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© 1999 International Anesthesia Research Society
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Abstract |
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Cerebral air embolism can cause cerebral complications after open heart surgery. The duration of cerebral artery occlusion by air embolism is thought to vary depending on the conditions. However, no study has evaluated factors affecting the duration of occlusion. In this study, we examined the effects of blood pressure and hemodilution on the duration of retinal artery occlusion caused by air embolism in dogs. The duration of retinal artery occlusion caused by the injection of 0.6 mL of air into the common carotid artery was measured by fluorescein angiography and compared among the following three periods: a control period, during which the mean blood pressure (MBP) was maintained at 80 mm Hg; a hypotension period, during which MBP was decreased to 60 mm Hg by exsanguination; and a hypotension plus hemodilution period, during which an additional exchange of blood with hydroxyethyl starch solution was performed and MBP was maintained at 60 mm Hg. When MBP was lowered from 80 to 60 mm Hg, the duration of retinal artery occlusion was prolonged from 34 ± 39 to 166 ± 90 s (P < 0.01). In dogs with MBP of 60 mm Hg, hemodilution (12.0 ± 0.9 to 7.3 ± 0.5 g/dL hemoglobin concentration) shortened the duration from 166 ± 90 to 75 ± 50 s (P < 0.05). Our results demonstrate that hypotension prolongs and hemodilution shortens the duration of retinal artery occlusion caused by air embolism.
Implications: We evaluated the effects of blood pressure and hemodilution on the duration of retinal artery occlusion caused by air embolism by retinal fluorescein angiography. Hypotension prolonged and hemodilution shortened the duration of retinal artery occlusion caused by air embolism.
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Introduction |
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Cerebral dysfunction is one of the most serious sequelae of cardiac surgery using cardiopulmonary bypass (CPB) and has been studied extensively (1–4). Direct causes of cerebral dysfunction include hypoperfusion of the brain, hypoxemia, and cerebral embolism caused by air or thrombus, but the pathogenesis of this condition usually involves other factors, such as age, concurrent disease, and operative procedures. Although it is difficult to identify the exact cause in most cases, cerebral air embolism is one of the most probable causes of cerebral dysfunction. Although it is unclear whether microbubbles in the left heart contribute to cerebral dysfunction by formation of cerebral air embolism (5,6), a long period of cerebral artery occlusion due to air embolism could cause hypoxic damage of the brain.
The retinal artery lies peripheral to the ophthalmic artery, the first branch of the internal carotid artery after entering the cranium. Embryologically and anatomically, this artery resembles the cerebral arteries. Physiologically, the retinal artery resembles the cerebral arteries in many respects, such as the autoregulation of blood flow (7,8) and the effects of hemodilution (9–11), carbon dioxide (12), and oxygen (13) on blood flow. Halothane also increases retinal blood flow (14). In addition, the retinal artery can be readily observed from outside the body by using a fundus camera and can be used as an easily accessible surrogate model to study cerebral blood flow. More detailed information about the retinal artery can be obtained by using fluorescein angiography. Blouth et al. (15,16) used this technique to evaluate cerebrovascular circulation in patients undergoing cardiac surgery and reported that CPB was associated with a high rate of retinal artery microembolism. Besides microembolism, histological studies in the dog have documented the presence of intravascular platelet-fibrin microaggregates in the retinal artery after CPB (15).
Although the pathological characteristics and the diagnostic implications of histological disturbances of the brain and the retina caused by air embolism have been described previously (15–17), no study has reported conditions that influence incidence and duration of air embolism in the cerebral circulation. Hypotension and hemodilution often occur during open heart surgery, and these two conditions can influence the behavior of the air embolism through physical and physiological mechanisms (1,11). In this study using retinal fluorescein angiography (RFA), we examined the effects of hypotension and hemodilution on the duration of the retinal artery occlusion (RAOC) caused by air injection into the common carotid artery in dogs.
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Methods |
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All experimental protocols were approved by the animal study committee of Yokohama City University School of Medicine.
