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Retrograde cerebral perfusion: Is the brain really being perfused?
Journal of
Cardiothoracic and Vascular Anesthesia VOL 12, NO 3
JUNE 1998
EDITORIAL Retrograde Cerebral Perfusion: Is the Brain Really Being Perfused?
p
ROTECTION OF THE BRAIN during procedures in which its arterial supply is interrupted has been an ongoing dilemma since the earliest clinical report by DeBakey et al, 1 in 1957, of successful aortic arch replacement using selective cerebral perfusion. Subsequently, the initial enthusiasm for selective cerebral perfusion through the brachiocephalic vessels gave way to increasing concerns about the excessively high risk for stroke and mortality associated with such procedures, related to the extensive dissection and mobilization of extracranial vessels required and the attendant risks of cerebral air embolism.2 For the record, however, two recent clinical series showed the ongoing interest in selective cerebral perfusion, reporting good outcomes with this approach during circulatory arrest. 3,4 A clinical counterpoint to such relatively complicated techniques was first reported by Borst et al5 and outlined the successful sole use of deep hypothermic circulatory arrest (DHCA) for aortic arch surgery. Coupled with the subsequent report by Griepp et al6 describing the benefit of topical cooling of the head in conjunction with systemic hypothermia before DHCA, this approach became the standard of care for many North American cardiovascular centers. In 1990, however, Ueda et al7 described the use of retrograde cerebral perfusion (RCP) through a superior vena cava (SVC) cannula as a relatively simple adjunct to DHCA for aortic arch surgery. Two articles in this issue of the Journal of Cardiothoracic and Vascular Anesthesia highlight the differing strategies currently used to deal with the problem of brain protection in situations in which circulatory arrest is required. In a retrospective review, Appoo et al8 documented their experience with 50 adult patients who underwent DHCA, primarily for repair of aortic disease. Using techniques essentially unchanged from those initially reported by Griepp et al6 more than 2 decades ago, this group used systemic hypothermia in conjunction with ice packing of the head and thiopental administration for periods of DHCA averaging 18 minutes and ranging up to 42 minutes in duration. They reported an overall perioperative mortality rate of 8% and an incidence of neurologic morbidity of 6%, A different approach to this problem is reported by Cheung et al.9 They used RCP by selective cannulation of the SVC in 15 patients who underwent periods of DHCA averaging 36 minutes in duration, with RCP used for an average of 27 minutes, and compared this with their experience with three more patients in whom DHCA without RCP was used. One of 15 patients (6%) who underwent RCP had
new-onset hemiparesis, and two other patients showed transient postoperative confusion. Using analysis of somatosensory evoked potentials (SSEPs), they reported that RCP attenuated the rate of decay of SSEP amplitudes during DHCA, implying a beneficial effect of RCP on the central nervous system. With the exception of trickle flow under certain conditions in specific experimental models, it is generally true that some perfusion to the brain is better than none. The repeated clinical evidence of the feasibility of retrograde perfusion during DHCA would therefore appear to close the issue, but for some lingering reservations. Because of significant species differences in the venoarterial architecture of the brain, which include the presence of venous valves and less numerous and less extensive venovenous anastomoses in the head and neck of the dog, the most common species for studies of RCP and a cerebral arterial supply with much greater variability in collateral perfusion than that found in the human brain, many of the studies of RCP in animals have resorted to various strategies to overcome these species differences that potentially limit the clinical interpretability of their results. Maxillary vein cannulation,~° direct sagittal vein cannulation,1~ and specific destruction of jugular venous valves ~2 have all been used to overcome some of these difficulties. These approaches have limited clinical application, however. Studies of RCP in nonhuman primates can most closely approximate