Ann Thorac Surg 2000;70:1478-1482
© 2000 The Society of Thoracic Surgeons
Original articles: cardiovascular
Fundus microvascular flow monitoring during retrograde cerebral perfusion: an experimental study
Peiqing Dong, MDa,
Yulong Guan, MDa,
Jing Yang, MDa,
Meiling He,
Caihong Wan, MDa
a Beijing Anzhen Hospital, Beijing Capital Medical University, Beijing Heart, Lung and Blood Vessel Medical Institute, Beijing, People's Republic of China
Address reprint requests to Dr Dong, Extracorporeal Circulation Department, Beijing Heart, Lung and Blood Vessel Medical Institute, Beijing Anzhen Hospital, Beijing 100029, People’s Republic of China
e-mail: qsww{at}public.east.cn.net
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Abstract
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Background. Retrograde cerebral perfusion (RCP) through the superior vena cava was clinically introduced as a supportive technique to protect the brain during deep hypothermic circulatory arrest. This study searched for a direct monitor of cerebral blood flow to evaluate the effect of cerebral perfusion.
Methods. Retinal microvascular perfusions were studied in six piglets using fundus fluorescein angiography (FFA) and color Doppler sonography before cardiopulmonary bypass and retrograde cerebral perfusion during deep hypothermic circulatory arrest.
Results. FFA showed initial filling of the fundus venae in 2.5 minutes, and complete filling in 4.5 minutes with partial filling of the arteriae. Arteriae completely filled in 8 minutes, and all of the arteriae and venae filled from 15 to 17 minutes. Color Doppler sonography showed that flow signals were detected in all of the fundus vessels during RCP.
Conclusions. FFA and color Doppler sonography are direct and sensitive methods for observing cerebral blood flow and assessing the effect of cerebral perfusion.
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Introduction
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During surgical repair of the aortic arch, retrograde cerebral perfusion (RCP) through the superior vena cava is a simple and safe method to protect the brain during deep hypothermic circulation arrest. Although many authors have reported the use of RCP, controversy still exists as to whether brain tissue is perfused by RCP. This study was undertaken to observe fundus microvascular development and the status of blood flow for the assessment of cerebral perfusion by means of fundus fluorescein angiography (FFA) and color Doppler sonography.
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Material and methods
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The study was carried out with six healthy piglets, weighing 18 to 20 kg, supplied by the Beijing College of Agriculture. Animals received humane care in compliance with the Principles of Laboratory Animal Care formulated by the National Society for Medical Research, and the Guide for the Care and Use of Laboratory Animals by the National Academy of Sciences (National Institutes of Health, Publications 85–23; revised 1985). Anesthesia was induced with peritoneal injection of 3% pentobarbital sodium (1.5
2.0 ml/kg) and intravenous pancuronium (0.1 mg/kg) was used as a muscle relaxant. The anesthesia was maintained with intravenous fentanyl (10 µg/kg).
Fundus fluorescein angiography for normal control
The FFA normal control pictures were produced two days before the experiment. The porcine right pupil was dilated with atropine sulfate eye drops and was exposed with an eyelid retractor 5 minutes later. The retinal camera (NIKON 505, Nikon Corporation, Tokyo, Japan) was mounted at the head of the surgical table and after it was focused on the optic papilla, 3 ml of 20% sodium fluorescein was injected as a rapid bolus into the venae preaurilares. Ten seconds later, sequential retinal pictures were taken until retinal arteriae and venae developed homogeneously within 3 minutes.