Thirty dogs were used in the experiment. Anesthesia was induced with an IM injection of 15 mg/kg ketamine hydrochloride, followed by an IV injection of 15 mg/kg pentobarbital sodium, and it was maintained by pentobarbital with or without halothane (in Experiment 1) or by halothane (in Experiments 2 and 3). Dogs were tracheally intubated, and their lungs were ventilated to maintain end-expiratory carbon dioxide partial pressure around 40 mm Hg. Pancuronium bromide 1 mg was given by bolus IV and 1 mg/h continuously thereafter to facilitate mechanical ventilation.
A catheter was inserted into the right femoral artery to measure arterial blood pressure and to obtain arterial blood samples. A catheter with a temperature probe sensor (Swan Ganz Catheter 93A-131-7F; Baxter Co., Ltd., Irvine, CA) was inserted into the right femoral vein for infusion and body temperature monitoring. Subsequently, 10 mg of heparin was given IV followed by a continuous infusion of 10 mg/h to prevent occlusion of the catheters. An electric heater was used to maintain body temperature at 37°C. Heart rate, direct blood pressure, arterial blood gas variables, and hemoglobin concentration were monitored during the experiment. End-expiratory carbon dioxide partial pressure and halothane concentration were also monitored with an anesthetic gas monitor (Capnomac Ultima; Datex Co., Ltd., Helsinki, Finland).
For the injection of fluorescein solution and air, a 20-gauge (0.53-mm inner diameter) urokinase-coated catheter (Argyle Medicut UK-II catheter; Japan Sherwood Co., Ltd., Tokyo, Japan) was inserted retrogradely into the right lingual artery until its tip was positioned approximately 5 mm proximal from the bifurcation in the common carotid artery. Air was injected through the catheter at a rate of 7.5 mL/min.
A 3% solution of fluorescein isothiocyanate dextran (FITC-dextran) was used as the contrast drug and given via the catheter in the right common carotid artery. RFAs were obtained with a fundus camera PRO 1; Kowa Co., Ltd., Tokyo, Japan). The films were developed, printed, and examined for the existence of RAOC by two observers.
Standard RFAs were taken immediately after the bolus injection of 1 mL of FITC-dextran solution. Successive RFAs were taken at appropriate intervals after bolus injection of 1 mL, followed by a continuous infusion of 60 mL/h, FITC-dextran solution until completion of the RFA. The RFA was also obtained before the injection of air into the common carotid artery as a control.
Experiment 1: The Incidence of RAOC
To determine the appropriate volume of air and blood pressure to detect RAOC, we preliminarily studied the effects of the volume of air and changes in blood pressure on the incidence of RAOC. The dogs were divided into two groups: a control group (n = 9, 8.3 ± 1.2 kg) in which anesthesia was maintained with continuous infusion of pentobarbital 10 mg · kg-1 · h-1 so that the mean blood pressure (MBP) remained 
90 mm Hg, and a hypotensive group (n = 9, 11.3 ± 2.2 kg) in which the MBP was lowered to approximately 50 mm Hg by removal of blood and by inhalation of 1.5% halothane in addition to a continuous infusion of pentobarbital.
A bolus injection of 0.2, 0.4, and 0.6 mL of air was administered into the common carotid artery. Standard RFAs were obtained immediately after and 1, 2, 3, 5, and 10 min after the air injection. These RFAs were taken until 10 min elapsed or all RAOCs were resolved, and the air injections were separated by an interval of 30 min.
Experiment 2: The Effects of Hypotension and Hemodilution on the Duration of RAOC
The results of the preliminary study revealed low detection rates of arterial occlusion due to air embolism when the injected volume of air was small and when the MBP was 90 mm Hg. Therefore, in this study, the injected volume of air was 0.6 mL, and the MBP in the control condition was maintained at approximately 80 mm Hg. The duration of RAOC was evaluated by successive RFAs.
