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Three Part Question

In patients having [aortic arch surgery] can [antegrade cerebral perfusion (ACP) or retrograde cerebral perfusion (RCP)] reduce [neurological injury or mortality]?

Clinical Scenario

You are about to perform surgery on a 65-year-old gentleman with an acute aortic dissection. He was admitted through the accident and emergency department with acute chest pain. His chest X-ray showed a widened mediastinum and he underwent a computerised tomography scan of his chest which confirmed the diagnosis of a type 1 aortic dissection. He is a smoker and has a previous history of a transient ischaemic attack. A carotid Doppler scan performed at that time showed mild to moderate bilateral internal carotid artery disease and surgery was not indicated. The patient is stable but surgery is inevitable to save this patient's life. You plan your surgery and you think about the best method of protecting his brain during the circulatory arrest period. You consult two colleagues about the optimal method of cerebral protection. One surgeon tells you that retrograde cerebral perfusion is a quick and easy way to ensure good cerebral protection. A second surgeon tells you that there is no evidence that this works at all and none of the perfusate actually gets to the brain with this method. He tells you that there is no substitute for quick stitching! You elect to look up the evidence.

Search Strategy

Medline 1966-Dec 2003 using the OVID interface
[exp aortic surgery/ OR aortic arch surgery/OR aortic dissection/ OR aortic aneurysm] AND [exp cerebral protection/ OR antegrade cerebral protection OR selective cerebral perfusion OR retrograde cerebral protection] AND [expmortality/ OR exp survival/ OR Survival.af/ OR exp stroke/ OR neurological injury/ OR transient ischaemic attack] LIMIT to English language.