conditions in the human brain because of the anatomic similarity of the venous system in all primates. In a study of RCR Boeckxstaens and Flameng13 cooled 19 baboons to 18°C, measured brain biochemical markers, and used colored microspheres to assess cerebral blood flow (CBF). Six animals were treated soley with DHCA for 60 minutes, whereas 13 others underwent DHCA with RCP through bilateral internal jugular vein (IJV) cannulae at venous pressures of 20 mmHg. Release of brain-specific isoenzyme creatine kinase-BB was similar in both groups, as were arteriovenous differences in glucose uptake and lactate production. Histologic signs of neuronal damage were also similar in both groups, although slightly more glial edema was found in RCP-treated animals. During RCR less than 1% of the blood perfused through the RCP cannulae returned by the aortic arch. At the end of 60 minutes of RCR this value had decreased to less than 0.1% of total perfusate. Measurement of CBF during RCP indicated that blood flow was at the extreme lower limit of detection: global CBF was 0.5 mL/min/100 g, less than 2% of the value measured during antegrade perfusion at the same temperature. These
Journal o f Cardiothoracic and VascularAnasthesia, Vol 12, No 3 (June), 1998: pp 249-251
249
250
JOHN M. MURKIN
investigators concluded that during RCP in primates, even with cannulation beyond the venous valves, massive shunting of blood occurs at the level of multiple venovenous anastomoses between deep and superficial venous drainage systems of the head. These include large connections between the internal and external jugular veins, and between those veins and the venous system of the spinal cord. 13 Similar venovenous anastomoses exist in the human brain. 14 The presence of intact valves bilaterally within the IJV has also been identified in 84% to 100% of subjects in various autopsy series. 14,15In vitro, valves within the IJV, generally located 2 cm to 3 cm superior to the junction point with the subclavian vein, have been shown to be competent up to static pressures of 100 mmHg. 16 Therefore, unless these are rendered incompetent by disease or selective IJV cannulation, retroperfusion via the SVC alone is unlikely to reach the brain. In studies in humans the critical role of the azygos vein, rather than the IJV, during retroperfusion has been shown in an anatomic study in cadavers. ~5The azygos vein was found to act as a conduit to the cerebral circulation by its connections to the vertebral venous system and the venous plexus of the foramen magnum and intracranial sinuses. Using latex injection through a catheter in the SVC, in cadavers in which the IJV valves were competent and the azygos had been ligated, no injectate was found in the cerebral venous system versus significant cerebral vascular filling if the azygos was patent. 15 In vivo, clinical evidence for cerebral perfusion occurring during RCP was provided by Pagano et al. t7 These investigators used radioisotopic technetium-labeling in three patients who underwent RCR and they were able to show progressive accumulation of the tracer in brain substance over time. Crucially, whereas these studies do show evidence of some cerebral perfusion during RCR whether it is sufficient for the metabolic demands of the brain remains in doubt. As cogently discussed by Griepp et al,t8 the use of various process variables as endpoints in laboratory studies of RCR such as metabolic parameters, cerebral oxygen content, and degree of cerebral edema, bears an uncertain relationship to neuronal integrity and ultimate functional outcome. Using a pig model of DHCA at 20°C, histologic examination revealed superiority of RCP over DHCA even with ice packing of the head, although functional outcome was equally good with either technique. 19 In assessing the utility of RCP in the presence of cerebral emboli, however, this group identified that under some circumstances, RCP might actually aggravate cerebral injury. 2° Use of high SVC pressures or occlusion of the inferior vena cava during RCP was associated with evidence of injury that occurred in the postoperative rather than the intraoperative period, leading to speculation that the late development of cerebral edema was a consequence of RCP-related injury. ~8