Successive RFAs were obtained in six dogs (10.5 ± 2.0 kg) immediately after the injection of 0.6 mL of air under the following three conditions: 1) control period when MBP remained stable at approximately 80 mm Hg for at least 30 min under halothane inhalation; 2) hypotension period when MBP remained stable at approximately 60 mm Hg for at least 30 min after exsanguination of approximately 20 mL/kg blood; 3) hypotension plus hemodilution period, when MBP remained stable at approximately 60 mm Hg for at least 30 min after the IV infusion of 6% hydroxyethyl starch in a volume equivalent to the bleeding volume, followed by additional exsanguination of approximately 20 mL/kg blood. End-expiratory halothane concentrations were maintained at approximately 1% throughout the study. The duration of RAOC was defined as the time from the appearance to the resolution of all defects on the successive RFAs (Fig. 1).
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Experiment 3: The Effect of Repeated Air Injections
The effects of repeated air injections on the duration of RAOC were examined in separate experiments to rule out any influences from sequence- and time-dependent changes in the duration of RAOC during three successive periods. Successive RFAs were obtained in six dogs (12.4 ± 1.9 kg) immediately after the injection of 0.6 mL of air, and this procedure was repeated three times every 30 min while MBP was maintained at approximately 80 mm Hg under halothane anesthesia.
Statistical Analyses
All data are presented as means ± SD. Comparisons between incidences of RAOC were made by using the 
2 test with Yates' correction. Values among the three periods were compared by repeated-measures analysis of variance, and multiple comparisons were made by using Fisher's paired least significant difference test. P values <0.05 were considered to indicate statistical significance.
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Results |
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In Experiment 1, three experiments using 0.6 mL of air (two in control group and one in hypotensive group) were excluded from analysis because of technical failures producing unclear RFAs. In the control group, MBP was 115 ± 19 mm Hg. The incidences of RAOC caused by the injection of 0.2, 0.4, and 0.6 mL of air were 56%, 71%, and 71%, respectively (Table 1). There was a trend toward a low detection rate of RAOC immediately after the injection of a small volume (0.2 mL) of air. One minute after the air injection, RAOC had disappeared in all dogs.
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In the hypotensive group, RAOC was found in all dogs immediately after the injection of 0.2, 0.4, and 0.6 mL of air with MBP 50 ± 2 mm Hg (Table 1). Hypotension increased the incidences of RAOC significantly 1 min after the injections of 0.2, 0.4, and 0.6 mL of air compared with the control group. Despite a trend toward a positive correlation between the volume of air injected and the incidence of RAOC under hypotension, the only significant difference in incidence of RAOC was found between the injection volumes of 0.2 and 0.6 mL of air 3 min after the injection (Table 1).
These results indicate that MBP in the control group was too high to detect RAOCs constantly even if 0.6 mL of air was injected and that hypotension seemed to prolong the duration of RAOCs. Accordingly, we maintained MBP before interventions at approximately 80 mm Hg and used 0.6 mL of air for injection.
In Experiment 2, the duration of RAOC was evaluated by successive RFAs after the injection of 0.6 mL of air. RAOC was observed in all six dogs after all three repeated air injections, except for one dog during the control period and another during the hypotension plus hemodilution period. We assigned 0 s as the duration of RAOC in the absence of RAOC. As for the effect of hypotension induced by exsanguination of 20 mL/kg, MBP dropped significantly, from 78.3 ± 1.9 to 59.3 ± 2.3 mm Hg, but there was no change in the blood hemoglobin concentration (Table 2). This approximately 25% decrease in MBP was accompanied by a significant prolongation of the duration of RAOC, from 34 ± 39 to 166 ± 90 s (Table 2). Heart rate increased slightly but not significantly. There were no significant fluctuations in any other variable during hypotension period (Table 2).
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After hemodilution, the hemoglobin concentration decreased significantly from 12.0 ± 0.9 to 7.3 ± 0.5 g/dL, with no fluctuations in MBP (Table 2). This approximately 40% decrease in hemoglobin concentration was associated with significant shortening of the duration of RAOC caused by the injection of 0.6 mL of air (from 166 ± 90 to 75 ± 50 s) (Table 2). There were no significant fluctuations in any other variables during the hypotension plus hemodilution period (Table 2).