Cardiopulmonary bypass and retrograde cerebral perfusion
After endotracheal intubation through tracheotomy, the animals were maintained on positive pressure ventilation with 100% oxygen. Appropriate catheters were positioned in the right carotid and jugular vein to allow sampling and pressure monitoring. The esophagus and rectum temperature probes were inserted. Through a median sternotomy, the ascending aorta was cannulated, two separated venous cannulas (22F), and vena caval tapes were applied with clamping of the azygos vein and the hemiazygos vein (Fig 1). Cardiopulmonary bypass (CPB) was established at a flow rate of 80100 ml/kg to maintain perfusion pressure at 6070 mm Hg. Cardiac arrest was induced by cold crystalloid cardioplegia through aortic root when the aorta was clamped at an esophageal temperature of 30°C. Then the animals were cooled to attain an esophagus temperature of 18°C and a rectal temperature of 20°C, and the CPB was discontinued. The shunt between the superior vena cava and the aorta was unclamped and RCP was begun (Fig 2). The retrograde flow rate was regulated to maintain a perfusion pressure of 25 mm Hg at 5.59.5 ml/kg per minute. Then 3 ml of 20% sodium fluorescein was injected as a rapid bolus into the superior vena cava and observation was made at the same time until the retinal arteriae and venae developed homogeneously. After 90 minutes of RCP, the animals were switched to normal CPB and rewarming was initiated. Cardiopulmonary bypass was ended 120 minutes after the start of rewarming.
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Fig 1. Diagram showing perfusion through aortic cannula, venous drainage from superior and inferior vena cava cannula. The shunt between aortic cannula and superior vena cava cannula was clamped during cardiopulmonary bypass. (AO = aorta; IVC = inferior vena cava; OX = oxygenator; SVC = superior vena cava.)
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Fig 2. The aortic cannula was clamped and the shunt between aortic and superior vena cava was opened during retrograde cerebral perfusion. Blood was perfused through superior vena cava (speckled), returned from cephalic artery (black). (AO = aorta; IVC = inferior vena cava; OX = oxygenator; SVC = superior vena cava.)
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Color doppler sonography examining
The central retinal artery (CRA), central retinal vein, ophthalmic artery, ophthalmic vein, common carotid artery, and common carotid vein were examined with the Acuson 128XP/10 color Doppler sonography (Acuson Corporation, Mountain View, CA) two days before the operation, just before circulation arrest, during RCP, 15 minutes after rewarming, and 45 minutes after rewarming. A transmitted Doppler frequency of 7.5 MHz and a wall filter setting of 50 Hz were utilized. The CRA was detected at about 2 mm posterior to the globe of optic nerve hyporeflective stripe, and ophthalmic artery at about 1525 mm posterior to the globe. The sample volume was adjusted to 23 mm and the angle between vessels and sound beam were kept below 20 degrees. The flow velocity (frequency) spectrum of arteriae and venae was recorded to assess diameter of vessels, speed of blood flow, pulsation index and resist index. The unit of blood flow speed was cm/sec.
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Results
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Fundus fluorescein angiography development
The baseline fundus color photography before operation showed that the porcine fundus vessels included the superior nasal, inferior nasal, superior temporal, inferior temporal arteriole, and venule (Fig 3) , which were similar to that seen in the atlas of human fundus. The FFA from two days before the operation showed artertiae developed at 13 seconds initially and venae developed at 25 seconds later. Until 45 seconds, the fluorescein intensity of arteriae attenuated and that of venae maintained unchanged (Figs 4A and B).
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Fig 3. Fundus photography before operation shows the branches of the central retinal artery and central retinal vein
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Fig 4. Fluorescein angiogram of the animals (A) 13 seconds and (B) 24 seconds after a single injection of 3 ml of 20% sodium fluorescein. (C) After the initiation of retrograde cerebral perfusion, some branches of veins developed in 2.5 minutes. (D) All branches of veins and partial branches of arteries developed in 4.5 minutes. (E) All veins and arteries developed in 15 minutes. (F) The fluorescein angiogram in 15 minutes also showed veins and arteries clearly.
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The FFA of the RCP showed initial development of the venae in 2.5 minutes and complete development in 4.5 minutes with partial development of the arteriae; the latter developed completely around 8 minutes. All of the arteriae and venae developed from 15 to 17 minutes (Figs 4C, D and E). Figure 4F showed the fluorescein development. During the experiment, the inferior vena cava was clamped transiently and the speed of blood flow became slow. Recovery of the blood speed occurred when the inferior vena cava was unclamped.