Others have made similar observations. In a study of RCP in dogs at 20°C, 120 minutes of RCP through the internal maxillary veins was associated with increased intracranial pressure, cerebral edema, and increased cerebrovascular resistance in control animals during antegrade reperfusion compared with those animals receiving mannitol or an antivasospastic agent. 2t Whether such adjunctive therapy should be considered during RCP is currently unclear. In the clinical setting, retropeffusion through an SVC cannula has become an established technique in many centers. In a recent retrospective review of 228 patients who underwent RCP at 49 institutions in Japan, the investigators identified RCP that exceeded 60 minutes as second only to preoperative cardiac arrest as the most significant predictor of permanent neurologic dysfunction. 22 Consistent with this, many investigators now consider that cerebral perfusion by RCP and the supply of oxygen and glucose substrate to the brain are not sufficient to maintain cerebral metabolism at optimal levels during circulatory arrest, even in the presence of moderate hypothermia. 18,2°,2l Much of the apparent benefit of RCP that has been reported in clinical series and laboratory studies likely reflects the persistence of brain cooling and the prevention of slow brain rewarming that generally accompanies prolonged DHCA, rather than adequacy of blood flow to the brain.18 This is not to say that the technique of RCP does not work or that it should not be used. In fact, clinical experience and experimental studies have shown that, within limits, RCP does have a role during circulatory arrest, if such technical issues as valvulation of the IJV, the potential for hydrostatic pressure injury to the brain, and the relatively low level of substrate supply actually provided by RCP are borne clearly in mind. Some investigators consider the ultimate benefit of RCP to be its use to ameliorate neurologic injury in the presence of particulate cerebral embolization. 18 For others, the inherent attraction of RCP as a potential alternate means of brain perfnsion has given rise to separate applications. A recent nonrandomized clinical report that outlined the preliminary results of RCP by selective transverse sinus cannulation in eight patients who presented with signs and symptoms of acute ischemic stroke showed some significant improvement in symptomatology in some of the patients so treated. 23 In all these various settings, it has been clearly established that RCP can be performed. The critical issue now is whether it should be performed. A randomized clinical trial is the only appropriate means to address this issue. John 34. Murkin, MD, FRCPC Professor of Anaesthesia University of Western Ontario London, Ontario, Canada
REFERENCES
1. DeBakey ME, Crawford CS, Cooley DA, Morris GC: Successful resection of fusiform aneurysm of aortic arch with replacement by homograft. Surg Gynecol Obstet 105:657-64, 1957 2. De Bakey ME: The development of vascular surgery. Am J Surg 173:697-738, 1979 3. Alamanni F, Agrifoglio M, Pompilio G, et al: Aortic arch
surgery: Pros and cons of selective cerebral perfusion. A multivariable analysis for cerebral injury during hypothermic circulatory arrest. J Cardiovasc Surg (Torino) 36:31-37, 1995 4. Tabayashi K, Ohmi M, Togo T, et al: Aortic arch aneursym repair using selective cerebral perfusion. Ann Thorac Surg 57:1305-1310, 1994
EDITORIAL
5. Borst HG, Shaudig A, RandoIph W: Arteriovenous fistula of the aortic arch: Repair during deep hypothermia and circulatory arrest. J Thorac Cardiovasc Surg 48:443-447, 1964 6. Greipp RB, Stinson EB, Hollingsworth JF, Buehler D: Prosthetic replacement of the aortic arch. J Thorac Cardiovasc Surg 70:1051 - 1063, 1975 7. Ueda Y, Miki S, Kusuhara K, et al: Surgical treatment of aneurysm or dissection involving the ascending aorta and aortic arch, utilizing circulatory arrest and retrograde cerebral perfusion. J Cardiovasc Surg 31:553-558, 1990 8. Appoo JJ, Ralley F, Baslaim G, DeVarennes B: Anesthesia for deep hypothermic circulatory arrest in adults. A simple technique for short procedures: Experience with first 50 patients. J Cardiothorac Vasc Anesth 12:260-265, 1998 9. Cheung AT, Bavaria JE, Weiss SJ, et al: Neurophysiologic effects of retrograde cerebral perfusion employed for aortic reconstruction. J Cardiothorac ~asc Anesth 12:252-259, 1998 10. Oohara K, Usui A, Murase M, et al: Regional cerebral tissue blood flow measured by the colored microsphere method during retrograde cerebral perfusion. J Thorac Cardiovasc Surg 109:772-779, 1995 11. Watanabe T, Iijima Y, Abe K, et al: Retrograde brain perfusion beyond the venous valves: Hemodynamic and intracellular pH mapping. J Thorac Cardiovasc Surg 111:36-44, 1996 12. Usui A, Hotta T, Hiroura M, et al: Retrograde cerebral perfusion through a superior vena caval cannula protects the brain. Ann Thorac Surg 53:47-53, 1992 13. Boeckxstaens CJ, Flameng WJ: Retrograde cerebral perfusion does not perfuse the brain in nonhuman primates. Ann Thorac Surg 60:319-328, 1995