Search Outcome

Altogether 408 papers were found with a further 3 papers found by checking the references of relevant papers. Relevant papers numbered 26 of which 4 were out of scope and 9 were rejected on the basis of poor methodology. Only 16 papers were reviewed in full. Both clinical studeis and animal experimental studies that were felt to be of relevance are listed in the table. In terms of clinical studies several early studies supporting the efficacy of retrograde cerebral perfusion were found which were rejected because they were retrospective cohort studies with no objective assessment of neurological injury.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Okita et al 2001 Japan	60 patients undergoing non emergency total arch replacement with deep hypothermic circulatory arrest SCP group: selective antegrade cerebral perfusion (30 pts). Axillary artery or direct brachiocephalic artery balloon tipped cannulation. Perfusion at 300-500ml/min RCP group: retrograde cerebral perfusion (30 pts) continuous, maintaining jugular pressure of 15-20mmHg Patients cooled to 18 degrees centigrade Pre-and post op CT scans and neurological examinations performed	PRCT (Level 2b)	Mortality	RCP group 2/30 deaths (7%). SCP group 2/30 deaths (7%)	No sample size calculations Operation time, Extracorporeal Circulation, and Cerebral Perfusion Times were all significantly longer in the ACP group. (operation time 467 vs 365 mins) Patients were cooled more in the RCP group (18 vs 22 degrees) p=0.04 Flawed randomization technique, as method was simply alternated as patients presented. This introduces inclusion bias
			New strokes	RCP group 1 stoke. SCP group 2 new strokes p=0.6
			Transient Ischaemic Brain Function.	RCP group 10/30 pts (33%). SCP group 4/30 pts, (13%) p = 0.05
			S-100b values at 48 hours .	RCP group 0.36+/-0.45 mcg/l. SCP group 0.46+/-0.40 mcg/l, p = 0.7
			Cognitive Impairment	There were no intergroup differences in the scores of memory decline orientation or intellectual function
Taroue et al 1999 Japan	32 consecutive patients undergoing elective surgical repair of an aortic aneurysm involving the aortic arch. Retrograde cerebral perfusion via SVC , with SVC pressure of 15-25mmHg (n = 15) Selective antegrade cerebral perfusion via 3 balloon catheters to 3 arch vessels, at 500ml/min. (n = 17 pts) Patients cooled to 15 degrees centigrade Continuous measurement of middle cerebral artery blood flow velocities was performed by transcranial Doppler technique	PRCT (level 2b)	Middle cerebral artery (MCA) blood flow velocities.	RCP group: only 3 patients had any detectable MCA flow. Flow was 6%, 20% and 21% of MCA flow velocities before CPB. SCP group: detectable flow in 16 patients. Mean velocity was 43.8% +/- 35.8% in the antegrade cerebral perfusion group. P=0.0001. The increase in middle cerebral artery blood flow velocities after RCP was significantly greater than that after selective cerebral perfusion indicating possible reactive hyperaemia	Randomization method not described RCP was through the SVC rather than through the internal jugular vein and therefore allowed a significant degree of shunting Duration of RCP was mean 38mins vs 71mins SCP, p=0.0047, Tanoue et al now use RCP rather than SCP in their practise despite this study
			Mortality	SCP: 1 death due to bleeding. RCP: 2 deaths from cerebral infarction and one survived stroke
Higami et al 1999 Japan	92 consecutive patients undergoing non emergency arch surgery SCP group: Non-clamping Selective Cerebral Perfusion (SCP) with 3 balloon catheters to arch vessels at 300-350 ml/min and pressure of 30mmHg ( n =52) RCP group: SVC cannulation and jugular venous pressure maintained at 20mmHg and flow of 200 to 350ml/min ( n= 40 ), or via femoral artery with trendelenburg positioning. Patients cooled to 20 degrees centigrade Near-infrared optical spectroscopy measurements of regional cerebrovascular oxygen saturations compared between the two methods	Retrospective Cohort study (level 4)	Changes in regional cerebrovascular oxygen saturation.	At the end of the brain protection strategy rSO2 was 57.4% +/- 12.2% for RCP and 71.7% +/- 6.9% for SCP. Decreases during the interval from initiation to conclusion of brain protection were 24.4% and 3.7% respectively.	Theere was no randomization of the two techniques There were significant differences between the 2 groups in terms of numbers of patients having reconstruction of the arch, cerebral perfusion time, CPB time and minimum temperature Perfusion time was mean 38 mins for RCP and 103mins for SCP.
