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Ann Thorac Surg 2002;73:198-202
© 2002 The Society of Thoracic Surgeons

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Original article: cardiovascular

Profound reduction in brain embolization using an endoaortic baffle during bypass in swine

^a Department of Anesthesiology, Mayo Foundation and Mayo Clinic, Rochester, MN, USA
^b Department of Surgery, Division of Cardiovascular Surgery, Mayo Foundation and Mayo Clinic, Rochester, Minnesota 55905, USA

Accepted for publication September 5, 2001.

* Address reprint requests to Dr Cook, Department of Anesthesiology, 200 First St SW, Rochester, MN 55905, USA
e-mail: cook.david{at}mayo.edu

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Background. Cerebral embolization during cardiopulmonary bypass is an important cause of neurologic injury. This study determined whether an endoaortic baffle catheter (Cardeon Cobra Catheter; Cardeon Corporation, Cupertino, CA) could substantially reduce cerebral embolization in a swine cardiopulmonary bypass model.

Methods. Sixteen 60 kg pigs underwent cardiopulmonary bypass; 8 animals with the Cobra baffle (Cardeon Corporation, Cupertino, CA) deployed, and 8 with the same cannula without baffle deployment. The animals were embolized with 72,000 fluorescent microspheres (97 to 100 µm) at normothermia. At the end of the experiment, the brains were removed and microspheres were isolated from eight regions.

Results. During embolization, the two groups were equivalent with regard to pump flow, mean arterial pressure, temperature, Hgb and PaCO₂. Deployment of the Cobra baffle reduced embolization to every brain region. Deployment of the baffle reduced total brain embolization by 89%. There was a mean of 61 ± 60 emboli per gram in the control animals and 7 ± 24 emboli per gram in those animals in which the baffle was deployed.

Conclusions. Cerebral embolization is profoundly reduced by use of the Cobra baffle aortic cannula. The application of this device may reduce postcardiac surgical neurologic injury.

	Introduction

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Embolization is an important cause of cardiac surgical neurologic morbidity. However, increased surgical attention to the atherosclerotic aorta, echocardiographic assessment of de-airing, and technical innovations, such as arterial line filters and membrane oxygenators, may improve patient outcomes. Clinical experience and a variety of reports indicate that quantitatively the greatest, and clinically most important, embolization during bypass originates in the heart and ascending aorta [1–3]. The aim of this study is to determine whether application of an endoaortic baffle to control flow distribution in the aortic arch could reduce brain embolization in a swine model of cardiopulmonary bypass. The device tested separates flow to the greater and lesser curvatures of the aortic arch by means of an inflatable baffle (Fig 1). Perfusion ports supplying the arch vessels are cephalad to the baffle and the port supplying the descending aorta is caudad to the baffle (Figs 1 and 2). Distribution of flow with this design protects the arch vessels from particulate entering the ascending aorta (Fig 3).

View larger version (17K): [in this window] [in a new window]   Fig 1. Schematic of Cobra catheter (Cardeon Corporation, Cupertino, CA).

View larger version (135K): [in this window] [in a new window]   Fig 2. Cutaway model of hemi-aortic arch with the Cobra catheter (Cardeon Corporation, Cupertino, CA) in place and baffle inflated. The catheter has perfusion ports, both cephalad and caudad or distal to the baffle. Arrows indicate the direction of flow from cannula perfusion ports.

View larger version (96K): [in this window] [in a new window]   Fig 3. Distribution of blue dye injected into the ascending aorta with 5 L per minute cannula water flow and the baffle inflated with green dye. The baffle prevents the blue dye from entering the arch vessels.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

Cardiopulmonary bypass was initiated and temperature was measured in the brain and inferior vena cava by needle and wire thermocouples, respectively. These were maintained at 36°C to 37°C, Hgb at 8 to 9.5 g · dL^-1, PaCO₂ at 35 to 40 mm Hg, and PaO₂ more than 150 mm Hg. Mean arterial blood pressure was maintained at 60 to 70 mm Hg by adjusting bypass pump flow rate. The target total bypass flow was 2.2 to 2.6 L · min/m². The arterial inflow line distal to the filter was split into ¹/₄- and ³/₈-inch lines. The ¹/₄-inch line was connected to the arch port of the cannula and the ³/₈-inch line to the descending aortic (corporeal) port of the cannula (Fig 1). Bypass flow in both lines was monitored by an ultrasonic flow probe. The proximal ascending aorta was cross-clamped.