251
14. Ogata J, Feigin I: Arteriovenous communications in the human brain. J Neuropathol Exp Neurol 31:519-525, 1972 15. de Brux J-L, Subayi J-B, Pegis J-D, Pillet J: Retrograde cerebral perfusion: Anatomic study of the distribution of blood to the brain. Ann Thorac Surg 60:1294-1298, 1995 16. Dressler LR McKinney WM: Anatomic and pathophysiologic studies of the human internal jugular valve. Am J Surg 154:220-224, 1987 17. Pagano D, Boivin CM, Faroqui MH, Bonser RS: Retrograde perfusion through the superior vena cava perfuses the brain in human beings. J Thorac Cardiovasc Surg 111:270-272, 1996 18. Griepp RB, Juvonen T, Griepp EB, et al: Is retrograde cerebral perfusion an effective means of neural support during deep hypothermic circulatory arrest? Ann Thorac Surg 64:913-916, 1997 19. Midulla PS, Gandsas A, Sadeghi A, et al: Comparison of retrograde cerebral perfusion to antegrade cerebral perfusion and hypothermic circulatory arrest in a chronic porcine model. J Card Surg 9:560-575, 1994 20. Juvonen T, Weisz DJ, Wolfe D, et al: Can retrograde perfusion mitigate cerebral injury following particulate embolization? A study in a chronic porcine model. J Thorac Cardiovasc Surg (in press) 21. Yoshimnra N, Okada M, Ota T, Nohara H: Pharmacologic intervention for ischemic brain edema after retrograde cerebral perfusion. J Thorac Cardiovasc Surg 109:1173-1181, 1995 22. Usui A, Abe T, Murase M: Early clinical results of retrograde cerebral perfusion for aortic arch operations in Japan. Ann Thorac Surg 62:94-103, i996 23. Frazee J, Shiroishi M, Luo X, et al: A novel backdoor stroke therapy--Neuroperfusion. 22nd International Joint Conference on Stroke and Cerebral Circulation, February 8th, Anaheim, CA, 1997
Cardiothoracic and Vascular Anesthesia VOL 12, NO 3
JUNE 1998
EDITORIAL Retrograde Cerebral Perfusion: Is the Brain Really Being Perfused?
p
ROTECTION OF THE BRAIN during procedures in which its arterial supply is interrupted has been an ongoing dilemma since the earliest clinical report by DeBakey et al, 1 in 1957, of successful aortic arch replacement using selective cerebral perfusion. Subsequently, the initial enthusiasm for selective cerebral perfusion through the brachiocephalic vessels gave way to increasing concerns about the excessively high risk for stroke and mortality associated with such procedures, related to the extensive dissection and mobilization of extracranial vessels required and the attendant risks of cerebral air embolism.2 For the record, however, two recent clinical series showed the ongoing interest in selective cerebral perfusion, reporting good outcomes with this approach during circulatory arrest. 3,4 A clinical counterpoint to such relatively complicated techniques was first reported by Borst et al5 and outlined the successful sole use of deep hypothermic circulatory arrest (DHCA) for aortic arch surgery. Coupled with the subsequent report by Griepp et al6 describing the benefit of topical cooling of the head in conjunction with systemic hypothermia before DHCA, this approach became the standard of care for many North American cardiovascular centers. In 1990, however, Ueda et al7 described the use of retrograde cerebral perfusion (RCP) through a superior vena cava (SVC) cannula as a relatively simple adjunct to DHCA for aortic arch surgery. Two articles in this issue of the Journal of Cardiothoracic and Vascular Anesthesia highlight the differing strategies currently used to deal with the problem of brain protection in situations in which circulatory arrest is required. In a retrospective review, Appoo et al8 documented their experience with 50 adult patients who underwent DHCA, primarily for repair of aortic disease. Using techniques essentially unchanged from those initially reported by Griepp et al6 more than 2 decades ago, this group used systemic hypothermia in conjunction with ice packing of the head and thiopental administration for periods of DHCA averaging 18 minutes and ranging up to 42 minutes in duration. They reported an overall perioperative mortality rate of 8% and an incidence of neurologic morbidity of 6%, A different approach to this problem is reported by Cheung et al.9 They used RCP by selective cannulation of the SVC in 15 patients who underwent periods of DHCA averaging 36 minutes in duration, with RCP used for an average of 27 minutes, and compared this with their experience with three more patients in whom DHCA without RCP was used. One of 15 patients (6%) who underwent RCP had