			Mortality/morbidity	SCP group 3 small cerebral emboli. RCP group 1 patient had cerebral infarction
Moon et al 2000 USA	72 consecutive patients undergoing aortic arch procedures using hypothermic circulatory arrest.(HCA) 36 patients had HCA alone. 36 patients had HCA and supplemental RCP to SVC with Innominate vein pressure of 20-25mmHg and flow 300-500ml/min Patients cooled to 18 degrees centigrade	Retrospective Cohort study (level 4)	Mortality	HCA Alone 3/36 pts (8%). HCA plus RCP 4/36 pts (11%_ p > 0.73	Underpowered to exclude a clinical difference between these two groups The groups were similar in age, emergent status, and cardiopulmonary bypass time (p > 0.08), but arrest time was higher with RCP (40 +/- 15 minutes versus 29 +/- 14 minutes; p < 0.001).
			cerebrovascular accident.	HCA Alone 4 CVAs and 4 TIAs. HCA plus RCP 2 CVAs and 6 TIAs p=NS
Di Eusianio et al 2003 Netherlands	289 patients undergoing ascending hemiarch replacement 161 patients who underwent ascending aortic arch surgery with use of antegrade selective cerebral perfusion using coronary sinus perfusion cannulas inserted into innominate and left coronary arteries, and moderate hypothermic circulatory arrest to 22-26 degrees centigrade 128 patients who underwent ascending aortic arch surgery with use of deep hypothermic circulatory arrest alone.(to 16 degrees centigrade)	Retrospective Cohort study (level 4)	Mortality	ACP + HCA 16/161 pts (9.9 %). HCA alone 17/128pts (13.3 %). p = 0.375	Retrospective study. More extended aortic tissue replacements and larger numbers of aortic root repairs were performed in the ACP group.
			Neurologic Dysfunction	ACP + HCA = 11/161pts (7.6%). HCA alone 16/128pts (12.5%). p = 0.075
Hagl et al 2001 USA	717 patients who survived ascending aorta-aortic arch operations through a median sternotomy since 1986 were examined for factors influencing stroke. HCA alone, with cooling to 10-13 degrees centigrade ( n = 588) RCP via SVC using pressure of 15-20mmHg ( n = 43) ACP via a haemashield graft anastomosed to island of arch vessels. This island was later anastomosed to arch graft ( n = 86) Temporary neurologic dysfunction assessed in all patients who survived the operation without stroke since 1993.	Retrospective cohort study (level 4)	Stroke and transient neurological dysfunction.	In patients with total cerebral protection times > 40 and < 80 minutes method of cerebral protection did not influence occurrence of stroke. ACP resulted in a significant reduction in incidence of temporary neurologic dysfunction (P =.05; odds ratio, 0.3).	Non randomized retrospective study using differing surgeons, types of pathology and evolving surgical techniques
Matalanis et al 2003 Australia	62 patients having aortic arch repair. Hypothermic Arrest (HCA) with cooling to 19 degrees centigrade (14 pts) RCP group: HCA and RCP using SVC cannulation , pressure of 20-25mmHg and flow 200-300ml/min ( 23 pts) ACP group: HCA with ACP using occluding balloon catheter with radial pressure maintained to 40-60mmHg (25 pts)	Retrospective Cohort study (level 4)	Hospital mortality and stroke.	HCA group 1 death, 0 CVAs. RCP group 0 deaths, 1 CVA. ACP group 4 deaths, 3 CVAs	Small study. No measure of subtle neurological differences between patient groups. Retrospective. Groups were markedly dissimilar Antegrade Cerebral Perfusion patients had more extensive repairs and a longer total brain exclusion time.
			Total brain exclusion time (TBET).	TBET was significantly longer in ACP (HCA, 25.2+/-12.0 min; ACP, 61.8+/-44.1 min; RCP, 36.4+/-20.5 min; p=0.023).
			Actuarial survival rate.	The actuarial survival rate was 88.7% at five years (DHA, 85.7%; ACP, 80.0%; RCP, 100%; no significant difference)