Three to five main branches of the retinal artery were identified in the field studied in these experiments. We counted the number of the branches blocked by air to estimate the amount of air emboli. Whereas 3.5 ± 1.9 branches were blocked in the control period, 4.2 ± 0.8 and 3.2 ± 1.7 branches were occluded in the hypotension and hypotension plus hemodilution periods. There was no statistically significant difference in these numbers among the three periods.
In Experiment 3, there were no significant fluctuations in hemodynamic variables, hemoglobin concentration, blood temperature, end-expiratory halothane concentration, or arterial blood gas variables during three repeated injections of 0.6 mL of air. RAOC was detected after all air injections. The duration of RAOC was unaffected by repeated injections of 0.6 mL of air (Table 3).
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Discussion |
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We used retinal air embolism as a model for cerebral air embolism and used fluorescein angiography to study the effects of hypotension and hemodilution on the duration of RAOC. The occlusion time was prolonged in the presence of decreased blood pressure, and this prolongation of occlusion time was partially restored by hemodilution in hypotensive dogs. Our results thus imply that hypotension may prolong and that hemodilution may shorten the duration of cerebral arterial occlusion due to air embolism, assuming that air emboli in retinal and cerebral circulation behave in a similar manner.
Because repeated air injections did not influence the duration of RAOC, changes in the duration of RAOC associated with hypotension and hemodilution were caused directly by these interventions, but not by repeated air injection. Besides blood pressure and hemodilution, retinal blood flow may be affected by other factors. For example, retinal blood flow increases in response to an increase in carbon dioxide partial pressure (12), decreases with an increase in oxygen partial pressure (13), and increases with halothane (14). However, as the partial pressures of carbon dioxide and oxygen in arterial blood and the end-expiratory halothane concentration were maintained at stable levels in Experiment 2, it is unlikely that these factors contributed to the changes in the duration of RAOC.
Because we injected air into the common carotid artery, a certain fraction of injected air entered the internal carotid artery. It is possible that the fraction of injected air entering the retinal circulation varies depending on blood pressure and the extent of hemodilution. Although evaluating the amount of air emboli is difficult, the finding that the numbers of the branches blocked by air were not significantly different among the three periods in Experiment 2 suggests that a similar volume of air entered the retinal artery. However, we cannot rule out the possibility that the amount and size of air emboli entering the retinal circulation varied among the three periods and that the differences in these factors contributed to the results.
Previous studies have shown that air embolism causes endothelial dysfunction, which disturbs blood flow even after the disappearance of air in cerebral and retinal circulation (17–19). In the present experiment, heparin was used to prevent blood clotting. Heparin might alter the duration of arterial occlusion by air by influencing the interaction of air with the vessels. Kochanek et al. (19) reported that platelet adhesion to endothelial cells after cerebral air embolism could not be prevented even with aggressive anti-platelet aggregation and anti-clotting treatment using prostacyclin, indomethacin, and heparin. In our study, RAOC was still observed even 10 min after the injection of 0.2 mL of air under hypotension, which suggests that endothelial cell dysfunction caused by air embolism may play a role. Heparin is also present during CPB, and most cerebral microemboli detected by transcranial Doppler ultrasound are observed during CPB in open heart surgery (20,21). Therefore, our study might mimic the clinical setting in this regard. However, larger doses of heparin given for CPB may exert different influences.
This model has several limitations in regard to applying the results obtained in this study to cerebral air embolism during CPB surgery. Several differences besides differences in the dose of heparin between this model and clinical conditions should be considered. The experiment was not performed during CPB, and the results were obtained in normothermic but not in hypothermic conditions. The size of air emboli in our model is probably larger than that in clinical settings. In addition, the retinal circulation, but not cerebral circulation, was studied, and neither neurological nor histopathological findings were investigated in the experiment.