new-onset hemiparesis, and two other patients showed transient postoperative confusion. Using analysis of somatosensory evoked potentials (SSEPs), they reported that RCP attenuated the rate of decay of SSEP amplitudes during DHCA, implying a beneficial effect of RCP on the central nervous system. With the exception of trickle flow under certain conditions in specific experimental models, it is generally true that some perfusion to the brain is better than none. The repeated clinical evidence of the feasibility of retrograde perfusion during DHCA would therefore appear to close the issue, but for some lingering reservations. Because of significant species differences in the venoarterial architecture of the brain, which include the presence of venous valves and less numerous and less extensive venovenous anastomoses in the head and neck of the dog, the most common species for studies of RCP and a cerebral arterial supply with much greater variability in collateral perfusion than that found in the human brain, many of the studies of RCP in animals have resorted to various strategies to overcome these species differences that potentially limit the clinical interpretability of their results. Maxillary vein cannulation,~° direct sagittal vein cannulation,1~ and specific destruction of jugular venous valves ~2 have all been used to overcome some of these difficulties. These approaches have limited clinical application, however. Studies of RCP in nonhuman primates can most closely approximate conditions in the human brain because of the anatomic similarity of the venous system in all primates. In a study of RCR Boeckxstaens and Flameng13 cooled 19 baboons to 18°C, measured brain biochemical markers, and used colored microspheres to assess cerebral blood flow (CBF). Six animals were treated soley with DHCA for 60 minutes, whereas 13 others underwent DHCA with RCP through bilateral internal jugular vein (IJV) cannulae at venous pressures of 20 mmHg. Release of brain-specific isoenzyme creatine kinase-BB was similar in both groups, as were arteriovenous differences in glucose uptake and lactate production. Histologic signs of neuronal damage were also similar in both groups, although slightly more glial edema was found in RCP-treated animals. During RCR less than 1% of the blood perfused through the RCP cannulae returned by the aortic arch. At the end of 60 minutes of RCR this value had decreased to less than 0.1% of total perfusate. Measurement of CBF during RCP indicated that blood flow was at the extreme lower limit of detection: global CBF was 0.5 mL/min/100 g, less than 2% of the value measured during antegrade perfusion at the same temperature. These
Journal o f Cardiothoracic and VascularAnasthesia, Vol 12, No 3 (June), 1998: pp 249-251
249
250
JOHN M. MURKIN
investigators concluded that during RCP in primates, even with cannulation beyond the venous valves, massive shunting of blood occurs at the level of multiple venovenous anastomoses between deep and superficial venous drainage systems of the head. These include large connections between the internal and external jugular veins, and between those veins and the venous system of the spinal cord. 13 Similar venovenous anastomoses exist in the human brain. 14 The presence of intact valves bilaterally within the IJV has also been identified in 84% to 100% of subjects in various autopsy series. 