Sinatra et al 2001 Italy	85 consecutive patients operated on for acute type A aortic dissection over a 6-year period HCA group (n=44) Circulatory arrest with cooling to 17 degrees centigrade ACP group (23pts) Innominate artery cannulated directly , perfused at 250-700ml/min. RCP group SVC perfused to 20-25mmHg with flow 200-700ml/min	Retrospective Cohort study (level 4).	Mortality	Overall mortality rate was25.9% (22 of 85 patients). Multiple logistic regression analysis showed that lack of cerebral perfusion (p = 0.021) and postoperative renal failure (p = 0.006) were the best predictors for hospital death. Hospital mortality was 13% (3 of 23 patients) and 16.7% (3 of 18 patients) in the antegrade and retrograde cerebral perfusion groups (p=NS).	Outcomes are confounded by improvements in healthcare with time. Differences between groups were not presented in detail to allow for comparison.
			Neurological deficit	21 patients (24.7%) experienced neurologic accidents. Neurologic deficit was 13% (3 of 23 patients) in the antegrade and 11.1% (2 of 18 patients) in the retrograde groups.
Filgueiras et al 1995 Canada	28 pigs divided into five groups. Anaesthesia n = 5 Hypothermic CPB n = 5 HCA alone n = 6 HCA + ACP n = 6 ACP via the carotid arteries at a blood flow rate of 180 to 200 ml.min-1 during circulatory arrest at 15 degrees HCA + RCP = 6 perfusion through the superior vena cava at a flow rate of 300 to 500 ml.min-1 during circulatory arrest at 15 degrees C To evaluate the effect of HCA on brain metabolism 31P-magnetic resonance spectroscopy was used to monitor brain metabolites in pigs during 2 hours of ischemia and 1 hour of reperfusion.	Experimental study	Circulatory arrest intracellular pH at 110 mins	HCA group 6.3 ± 0.1. ACP group 7.2 ± 0.1. RCP group 6.4 ± 0.1	Retrograde perfusion through the SVC allows some blood flow to be diverted to the upper limbs and does not give a model of uniform retrograde cerebral blood flow. Study was carried out in pigs subjected to a 2 hour arrest period which is seldom used clinically.
			Reperfusion pH after arrest	HCA group 6.2 ± 0.7. ACP group 7.1 ± 0.1. RCP group 7.1 ± 0.1
			Inorganic Phosphates (Pi)	HCA group Pi increased during arrest and the high energy phosphate levels decreased gradually. During recovery Pi remained higher than in the control groups. ACP group peak high energy phosphates were maintained at control values during the entire experiment and Pi remained very low. RCP group, Pi increased and high-energy phosphate levels decreased during circulatory arrest. During recovery the Pi levels decreased and the ATP and PCr peaks returned to control values.
Duebener et al 2003 USA	12 pigs undergoing Hyopthermic circulatory arrest Deep Hypothermic Circulatory Arrest (HCA) group (n=6 pigs) 40 mins of cooling to 15 degrees centigrade, 45 mins of arrest RCP group (n=6 pigs) SVC perfusion of 30ml/kg/min, jugular bulb pressure of 30mmHg. Plasma was labelled with fluorescein-isothiocyanate-dextran for assessing microvascular diameter and functional capillary density (FCD). Cerebral tissue oxygenation was determined by nicotinamide adenine dinucleotide hydrogen (NADH) autofluorescence, which increases during tissue ischemia.	Experimental study	Functional Capillary Density (FCD)	HCA group FCD did not significantly change from base line 97% +/- 14%. RCP group FCD decreased to 2% +/- 2% of base line values (p < 0.001). There was no evidence of significant capillary blood flow during retrograde cerebral perfusion.	Non human model of cerebral perfusion. No comparison of the effects of antegrade cerebral perfusion in the same model.
			Microvascular diameter of cerebral arterioles	The microvascular diameter of cerebral arterioles that were slowly perfused significantly decreased to 27% +/- 6% of base line levels during RCP.
			Cerebral Tissue Oxygenation.	NADH fluorescence progressively and significantly increased during RCP, indicating poorer tissue oxygenation.
			Evidence of Brain Oedema.	At the end of retrograde cerebral perfusion there was macroscopic evidence of significant brain edema.
