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Published in: Journal of Cardiothoracic Surgery 1/2013

Open Access 01-12-2013 | Research article

Impact of bubble size in a rat model of cerebral air microembolization

Authors: Martin Juenemann, Mesut Yeniguen, Nadine Schleicher, Johannes Blumenstein, Max Nedelmann, Marlene Tschernatsch, Georg Bachmann, Manfred Kaps, Petr Urbanek, Markus Schoenburg, Tibo Gerriets

Published in: Journal of Cardiothoracic Surgery | Issue 1/2013

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Abstract

Background

Cerebral air microembolization (CAM) is a frequent side effect of diagnostic or therapeutic interventions. Besides reduction of the amount of bubbles, filter systems in the clinical setting may also lead to a dispersion of large gas bubbles and therefore to an increase of the gas–liquid-endothelium interface. We evaluated the production and application of different strictly defined bubble diameters in a rat model of CAM and assessed functional outcome and infarct volumes in relation to the bubble diameter.

Methods

Gas emboli of defined number and diameter were injected into the carotid artery of rats. Group I (n = 7) received 1800 air bubbles with a diameter of 45 μm, group II (n = 7) 40 bubbles of 160 μm, controls (n = 6) saline without gas bubbles; group I and II yielded the same total injection volume of air with 86 nl. Functional outcome was assessed at baseline, after 4 h and 24 h following cerebral MR imaging and infarct size calculation.

Results

Computer-aided evaluation of bubble diameters showed high constancy (group I: 45.83 μm ± 2.79; group II: 159 μm ± 1.26). Animals in group I and II suffered cerebral ischemia and clinical deterioration without significant difference. Infarct sizes did not differ significantly between the two groups (p = 0.931 u-test).