After bypass was established the Cobra baffle (Cardeon Corporation, Cupertino, CA) was inflated in the eight treatment group animals. The baffle was inflated with saline, complete filling being indicated by inflation of a small external pilot balloon. In the control group the baffle remained undeployed. When steady state temperature, hemodynamic, and blood gas conditions were reached, an embolic load of 97 to 100 µm red fluorescent microspheres (excitation/emission wavelengths, 580/605 nm) (Molecular Probes, Eugene, OR) was given.

Seventy-two thousand microspheres were injected over 60 seconds into the proximal ascending aorta just distal to an aortic cross clamp. Microspheres were diluted in 9 mL of 6% dextran 70 with 0.025% tween 80, sonicated and vortexed, before injection [4, 5].

At completion of the experiment the heart was fibrillated and the brain removed. Tissue samples ( 1 g) of left and right temporal, frontal, and occipital lobes, and cerebellar hemispheres were obtained. In 6 of the animals (3 with the baffle deployed and 3 without), the eyes were removed and processed as a whole.

Blood and tissue samples were autolyzed in the dark for 2 weeks. Thereafter, microspheres were recovered from tissue by the sedimentation method [6, 7]. The intensity of fluorescence in tissue and blood samples was determined by a spectrofluorometer (SLM 8100, SLM-AMINCO, Rochester, NY). To determine the number of red fluorescent emboli per tissue sample, a standard curve with known concentrations of microspheres was constructed by analyzing serial dilutions of microspheres. The relationship between fluorescent intensity and microsphere number is essentially linear in dilute samples [8]. The fluorescence intensity (I_T) of the tissue sample was then determined and the concentration of microspheres was determined from a standard curve defined by the following equation:

where C = the number of microspheres, b = the Y intercept, and m = the slope of the the line.

Adequate mixing and equal distribution of microspheres was determined by comparing right-sided and left-sided tissue samples for each of four brain regions. If there was no statistical difference between sides (p > 0.05 by paired t test for each comparison), the two sides were averaged. Physiologic data and embolization between the two groups were compared using a t test. All data are presented as mean ± standard deviation. A p value less than 0.05 was considered significant.

	Results

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Systemic physiologic data at the time of embolization is presented in Table 1. None of the physiologic variables that might have affected embolization, mean arterial blood pressure, temperature, Hgb, or PaCO₂, differed between groups. In addition, neither group demonstrated a difference in mean arterial blood pressure between the arch and descending aortic circulations (Table 1). The total pump flow in the control group was 2.5 ± 0.5 L · min/m². Of that flow, 1.0 ± 0.3 L · min/m² was delivered through the aortic arch port of the cannula and 1.5 ± 0.3 L · min/m² through the descending aortic portion (Table 1). The mean total flow in the treatment animals was 2.6 ± 0.3 L · min/m². The mean flow to these circulations and the ratio of flow between the arch and descending aorta did not differ between the treatment and control groups (Table 1).

Embolization to each of the four brain regions is shown in Table 2. For every brain region the embolization was reduced when the endoaortic baffle was deployed. Relative to the control group, embolization to frontal, temporal, occipital lobes, and cerebellar hemispheres were reduced by a mean of 85%, 85%, 92%, and 89%, respectively. Across all brain regions sampled, the mean number of emboli per gram was 7 ± 24 in the treatment group and 61 ± 60 in the control group (Fig 4).

View larger version (8K): [in this window] [in a new window]   Fig 4. Embolization to the brain in animals undergoing embolization with the baffle deployed (left) and the baffle not deployed (right). Values are mean ± standard deviation. *p less than 0.05 by two sample T-test.

In the 6 animals in whom embolization to the eyes was determined, the mean number of emboli per gram was 7 ± 15 in the treatment group and 28 ± 10 in the control group.

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
The Cobra aortic catheter (Cardeon Corporation, Cupertino, CA) is a unique innovation. The cannula was the conceptual outgrowth of an earlier cannula designed to allow independent temperature control of the aortic arch and descending aorta [9]. The earlier device was also a dual-lumen cannula and separated perfusion of the aortic arch and descending aorta by means of an inflatable balloon positioned distal to the left subclavian artery. The device tested here also allows for independent control of arch and descending aortic temperatures; however, these circulations are separated not by a partially occluding balloon, but by an inflatable baffle positioned across the aortic arch segmenting flow along the lesser (descending aorta) and greater (arch vessels) curvatures (Fig 2). The Cobra device has perfusion ports supplying the arch vessels cephalad to the baffle, whereas the descending aorta is perfused through a port caudad and distal to the saline-inflated baffle.