Katz et al 1999 Israel	24 rabbits injected with 5mCi of technetium-99 macroaggregated albumin, a tracer trapped in the capillaries Group I (n=6) normothermic with tracer injected into ascending aorta Group II (n=6) normothermic, underwent cannulation of the SVC with exsanguination through aorta, and injection of tracer into SVC, which was proximally occluded Group III (n=6) cooled to 25 degrees C. The animal was exsanguinated through the ascending aorta and tracer was injected into the SVC. Group IV (n=6) cooled to 25 degrees C. The animal was exsanguinated through the ascending aorta and tracer was injected into the SVC. Group V (n=3) exsanguinated through the ascending aorta and a retrograde venogram of the SVC was performed Scintigraphy of groups I to IV was carried out on a digital gamma camera. Brain trapping of tracer was graded from 0 to 5, with 0 being no tracer in the brain and 5 being dominant tracer in the brain	Experimental Study	Degree of brain trapping of technetium-99 macroaggregated albumin. Indicating flow into the cerebral capillary system	Tracer trapping in the brain showed group I, 3.67+/-0.82; group II, 0; group III, 4.67+/-0.41; group IV, 0.17+/-0.41 (p<0.0001). Retrograde venogram of the SVC showed flow into the cerebral veins. Retrograde flow through the SVC reaches the cerebral venous system but does not go through the capillary system.	During retrograde injections in this study, methods were not applied to reduce venovenous shunting to the lower body, although it was demonstrated that most of the flow did go to the head. Scintigram interpretation was subject to error in grading.
Sakurada et al 1996 Japan	19 dogs examined for the effects of cerebral protection strategies on cerebral function in terms of somatosensory evoked potentials RCP group with cannulae in both maxillary veins with vena cavae clamped and sagital sinus pressure maintained at 25mmHg(n=8) SCP group, with a cannula in the aortic arch with prox and distal aorta clamped (n=6) HCA with cooling down to 20 degrees centigrade (n=5)	Experimental study	Somtosensory evoked potentials (SEP)	Somatosensory evoked potentials stopped when HCA or RCP were commenced and failed to recover completely. In the SCP group, the SEP recovered in all cases	Animal experimental model No randomisation Small numbers
			Changes in cerebral tissue blood flow	During cerebral perfusion and circulatory arrest, the blood flow showed 2.2% +/- 1.0% of the preoperative value I the RCP group, 42.5% +/- 22.1% in the SCP group, and 1.0% +/- 0.6% in the HCA group
			Changes in cerebral metabolic rate for oxygen	During cerebral perfusion and circulatory arrest, the rate was 3.3% +/- 2.3% of the preoperative value in the RCP group and 31.8% +/- 14.9% in the SCP group
			cerebral tissue ATP	cerebral tissue ATP content was 0.74 +/-0.13 umol/g in the RCP group, 1.01 +/- 0.75 in the SCP group, and 0.60% in the HCA group, and no significant difference was observed
Midulla et al 1994 USA	4 groups of 6 pigs (20 to 30 kg) randomly assigned to undergo 90 minutes of RCP, ACP, HCA, or HCA with heads packed in ice (HCA-HP) at an esophageal temperature of 20 degrees C. (90 minutes was used to exceed acknowledged safe limits for HCA in order to induce neurological damage) RCP group SVC cannulation and infusion to maintain saggital sinus pressure of 30mmHg ACP group cannula introduced into arch with proximal and distal aortic clamping and perfusion pressure of 50mmHg	Experimental Study	Mean Behavioural Score	Mean behavioural score was lower in the HCA group than in the other three groups at 7 days (HCA 5.8+/-1.1; RCP 8.5+/-0.2; ACP 9.0+/-0.0; HCA-HP 8.5+/-0.2, p<0.05)	Comparison of RCP to HCA and antegrade cerebral perfusion (ACP) deliberately exceeding "safe limits" Non human model of cerebral perfusion
			EEG	Recovery of EEG was better in the ACP group than in all the others, but the RCP group had faster EEG recovery than HCA alone, although not better than HCP-HP (HCA 15+/-4; RCP 27+/-3; ACP 78+/-5; HCA-HP 19+/-3; p<0.001)
Neri et al 2004, Italy and France	67 patients undergoing elective aortic arch procedures Group 1 HCA alone n=25 Group 2 HCA+ACP n=25 Group 3 HCA+RCP n=19 Patients were tested to see what impact different cerebral protection methods had on cerebral autoregulation of blood flow Using an autoregulator index (ARI) of 3 patients were divided into those with intact autoregulation and those impaired autoregulation Adequate ARI was taken as greater than 3	Prospective non-randomized cohort study (level 2b)	ARI	Group 1 ARI>3=1Group 2 ARI>3=25Group 3 ARI>3=0P<0.001The data demonstrate that patients who underwent surgery with HCA alone or RCP had impaired cerebral autoregulation	Non-randomized Surgeon preference determined cerebral protection technique Non-heterogeneous groups
			Mortality	None
			Neuro complications	No ACP n=11 (100%) P=0.001 HCA alone n=7 (63.3%) P=0.4

