from the skin and skull. The limitation of NIR spectroscopy is that it measures oxyhemoglobin or deoxyhemoglobin from all the vasculature, not just from capillaries. Therefore, it may not be sufficiently sensitive to detect small changes in either oxyhemoglobin or deoxyhemoglobin. However, NIR provides useful information on the general status of tissue oxygenation.

The aim of this study was to follow changes in regional brain tissue blood flow and oxygenation in real time to determine the effects on brain tissue perfusion and oxygenation of pH-stat and {alpha}-stat management during RCP. Therefore, we felt that it was not necessary to include two hypothermic circulatory arrest alone control groups. From previous studies, we know that 120 minutes of hypothermic circulatory arrest alone results in more severe brain damage than does 120 minutes of RCP.

In conclusion, in our pig model, the use of a pH-stat strategy during RCP significantly improves brain tissue perfusion and oxygenation, leading to less brain injury. Therefore, to improve the efficacy of brain protection during RCP, it may be preferable to use a pH-stat strategy, rather than an {alpha}-stat strategy. Further studies are necessary to determine the optimal conditions for RCP.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
References
 
This work was supported in part by the Canadian Institutes of Health Research (grant nos. 15352 and 42671 to Dr Ye) and the Manitoba Health Research Council through grants (to Dr Ye). We thank Jennifer Cherkas, Lori Gregorash, Amber Stoyko, Rachelle Mariash, and Shelley Germscheid for technical assistance. We also thank Dr Mike Sowa for his assistance in the analysis of NIR spectra.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

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