14,15In vitro, valves within the IJV, generally located 2 cm to 3 cm superior to the junction point with the subclavian vein, have been shown to be competent up to static pressures of 100 mmHg. 16 Therefore, unless these are rendered incompetent by disease or selective IJV cannulation, retroperfusion via the SVC alone is unlikely to reach the brain. In studies in humans the critical role of the azygos vein, rather than the IJV, during retroperfusion has been shown in an anatomic study in cadavers. ~5The azygos vein was found to act as a conduit to the cerebral circulation by its connections to the vertebral venous system and the venous plexus of the foramen magnum and intracranial sinuses. Using latex injection through a catheter in the SVC, in cadavers in which the IJV valves were competent and the azygos had been ligated, no injectate was found in the cerebral venous system versus significant cerebral vascular filling if the azygos was patent. 15 In vivo, clinical evidence for cerebral perfusion occurring during RCP was provided by Pagano et al. t7 These investigators used radioisotopic technetium-labeling in three patients who underwent RCR and they were able to show progressive accumulation of the tracer in brain substance over time. Crucially, whereas these studies do show evidence of some cerebral perfusion during RCR whether it is sufficient for the metabolic demands of the brain remains in doubt. As cogently discussed by Griepp et al,t8 the use of various process variables as endpoints in laboratory studies of RCR such as metabolic parameters, cerebral oxygen content, and degree of cerebral edema, bears an uncertain relationship to neuronal integrity and ultimate functional outcome. Using a pig model of DHCA at 20°C, histologic examination revealed superiority of RCP over DHCA even with ice packing of the head, although functional outcome was equally good with either technique. 19 In assessing the utility of RCP in the presence of cerebral emboli, however, this group identified that under some circumstances, RCP might actually aggravate cerebral injury. 2° Use of high SVC pressures or occlusion of the inferior vena cava during RCP was associated with evidence of injury that occurred in the postoperative rather than the intraoperative period, leading to speculation that the late development of cerebral edema was a consequence of RCP-related injury. ~8
Others have made similar observations. In a study of RCP in dogs at 20°C, 120 minutes of RCP through the internal maxillary veins was associated with increased intracranial pressure, cerebral edema, and increased cerebrovascular resistance in control animals during antegrade reperfusion compared with those animals receiving mannitol or an antivasospastic agent. 2t Whether such adjunctive therapy should be considered during RCP is currently unclear. In the clinical setting, retropeffusion through an SVC cannula has become an established technique in many centers. In a recent retrospective review of 228 patients who underwent RCP at 49 institutions in Japan, the investigators identified RCP that exceeded 60 minutes as second only to preoperative cardiac arrest as the most significant predictor of permanent neurologic dysfunction. 22 Consistent with this, many investigators now consider that cerebral perfusion by RCP and the supply of oxygen and glucose substrate to the brain are not sufficient to maintain cerebral metabolism at optimal levels during circulatory arrest, even in the presence of moderate hypothermia. 18,2°,2l Much of the apparent benefit of RCP that has been reported in clinical series and laboratory studies likely reflects the persistence of brain cooling and the prevention of slow brain rewarming that generally accompanies prolonged DHCA, rather than adequacy of blood flow to the brain.18 This is not to say that the technique of RCP does not work or that it should not be used. In fact, clinical experience and experimental studies have shown that, within limits, RCP does have a role during circulatory arrest, if such technical issues as valvulation of the IJV, the potential for hydrostatic pressure injury to the brain, and the relatively low level of substrate supply actually provided by RCP are borne clearly in mind. Some investigators consider the ultimate benefit of RCP to be its use to ameliorate neurologic injury in the presence of particulate cerebral embolization. 18 For others, the inherent attraction of RCP as a potential alternate means of brain perfnsion has given rise to separate applications. A recent nonrandomized clinical report that outlined the preliminary results of RCP by selective transverse sinus cannulation in eight patients who presented with signs and symptoms of acute ischemic stroke showed some significant improvement in symptomatology in some of the patients so treated. 23 In all these various settings, it has been clearly established that RCP can be performed. The critical issue now is whether it should be performed. A randomized clinical trial is the only appropriate means to address this issue. John 34. Murkin, MD, FRCPC Professor of Anaesthesia University of Western Ontario London, Ontario, Canada