Comment(s)

Two prospective randomized controlled trials (PRCTs) comparing antegrade and retrograde cerebral protection were found (Okita, Tanoue). These both favoured antegrade cerebral protection over retrograde cerebral protection with varying strengths of evidence. Okita et al performed a PRCT comparing retrograde cerebral perfusion (RCP) against selective antegrade cerebral perfusion (SCP) with 30 patients in each group. Due to the small numbers in each cohort there were no statistically significant outcomes in terms of mortality, stroke, S-100b values or cognitive impairment. However transient brain dysfunction was higher in the RCP group, with 10 patients in the RCP group compared to only 4 in the SCP group suffering dysfunction. Tanoue et al performed PRCT comparing middle cerebral artery blood flow velocities in 32 patients having elective repair of an aortic arch aneurysm and demonstrated much better flow in the middle cerebral artery with the SCP strategy than with RCP. Despite this they continue to use RCP in their daily practise. Neri et al assessed cerebral autoregulation of blood flow in elective patients having aortic arch surgery and took this as a measure of cerebral protection. In this non-randomized prospective study they were able to demonstrate that there is a benefit to the use of ACP, however, the observational nature of this study where different surgeons utilized different techniques may have introduced bias. Among the cohort studies, Higami et al demonstrated significantly better cerebrovascular oxygen saturation in the SCP group when compared to the RCP group with the use of near infrared spectroscopy in a retrospective study of 92 patients. Moon et al could not demonstrate any advantage of retrograde cerebral protection over hypothermic circulatory arrest alone in terms of mortality or morbidity in a cohort of 72 patients although the study was possibly too small to definitively exclude a difference. Di Eusiano et al could not demonstrate a clinical benefit with the use of antegrade cerebral perfusion compared to hypothermic circulatory arrest alone when they retrospectively reviewed 289 patients. Hagl et al demonstrated the benefits of ACP over RCP in terms of transient neurological dysfunction but this did not translate into a significant difference in terms of mortality or permanent neurological dysfunction. Matalanis et al also failed to illustrate a clinically significant difference between groups. Sinatra et al identified lack of cerebral protection as an independent risk factor over HCA alone in a cohort study of 85 patients undergoing Type A dissection, but could not distinguish an advantage of ACP over RCP. For evidence found in experimental animal studies (Filgueiras, Duebener, Sakurada, Katz and Midulla), Filgueiras et al demonstrated improved cerebral pH, and high energy phosphate levels during ACP. Duebener et al found no functional cerebral capillary blood flow on retrograde perfusion of the brains of 6 pigs. Sakurada et al demonstrated that antegrade perfusion improved cerebral evoked potentials, blood flow and metabolism compared to retrograde perfusion in 19 dogs. Katz et al demonstrated that in a rabbit model retrograde perfusion of the brain does not perfuse the cerebral capillary system. Midulla et al in their porcine model found that less than 5% of blood delivered retrograde via the SVC system returns via the aortic cannula. Most of the blood went from the SVC via venous collaterals to the IVC, despite ligation of the azygous vein. However behavioural scores in pigs undergoing RCP were better than HCA alone. Cerebral damage has been hypothesised to be caused by either inadequate cerebral protection or embolic events in these studies. Although physiological cerebral blood flow has not been demonstrated in any of the studies using retrograde perfusion, it is possible that some of the demonstrated clinical benefits of RCP may be due to sustained cerebral cooling or 'wast out' of embolic material. ACP has been shown to give physiological flow and improved metabolic effects, however authors report disadvantages including technical complexity, reduced surgical visibility, and manipulation of the aorta and aortic arch vessels, especially in cases of acute dissection or atherosclerotic aortic arch aneurysm.