In this experiment we chose to conduct these studies at normothermia, without independently controlling the arch and descending aortic temperatures. This allowed us to clearly determine the ability of the baffle to prevent cerebral embolization without having to delineate the separate effect of hypothermia. However, because hypothermia per se reduces cerebral embolization [5], we would have predicted an even greater reduction in cerebral embolization had we combined the effect of embolus deflection by the baffle with selective cooling of the aortic arch.

The Cobra device appears to prevent cerebral embolization in two ways. First, the position of the baffle in the transverse arch directs the blood in the ascending aorta (and emboli in that blood) preferentially along the lesser curvature of the arch (Fig 3). This distributes emboli originating in the proximal aorta to the lower two-thirds of the body. Cerebral embolization is also reduced by the relative distribution of flow between the arch and corporeal lumens of the device. The cannula is designed so the arch flow is high relative to the body surface area perfused, and higher per square meter of body surface area than that of the descending aortic flow. Because the cannula baffle is nonocclusive, this results in a shunting of excess blood from the greater curvature, proximally around the baffle and into the flow stream along the lesser curvature. This appears to effectively "wash" emboli away from the origin of the arch vessels.

A primary criticism of this study is that the Cobra device was not compared with a conventional aortic cannula. We chose to compare the device with and without the baffle deployed so we could clearly identify the effect of the baffle in reducing cerebral embolization. Had we chosen to compare this device against a standard aortic cannula, it would not be possible to determine if the reduction in embolization we demonstrate here was a function of the dual lumen nature of the Cobra device or the effect of the innovation of this device, the baffle. Additionally, a number of articles have already been published that provide a very good idea of the magnitude of cerebral embolization when a standard aortic cannula is used. In previous studies we have determined cerebral embolization using a standard aortic cannula (DLP 22 FR Ultraflex; Medtronic, Inc, Minneapolis, MN) in animals under several normothermic bypass conditions [4, 10]. Whereas the results are not directly comparable, the percentage of emboli delivered to the cortical brain regions during bypass with a standard aortic cannula was 3% to 6% of the total embolic load [4, 10]. Additionally, the fraction of emboli entering the cerebral circulation in humans has been estimated to be from 4% to 18% with standard aortic cannula [2]. Therefore, the results in the control group (no baffle deployment) are very similar to that seen with a standard aortic cannula.

Quantitatively, the effect of the Cobra device in reducing embolization is impressive. Earlier reports in the same model examined the effect of bypass temperature, flow, and PaCO₂ on brain embolization [4, 5, 10]. The effect of flow segmentation with the Cobra baffle reduced the percentage of emboli delivered to the brain by approximately 80% to 90%. This greatly exceeds what could be achieved with any of the previously described interventions.

A second criticism is that clinically, cerebral emboli consists of a variety of compositions and sizes that differ from uniform polystyrene emboli. Nevertheless, a 97 to 100 µm fluorescent microsphere is an excellent model. They approximate the size of emboli that occur during cardiopulmonary bypass [2, 11], and detection techniques allow us to detect as few as three emboli per gram of tissue. As such, the total embolization in this experiment approximates, or is less than, what may occur during clinical cardiopulmonary bypass. In addition, the results of this study should not differ if emboli of different composition or sizes are used. Because emboli of all sizes are carried in the stream of blood flow, the flow dynamics in the aortic arch generated with the Cobra device should affect a wide range of emboli types and sizes similarly. This discussion has bearing on another device currently being tested [12]. In contrast to the Cobra device described here, the efficacy of emboli filters or traps will be limited by sieving size. The majority of emboli generated during bypass are probably smaller than 120 µm [2, 11], so they would not be trapped by a filter of that mesh size.

One potential concern with directing emboli away from the origins of the arch vessels is the redistribution of that embolic material to other organ beds. While this will occur, it is important to appreciate that those emboli would be distributed to a much larger body mass, so the concentration effect should be quite small. In addition, the emboli directed down the descending aorta will be distributed to tissues with lower metabolic rates, greater vascular collateralization, and a much higher ischemic tolerance than the brain. Nevertheless, in subsequent studies, embolization to nonbrain regions must be determined.