Nonpulsatile flow during CPB should profoundly affect the behavior of air emboli in both cerebral and retinal circulation. However, it has been reported that most cerebral microembolic signals in the middle cerebral artery were detected when the heart regained effective ejection during CPB in valve replacement (20,21). This finding suggests that microemboli detected by transcranial Doppler ultrasound are likely to be of gaseous form, originating from cardiac chambers in this type of surgery, and that embolic events predominantly occur in the period of mixture of nonpulsatile and pulsatile circulation. Therefore, although the hemodynamics during this period may be different from those in our study, pulsatile circulation is partially restored during the period in which cerebral air embolism most frequently occurs.
Body temperature may also affect the duration of arterial occlusion caused by air. However, when air goes into cerebral circulation, patients are often rewarmed close to the normal body temperature, considering the reports mentioned above (20,21). It is also possible that a small difference in body temperature can change the fate of air emboli.
In Experiment 2, the volume of air injected was 0.6 mL, and relatively large retinal arterioles measuring approximately 0.1–0.2 mm in diameter were used for observation. Although it is not clear what volume of air and what size of bubbles go into the common carotid artery during open heart surgery, the microbubbles frequently observed in the left heart on echocardiography are considered to be the putative source of cerebral emboli during open heart surgery (5,6). They may occlude smaller arteries, and the influences of the blood pressure or hemodilution may differ from those in our study.
Although retinal circulation is similar in many aspects to cerebral circulation, the extrapolation of the findings of this study to cerebral air embolism should be verified by the further studies. Moreover, investigations of neuropsychological outcome and histopathological findings will be required to prove adverse effects of hypotension and beneficial effects of hemodilution on cerebral air embolism.
A decrease in MBP from 80 to 60 mm Hg may not appreciably affect blood flow because of the autoregulation capacity of the retinal artery (7,8). Although halothane anesthesia may affect autoregulation mechanisms (22) and cause a blood pressure-dependent decrease in blood flow, this change might be small. However, an approximately 25% decrease in blood pressure prolonged the duration of RAOC due to air embolism by approximately fivefold. Therefore, the disappearance of air embolism might be affected by the perfusion pressure of this level, as well as by blood flow in the retinal artery. Gold et al. (1) reported that the postoperative neurological outcome was better when perfusion pressure during CPB was maintained at a high level of 80–100 mm Hg, rather than at the conventional level of 50–60 mm Hg, although the difference did not reach statistical significance. They claimed that the blood pressure range within which autoregulation of blood flow occurs was narrower than generally accepted values, and that a higher perfusion pressure effectively promoted autoregulation, resulting in stable blood flow. In addition, promotion of resolution of air embolism by high perfusion pressure itself may also play a part in this phenomenon.
Similar to cerebral blood flow, retinal blood flow is also increased by hemodilution with hydroxyethyl starch (9–11). Although the mechanism responsible for the increased blood flow is unknown, simple hydrostatic changes due to decreased blood viscosity and compensatory vasodilation in response to reduced oxygen content are apparently involved (23). Hemodilution most likely promoted resolution of air embolism primarily by increasing blood flow in the present experiment, although inhibition of platelet aggregation may also have been a factor.
In conclusion, the results of this study show that hypotension prolongs and hemodilution shortens the duration of RAOC caused by air embolism. It remains to be determined whether blood pressure and hemodilution exert the same effects on cerebral air embolism during the CPB surgery.
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Acknowledgments |
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This study was supported in part by the Ministry of Education, Science and Culture Grant B-04454392.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Gold JP, Charlson ME, Williams-Russo P, et al. Improvement of outcomes after coronary artery bypass. J Thorac Cardiovasc Surg 1995;110:1302–14.
[Abstract/Free Full Text] - Kuroda Y, Uchimoto R, Kaieda R, et al. Central nervous system complications after cardiac surgery : a comparison between coronary artery bypass grafting and valve surgery. Anesth Analg 1993;76:222–7.[Web of Science][Medline]
-
Johnston WE, Stump DA, DeWitt DS, et al. Significance of gaseous microemboli in the cerebral circulation during cardiopulmonary bypass in dogs. Circulation 1993;88:319–29.