Clinical Bottom Line

Antegrade cerebral perfusion is a better strategy than retrograde cerebral perfusion in aortic arch procedures requiring hypothermic circulatory arrest. This is demonstrated in a limited number of prospective randomized controlled clinical studies which have involved small numbers of patients and in cohort studies. The evidence from experimental animal models is more convincing in terms of explaining the benefits of antegrade cerebral perfusion.

References

1. Okita Y, Minatoya K, Tagusari O, Ando M, Nagatsuka K, Kitamura S. Prospective comparative study of brain protection in total aortic arch replacement: deep hypothermic circulatory arrest with retrograde cerebral perfusion or selective antegrade cerebral perfusion. Ann Thorac Surg 2001;72(1):72-9.
2. Tanoue Y, Tominaga R, Ochiai Y, Fukae K, Morita S, Kawachi Y, Yasui H. Comparative study of retrograde and selective cerebral perfusion with transcranial Doppler. Thorac Surg 1999;67(3):672-5.
3. Higami T, Kozawa S, Asada T, Obo H, Gan K, Iwahashi K, Nohara H. Retrograde cerebral perfusion versus selective cerebral perfusion as evaluated by cerebral oxygen saturation during aortic arch reconstruction. Ann Thorac Surg 1999;67(4):1091-6.
4. Moon MR, Sundt TM 3rd. Influence of retrograde cerebral perfusion during aortic arch procedures. Ann Thorac Surg 2002;74(2):426-31.
5. Di Eusianio M, Wesselink RMJ, Morshuis WJ, Dossche KM, Schepens MA. Deep Hypothermic circulatory arrest and antegrade selective cerebral perfusion during ascending aorta-hemiarch replacement : A retrospective comparative study. Journal of Thoracic and Cardiovascular Surgery 2003;125(4):849-854.
6. Hagl C, Ergin MA, Galla JD, Lansman SL, McCullough JN, Spielvogel D, Sfeir P, Bodian CA, Griepp RB. Neurologic outcome after ascending aorta-aortic arch operations: effect of brain protection technique in high-risk patients. J Thorac Cardiovasc Surg 2001;121(6):1107-21.
7. Matalanis G, Hata M, Buxton BF. A retrospective comparative study of deep hypothermic circulatory arrest, retrograde, and antegrade cerebral perfusion in aortic arch surgery. Ann Thorac Cardiovasc Surg 2003;9(3):174-9.
8. Sinatra R, Melina G, Pulitani I, Fiorani B, Ruvolo G, Marino B. Emergency operation for acute type A aortic dissection: neurologic complications and early mortality. Ann Thorac Surg 2001;71(1):33-8.
9. Filgueiras CL, Winsborrow B, Ye J, Scott J, Aronov A, Kozlowski P, Shabnavard L, Summers R, Saunders JK, Deslauriers R, et al. A 31p-magnetic resonance study of antegrade and retrograde cerebral perfusion during aortic arch surgery in pigs. J Thorac Cardiovasc Surg 1995;110(1):55-62.
10. Duebener LF, Hagino I, Schmitt K, Sakamoto T, Stamm C, Zurakowski D, Schafers HJ, Jonas RA. Direct visualization of minimal cerebral capillary flow during retrograde cerebral perfusion: an intravital fluorescence microscopy study in pigs. Ann Thorac Surg 2003;75(4):1288-93.
11. Katz MG, Khazin V, Steinmetz A, Sverdlov M, Rabin A, Chamovitz D, Schachner A, Cohen AJ. Distribution of cerebral flow using retrograde versus antegrade cerebral perfusion. Ann Thorac Surg 1999;67(4):1065-9.
12. Sakurada T, Kazui T, Tanaka H, Komatsu S. Comparative experimental study of cerebral protection during aortic arch reconstruction. Ann Thorac Surg 1996;61(5):1348-54.
13. Midulla PS, Gandsas A, Sadeghi AM, Mezrow CK, Yerlioglu ME, Wang W, Wolfe D, Ergin MA, Griepp RB. Comparison of retrograde cerebral perfusion to antegrade cerebral perfusion and hypothermic circulatory arrest in a chronic porcine model. J Card Surg 1994;9(5):560-74.
14. Higami T, Kozawa S, Asada T, Obo H, Gan K, Iwahashi K, Nohara H. Retrograde cerebral perfusion versus selective cerebral perfusion as evaluated by cerebral oxygen saturation during aortic arch reconstruction. Ann Thorac Surg 1999;67(4):1091–1096.