Another primary concern with any endoaortic device, whether it is a cardiac catheterization, an intraaortic balloon pump, or an emboli trap, is the potential risk of embolization with device placement. While the subject of a pending report, the Cobra device has been used clinically in a recently completed feasibility trial. In those investigations, the ascending and descending aorta were graded for arteriosclerosis using transesophageal echocardiography, and device application was contingent on that assessment (with grade IV disease an exclusion criteria). Although severe atheromatous disease would be a relative contraindication to the use of any endoaortic device, severe disease is seen in a relatively small proportion of patients, (2% to 17% depending on technique and grading scale [13–15]). As such, this device or similar ones could have application in the majority of adults undergoing cardiac operations.

The primary finding of this study is that an endoaortic baffle can profoundly reduce cerebral embolization in a large animal model. Brain embolization is an important and potentially preventable cause of bypass-related neurologic injury, so application of this device may improve neurologic outcome. A clinical feasibility trial has been completed and a large multicenter, randomized, neurologic outcome trial with the Cobra device is being initiated.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Supported by a research grant from Cardeon Corp, Cupertino, CA.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

1. Clark R.E., Brillman J., Davis D.A., Lovell M.R., Price T.R., Magovern G.J. Microemboli during coronary artery bypass grafting. Genesis and effect on outcome. J Thorac Cardiovasc Surg 1995;109:249-258.[Abstract/Free Full Text]
2. Barbut D., Yao F.S.F., Lo Y.W., et al. Determination of size of aortic emboli and embolic load during coronary artery bypass grafting. Ann Thorac Surg 1997;63:1262-1267.[Abstract/Free Full Text]
3. van der Linden J., Casimir-Ahn H. When do cerebral emboli appear during open heart operations? A transcranial Doppler study. Ann Thorac Surg 1991;51:237-241.[Abstract]
4. Plochl W., Cook D.J. Quantification and distribution of cerebral emboli during cardiopulmonary bypass in the swine: the impact of PaCO₂. Anesthesiology 1999;90:183-190.[Medline]
5. Cook D.J., Plochl W., Orszulak T.A. Effect of temperature and PaCO₂ on cerebral embolization during cardiopulmonary bypass in swine. Ann Thorac Surg 2000;69:415-420.[Abstract/Free Full Text]
6. Van Oosterhout M.F., Prinzen F.W., Reneman R.S. The fluorescent microsphere method for determination of organ blood flow. FASEB J 1994;8:A854.
7. Van Oosterhout M.F., Willigers H.M., Reneman R.S., Prinzen F.W. Fluorescent microspheres to measure organ perfusion: validation of a simplified sample processing technique. Am J Physiol 1995;269:H725-H733.[Abstract/Free Full Text]
8. Glenny R.W., Bernard S., Brinkley M. Validation of fluorescent-labeled microspheres for measurement of regional organ perfusion. J Appl Physiol 1993;74:2585-2597.[Abstract/Free Full Text]
9. Boston U.S., Sungurtekin H., McGregor C., Macoviak J., Cook D.J. Differential perfusion: a new technique for isolated brain cooling during cardiopulmonary bypass. Ann Thorac Surg 2000;69:1346-1350.[Abstract/Free Full Text]
10. Sungurtekin H., Plochl W., Cook D.J. Relationship between cardiopulmonary bypass flow rate and cerebral embolization in dogs. Anesthesiology 1999;91:1387-1393.[Medline]
11. Moody D.M., Brown W.R., Challa V.R., Stump D.A., Reboussin D.M., Legault C. Brain microemboli associated with cardiopulmonary bypass: a histologic and magnetic resonance imaging study. Ann Thorac Surg 1995;59:1304-1307.[Abstract/Free Full Text]
12. Harringer W. Capture of particulate emboli during cardiac procedures in which aortic cross-clamp is used. International Council of Emboli Management Study Group. Ann Thorac Surg 2000;70:1119-1123.[Abstract/Free Full Text]
13. Mills N.L., Everson C.T. Atherosclerosis of the ascending aorta and coronary artery bypass. Pathology, clinical correlates, and operative management. J Thorac Cardiovasc Surg 1991;102:546-553.[Abstract]
14. Montgomery D.H., Ververis J.J., McGorisk G., Frohwein S., Martin R.P., Taylor W.R. Natural history of severe atheromatous disease of the thoracic aorta: a transesophageal echocardiographic study. J Am Coll Cardiol 1996;27:95-101.[Abstract]
15. Davila-Roman V.G., Phillips K.J., Daily B.B., Davila R.M., Kouchoukos N.T., Barzilai B. Intraoperative transesophageal echocardiography and epiaortic ultrasound for assessment of atherosclerosis of the thoracic aorta. J Am Coll Cardiol 1996;28:942-947.[Abstract]

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