Color doppler sonography examining
The flow velocity spectrums showed normal waveform of CRA and ophthalmic artery characterized by three peaks and two valleys. The peaks of the flow velocity spectrums dropped while the temperature decreased. The flow signal can be detected in all of the fundus vessels (Figs 5A and B). The peaks of flow velocity spectrums gradually elevated after rewarming (Table 1).
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Fig 5. The flow signal can be detected in (A) central retinal vein and (B) central retinal artery after the initiation of retrograde cerebral perfusion.
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Comment
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Since the first report by Ueda and colleagues [1] in 1990 on the continuous RCP to protect the brain during aortic arch operations, the progressive research on RCP had been both rapid and in depth. As a method for the protection of the brain during deep hypothermic circulation arrest, RCP has the advantages of safety and simplicity easily accepted by the surgeons. Sun and associates [2] in China for the first time in 1994 reported the use of RCP, the period of which lasted for 2781 minutes. All the patients returned to consciousness within four hours after the operation and there were no detectable neurologic defects postoperatively. RCP was used more extensively since 1995. A large number of clinical studies have demonstrated that RCP has the effect of cerebral protection and can prolong safety duration of circulation arrest. Sasaguri and associates [3] reported the longest time of RCP of 135 minutes and encountered no neurologic complications related to the procedure after surgery; however, some authors were suspicious about RCP being able to provide effective cerebral perfusion. Boeckxstaens and Flameng [4] in an experimental study using baboon, found significant cerebral blood flow as not being able to be detected by microsphere methods and less than 1% of the RCP inflow returned to the aortic arch during hypothermic RCP. Ye and associates [5] reported that only a small amount of blood flow returned from the innominate artery with India ink as a marker. However, a number of published papers and our initial studies have demonstrated that 20% of RCP inflow returned to the aorta. Dong [6] reported the use of technetium 99-labeled perfusion agent (ethyl cysteinate dimer [99mTc-ECD]) during RCP. Cerebral perfusion images showed homogeneous perfusion of cerebrum, cerebellum, and medulla oblongata in 3 minutes after the start of RCP. Pagano and associates [7] reported 3 patients in which technetium 99-labeled perfusion agent (d,l-hexamethyl propylene amine oxime [99mTc-HMPAO]) was used during RCP to obtain a perfusion image with a portable gamma camera in the operating theater. Time activity curves showed homogeneous perfusion of both cerebral hemispheres in all patients during RCP. Although all of the previous image observations can assess the effect of RCP in animal experiments, it is of more importance to observe the cerebral vessel perfusion directly during RCP.
The retina lying in the rear of the eye, similar to the other parts of the central nervous system, originates from the neurocanal. Many of its functions and characteristics show that the retina is a part of the brain. The retinal vessels stem from cerebral circulation. The internal carotid artery is the source of CRA and the omental ciliary artery, while the central retinal vein joins into the cavernous sinus and pterygoid venous plexus. Being the only vessels of cerebral circulation that can be observed directly through fundus, fundus vessels are "windows " for the observation of cerebral microcirculation.
Blauth and associates [8] observed microemboli in patients undergoing CPB by means of FFA. With retinal photography and a vertically mounted retinal camera focused on the macula of the eye, a very high-quality definition of the retinal microcirculation can be obtained during cardiac surgery. The results showed truncation of a vessel and loss of retinal capillary perfusion, as well as other defects of other areas in the retina both centrally and peripherally around the macula. In our study, the fundus vessels were selected as the object of observation, and the CRA and central retinal vein were studied by FFA. It was found that the porcine fundus vessels were similar to the fundus atlas of human beings. The development of FFA during RCP showed blood perfusion existed in the central retinal vein in 2.5 minutes and in the CRA in 4.5 minutes. This experiment fully demonstrated that RCP is able to perfuse the cerebral tissues.
During the experiment azygos and hemiazygos were ligated because there was a difference between human being and animals, such as pigs. In the preliminary test, it was found out that there were 25%40% pigs whose azygos and hemiazygos directly returned into right atrium. If they weren’t ligated, retrograde blood would return back to the right atrium and not to the brain. Our experiment also indicated that clamping the inferior vena cava during RCP resulted in slowing down the blood flow of the central retinal vein and the speed of blood flow recovered after declamping. It was possible that 80% of the retrograde flow returned from the inferior vena cava, and that all the blood returned to the aorta while the inferior vena cava was clamped and the resistance of blood flow might increase, resulting in cerebral edema. Apparently this experiment supports the idea that the inferior vena cava should be unclamped during RCP, a conclusion identical with Juvonen and associates [9].