[Free Full Text] - Moody DM, Bell MA, Challa VR, et al. Brain microemboli during cardiac surgery or aortography. Ann Neurol 1990;28:477–86.[Web of Science][Medline]
- Rodigas PC, Meyer FJ, Haasler GB, et al. Intraoperative 2-dimensional echocardiography : ejection of microbubbles from the left ventricle after cardiac surgery. Cardiol 1982;50:1130–2.
- Oka Y, Inoue T, Hong Y, et al. Retained intracardiac air : transesophageal echocardiography for definition of incidence and monitoring removal by improved techniques. J Thorac Cardiovasc Surg 1986;91:329–38.[Abstract]
-
Tachibana H, Gotoh F, Ishikawa Y. Retinal vascular autoregulation in normal subjects. Stroke 1982;13:149–55.
[Abstract/Free Full Text] - Riva CE, Grunwald JE, Petrig BL. Autoregulation of human retinal blood flow : an investigation with laser Doppler velocimetry. Sci 1986;27:1706–12.
-
Perez-Trepichio AD, Furlan AJ, Little JR, Jones SC. Hydroxyethyl starch 200/0.5 reduces infarct volume after embolic stroke in rats. Stroke 1992;23:1782–91.
[Abstract/Free Full Text] -
Yamauchi H, Fukuyama H, Ogawa M, et al. Hemodilution improves cerebral hemodynamics in internal carotid artery occlusion. Stroke 1993;24:1885–90.
[Abstract/Free Full Text] - Roth S. The effects of isovolumic hemodilution on ocular blood flow. Exp Eye Res 1992;55:59–63.[Web of Science][Medline]
-
Tsacopoulos M, David NJ. The effect of arterial PCO2 on relative retinal blood flow in monkeys. Invest Ophthalmol 1973;12:335–47.
[Abstract/Free Full Text] -
Pakola SJ, Grunwald JE. Effects of oxygen and carbon dioxide on human retinal circulation. Invest Ophthalmol Vis Sci 1993;34:2866–70.
[Abstract/Free Full Text] - Roth S. The effects of halothane on retinal and choroidal blood flow in cats. Anesthesiology 1992;76:455–60.[Web of Science][Medline]
- Blauth CI, Arnold JV, Schulenberg WE, et al. Cerebral microembolism during cardiopulmonary bypass : retinal microvascular studies in vivo with fluorescein angiography. J Thorac Cardiovasc Surg 1988;95:668–76.[Abstract]
- Blauth CI, Smith PL, Arnold JV, et al. Influence of oxygenator type on the prevalence and extent of microembolic retinal ischemia during cardiopulmonary bypass : assessment by digital image analysis. J Thorac Cardiovasc Surg 1990;99:61–9.[Abstract]
-
Ring HG, David NJ. Experimental air embolism : studies with fluorescein cinematography. Arch Ophthalmol 1969;81:830–6.
[Abstract/Free Full Text] -
Helps SC, Parsons DW, Reilly PL, Gorman DF. The effect of gas emboli on rabbit cerebral blood flow. Stroke 1990;21:94–9.
[Abstract/Free Full Text] -
Kochanek PM, Dutka AJ, Kumaroo KK, Hallenbeck JM. Effects of prostacyclin, indomethacin, and heparin on cerebral blood flow and platelet adhesion after multifocal ischemia of canine brain. Stroke 1988;19:693–9.
[Abstract/Free Full Text] - van der Linden J, Casimir-Ahn H. When do cerebral emboli appear during open heart operations? A transcranial Doppler study. Ann Thorac Surg 1991;51:237–41.[Abstract]
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Brekken SK, Russel D, Brucher R, et al. Cerebral microembolic signals during cardiopulmonary bypass surgery : frequency, time of occurrence, and associations with patient and surgical characteristics. Stroke 1997;28:1988–92.
[Abstract/Free Full Text] - Morita H, Nemoto EM, Bleyaert AL, Stezoski SW. Brain blood flow autoregulation and metabolism during halothane anesthesia in monkeys. Am J Physiol 1977;233:H670–6.
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Korosue K, Heros RC. Mechanism of cerebral blood flow augmentation by hemodilution in rabbits. Stroke 1992;23:1487–93.
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