REFERENCES
1. DeBakey ME, Crawford CS, Cooley DA, Morris GC: Successful resection of fusiform aneurysm of aortic arch with replacement by homograft. Surg Gynecol Obstet 105:657-64, 1957 2. De Bakey ME: The development of vascular surgery. Am J Surg 173:697-738, 1979 3. Alamanni F, Agrifoglio M, Pompilio G, et al: Aortic arch
surgery: Pros and cons of selective cerebral perfusion. A multivariable analysis for cerebral injury during hypothermic circulatory arrest. J Cardiovasc Surg (Torino) 36:31-37, 1995 4. Tabayashi K, Ohmi M, Togo T, et al: Aortic arch aneursym repair using selective cerebral perfusion. Ann Thorac Surg 57:1305-1310, 1994
EDITORIAL
5. Borst HG, Shaudig A, RandoIph W: Arteriovenous fistula of the aortic arch: Repair during deep hypothermia and circulatory arrest. J Thorac Cardiovasc Surg 48:443-447, 1964 6. Greipp RB, Stinson EB, Hollingsworth JF, Buehler D: Prosthetic replacement of the aortic arch. J Thorac Cardiovasc Surg 70:1051 - 1063, 1975 7. Ueda Y, Miki S, Kusuhara K, et al: Surgical treatment of aneurysm or dissection involving the ascending aorta and aortic arch, utilizing circulatory arrest and retrograde cerebral perfusion. J Cardiovasc Surg 31:553-558, 1990 8. Appoo JJ, Ralley F, Baslaim G, DeVarennes B: Anesthesia for deep hypothermic circulatory arrest in adults. A simple technique for short procedures: Experience with first 50 patients. J Cardiothorac Vasc Anesth 12:260-265, 1998 9. Cheung AT, Bavaria JE, Weiss SJ, et al: Neurophysiologic effects of retrograde cerebral perfusion employed for aortic reconstruction. J Cardiothorac ~asc Anesth 12:252-259, 1998 10. Oohara K, Usui A, Murase M, et al: Regional cerebral tissue blood flow measured by the colored microsphere method during retrograde cerebral perfusion. J Thorac Cardiovasc Surg 109:772-779, 1995 11. Watanabe T, Iijima Y, Abe K, et al: Retrograde brain perfusion beyond the venous valves: Hemodynamic and intracellular pH mapping. J Thorac Cardiovasc Surg 111:36-44, 1996 12. Usui A, Hotta T, Hiroura M, et al: Retrograde cerebral perfusion through a superior vena caval cannula protects the brain. Ann Thorac Surg 53:47-53, 1992 13. Boeckxstaens CJ, Flameng WJ: Retrograde cerebral perfusion does not perfuse the brain in nonhuman primates. Ann Thorac Surg 60:319-328, 1995
251
14. Ogata J, Feigin I: Arteriovenous communications in the human brain. J Neuropathol Exp Neurol 31:519-525, 1972 15. de Brux J-L, Subayi J-B, Pegis J-D, Pillet J: Retrograde cerebral perfusion: Anatomic study of the distribution of blood to the brain. Ann Thorac Surg 60:1294-1298, 1995 16. Dressler LR McKinney WM: Anatomic and pathophysiologic studies of the human internal jugular valve. Am J Surg 154:220-224, 1987 17. Pagano D, Boivin CM, Faroqui MH, Bonser RS: Retrograde perfusion through the superior vena cava perfuses the brain in human beings. J Thorac Cardiovasc Surg 111:270-272, 1996 18. Griepp RB, Juvonen T, Griepp EB, et al: Is retrograde cerebral perfusion an effective means of neural support during deep hypothermic circulatory arrest? Ann Thorac Surg 64:913-916, 1997 19. Midulla PS, Gandsas A, Sadeghi A, et al: Comparison of retrograde cerebral perfusion to antegrade cerebral perfusion and hypothermic circulatory arrest in a chronic porcine model. J Card Surg 9:560-575, 1994 20. Juvonen T, Weisz DJ, Wolfe D, et al: Can retrograde perfusion mitigate cerebral injury following particulate embolization? A study in a chronic porcine model. J Thorac Cardiovasc Surg (in press) 21. Yoshimnra N, Okada M, Ota T, Nohara H: Pharmacologic intervention for ischemic brain edema after retrograde cerebral perfusion. J Thorac Cardiovasc Surg 109:1173-1181, 1995 22. Usui A, Abe T, Murase M: Early clinical results of retrograde cerebral perfusion for aortic arch operations in Japan. Ann Thorac Surg 62:94-103, i996 23. Frazee J, Shiroishi M, Luo X, et al: A novel backdoor stroke therapy--Neuroperfusion. 22nd International Joint Conference on Stroke and Cerebral Circulation, February 8th, Anaheim, CA, 1997