Deverall and associates [10] detected the passage of microemboli in the middle cerebral artery during CPB by transcranial Doppler; also color Doppler sonography was used extensively to observe the change of fundus vessels (which in our study was used for the assessment of the fundus blood flow). The image of the arteriae and the venae showed well and the fundus arteriae showed the undulated form of three peaks and two valleys similar to that visualized in the human’s fundus arteriae. Definite blood flow signals were detected in all vessels during RCP, which demonstrated the latter being able to perfuse cerebral tissue equally. It was found that following the start of CPB, the speed of blood flow of fundus vessels slowed down along with the dropping of temperature, and the speed of blood flow recovered progressively when rewarming was in progress. This conformed to the fact that temperature has a significant effect on micrangium perfusion.
The methods of cerebral monitoring during CPB and RCP included electroencephalography, jugular venous bulb saturation (SjO2), near-infrared spectroscopy, transcranial Doppler, isotope scanning, etc. As demonstrated in our experiment with FFA and color Doppler sonography, RCP has a definite cerebral protective effect. In comparison with other methods of cerebral monitoring, FFA and color Doppler sonography have the characteristics of forthrightness, noninvasiveness, and sensitivity, being able to carry out continuous observations. These methods are valuable for the evaluation of cerebral perfusion especially for some special clinical situations.
In conclusion, FFA and color Doppler sonography are direct and sensitive methods to observe cerebral blood flow and to assess the effect of cerebral perfusion.
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References
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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 (Torino) 1990;31:553-558.[Medline]
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Sun Y.Q., Dong P.Q., Yang C.R., et al. Application of retrograde perfusion through superior vena cava during deep hypothermic circulatory arrest in operation of aortic aneurysm. Chinese J Thorac Cardiovasc Surg 1994;10:25-27.
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Sasaguri S., Yamamoto S., Hosoda Y., et al. What is the safe time limit for retrograde cerebral perfusion with hypothermic circulatory arrest in aortic surgery?. J Cardiovasc Surg (Torino) 1996;37:441-444.[Medline]
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Boeckxstaens C.J., Flameng W.J. Retrograde cerebral perfusion does not perfuse the brain in nonhuman primates. Ann Thorac Surg 1995;60:319-327.[Abstract/Free Full Text]
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Ye J., Yang L., Bigio D., et al. Retrograde cerebral perfusion provides limited distribution of blood to the brain. J Thorac Cardiovasc Surg 1997;114:660-665.[Abstract/Free Full Text]
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Dong P.Q. The cerebral protection in great vessels surgery. In: Hu X.Q., ed. The cardiovascular anesthesia and cardiopulmonary bypass. Beijing, China: The People’s Medical Publishing House, 1997:489-498.
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Pagano D., Boivin C.M., Faroqui M.H., et al. Retrograde perfusion through the superior vena cava perfuses the brain in human beings. J Thorac Cardiovasc Surg 1996;111:270-272.[Free Full Text]
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Blauth C., Arnold J., Kohner E.M., et al. Retinal microembolism during cardiopulmonary bypass demonstrated by fluorescein angiograhy. Lancet 1986;2:837-839.[Medline]
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Juvonen T., Zhang N., Wolfe D., et al. Retrograde cerebral perfusion enhance cerebral protection during prolonged hypothermic circulatory arrest. Ann Thorac Surg 1998;66:38-50.[Abstract/Free Full Text]
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Deverall P.B., Padayachee T.S., Parsons S., et al. Ultrasound detection of micro-emboli in the middle cerebral artery during cardiopulmonary bypass surgery. Eur J Cardiothorac Surg 1988;2:256-260.[Abstract]
Accepted for publication April 26, 2000.
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Abstract
Introduction