Conclusions

We present further development of a new method, which allows reliable and controlled CAM with different bubble diameters, producing neurological deficits due to unilateral cerebral damage. Our findings could not display a strong dependency of stroke frequency and severity on bubble diameter.
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Literature
1.
go back to reference Gupta R, Vora N, Thomas A, Crammond D, Roth R, Jovin T, Horowitz M: Symptomatic cerebral air embolism during neuro-angiographic procedures: incidence and problem avoidance. Neurocrit Care. 2007, 7: 241-246. 10.1007/s12028-007-0041-9.CrossRefPubMed Gupta R, Vora N, Thomas A, Crammond D, Roth R, Jovin T, Horowitz M: Symptomatic cerebral air embolism during neuro-angiographic procedures: incidence and problem avoidance. Neurocrit Care. 2007, 7: 241-246. 10.1007/s12028-007-0041-9.CrossRefPubMed
2.
go back to reference Gerriets T, Schwarz N, Sammer G, Baehr J, Stolz E, Kaps M, Kloevekorn W-P, Bachmann G, Schönburg M: Protecting the brain from gaseous and solid micro-emboli during coronary artery bypass grafting: a randomized controlled trial. Eur Heart J. 2010, 31: 360-368. 10.1093/eurheartj/ehp178.CrossRefPubMed Gerriets T, Schwarz N, Sammer G, Baehr J, Stolz E, Kaps M, Kloevekorn W-P, Bachmann G, Schönburg M: Protecting the brain from gaseous and solid micro-emboli during coronary artery bypass grafting: a randomized controlled trial. Eur Heart J. 2010, 31: 360-368. 10.1093/eurheartj/ehp178.CrossRefPubMed
3.
4.
go back to reference Bove AA, Hallenbeck JM, Elliott DH: Circulatory responses to venous air embolism and decompression sickness in dogs. Undersea Biomed Res. 1974, 1: 207-220.PubMed Bove AA, Hallenbeck JM, Elliott DH: Circulatory responses to venous air embolism and decompression sickness in dogs. Undersea Biomed Res. 1974, 1: 207-220.PubMed
5.
go back to reference Butler BD, Hills BA: Transpulmonary passage of venous air emboli. J Appl Physiol. 1985, 59: 543-547.PubMed Butler BD, Hills BA: Transpulmonary passage of venous air emboli. J Appl Physiol. 1985, 59: 543-547.PubMed
6.
go back to reference Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG, Blumenthal JA, Investigators NORGatCARE: Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Eng J Med. 2001, 344: 395-402. 10.1056/NEJM200102083440601.CrossRef Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG, Blumenthal JA, Investigators NORGatCARE: Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Eng J Med. 2001, 344: 395-402. 10.1056/NEJM200102083440601.CrossRef
7.
go back to reference Barak M, Katz Y: Microbubbles: pathophysiology and clinical implications. Chest. 2005, 128: 2918-2932. 10.1378/chest.128.4.2918.CrossRefPubMed Barak M, Katz Y: Microbubbles: pathophysiology and clinical implications. Chest. 2005, 128: 2918-2932. 10.1378/chest.128.4.2918.CrossRefPubMed
8.
go back to reference Malik AB, Johnson A, Tahamont MV: Mechanisms of lung vascular injury after intravascular coagulation. Ann N Y Acad Sci. 1982, 384: 213-234. 10.1111/j.1749-6632.1982.tb21374.x.CrossRefPubMed Malik AB, Johnson A, Tahamont MV: Mechanisms of lung vascular injury after intravascular coagulation. Ann N Y Acad Sci. 1982, 384: 213-234. 10.1111/j.1749-6632.1982.tb21374.x.CrossRefPubMed
9.
go back to reference Thorsen T, Dalen H, Bjerkvig R, Holmsen H: Transmission and scanning electron microscopy of N2 microbubble-activated human platelets in vitro. Undersea Biomed Res. 1987, 14: 45-58.PubMed Thorsen T, Dalen H, Bjerkvig R, Holmsen H: Transmission and scanning electron microscopy of N2 microbubble-activated human platelets in vitro. Undersea Biomed Res. 1987, 14: 45-58.PubMed
10.
go back to reference Warren BA, Philp RB, Inwood MJ: The ultrastructural morphology of air embolism: platelet adhesion to the interface and endothelial damage. Br J Exp Pathol. 1973, 54: 163-172.PubMedPubMedCentral Warren BA, Philp RB, Inwood MJ: The ultrastructural morphology of air embolism: platelet adhesion to the interface and endothelial damage. Br J Exp Pathol. 1973, 54: 163-172.PubMedPubMedCentral
11.
go back to reference Philp RB, Inwood MJ, Warren BA: Interactions between gas bubbles and components of the blood: implications in decompression sickness. Aerosp Med. 1972, 43: 946-953.PubMed Philp RB, Inwood MJ, Warren BA: Interactions between gas bubbles and components of the blood: implications in decompression sickness. Aerosp Med. 1972, 43: 946-953.PubMed
12.
go back to reference Lee WH, Hairston P: Structural effects on blood proteins at the gas-blood interface. Fed Proc. 1971, 30: 1615-1622.PubMed Lee WH, Hairston P: Structural effects on blood proteins at the gas-blood interface. Fed Proc. 1971, 30: 1615-1622.PubMed
13.
go back to reference Ward CA, Koheil A, McCullough D, Johnson WR, Fraser WD: Activation of complement at plasma-air or serum-air interface of rabbits. J Appl Physiol. 1986, 60: 1651-1658.PubMed Ward CA, Koheil A, McCullough D, Johnson WR, Fraser WD: Activation of complement at plasma-air or serum-air interface of rabbits. J Appl Physiol. 1986, 60: 1651-1658.PubMed
14.
go back to reference Weenink RP, Hollmann MW, Hulst RA: Animal models of cerebral arterial gas embolism. J Neurosci Methods. 2012, 205: 233-245. 10.1016/j.jneumeth.2011.12.025.CrossRefPubMed Weenink RP, Hollmann MW, Hulst RA: Animal models of cerebral arterial gas embolism. J Neurosci Methods. 2012, 205: 233-245. 10.1016/j.jneumeth.2011.12.025.CrossRefPubMed
15.
go back to reference Gerriets T, Walberer M, Nedelmann M, Doenges S, Ritschel N, Bachmann G, Stolz E, Kaps M, Urbanek S, Urbanek P, Schoenburg M: A rat model for cerebral air microembolisation. J Neurosci Methods. 2010, 190: 10-13. 10.1016/j.jneumeth.2010.04.016.CrossRefPubMed Gerriets T, Walberer M, Nedelmann M, Doenges S, Ritschel N, Bachmann G, Stolz E, Kaps M, Urbanek S, Urbanek P, Schoenburg M: A rat model for cerebral air microembolisation. J Neurosci Methods. 2010, 190: 10-13. 10.1016/j.jneumeth.2010.04.016.CrossRefPubMed
16.
go back to reference Nedelmann M, Wilhelm-Schwenkmezger T, Alessandri B, Heimann A, Schneider F, Eicke BM, Dieterich M, Kempski O: Cerebral embolic ischemia in rats: correlation of stroke severity and functional deficit as important outcome parameter. Brain Res. 2007, 1130: 188-196.CrossRefPubMed Nedelmann M, Wilhelm-Schwenkmezger T, Alessandri B, Heimann A, Schneider F, Eicke BM, Dieterich M, Kempski O: Cerebral embolic ischemia in rats: correlation of stroke severity and functional deficit as important outcome parameter. Brain Res. 2007, 1130: 188-196.CrossRefPubMed
17.
go back to reference Hamm RJ, Pike BR, O'Dell DM, Lyeth BG, Jenkins LW: The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. J Neurotrauma. 1994, 11: 187-196. 10.1089/neu.1994.11.187.CrossRefPubMed Hamm RJ, Pike BR, O'Dell DM, Lyeth BG, Jenkins LW: The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. J Neurotrauma. 1994, 11: 187-196. 10.1089/neu.1994.11.187.CrossRefPubMed
18.
go back to reference Gerriets T, Stolz E, Walberer M, Muller C, Rottger C, Kluge A, Kaps M, Fisher M, Bachmann G: Complications and pitfalls in rat stroke models for middle cerebral artery occlusion: a comparison between the suture and the macrosphere model using magnetic resonance angiography. Stroke. 2004, 35: 2372-2377. 10.1161/01.STR.0000142134.37512.a7.CrossRefPubMed Gerriets T, Stolz E, Walberer M, Muller C, Rottger C, Kluge A, Kaps M, Fisher M, Bachmann G: Complications and pitfalls in rat stroke models for middle cerebral artery occlusion: a comparison between the suture and the macrosphere model using magnetic resonance angiography. Stroke. 2004, 35: 2372-2377. 10.1161/01.STR.0000142134.37512.a7.CrossRefPubMed
19.
go back to reference Harringer W, Group obotICoEMS: Capture of particulate emboli during cardiac procedures in which aortic cross-clamp is used. Ann Thorac Surg. 2000, 70: 1119-1123. 10.1016/S0003-4975(00)01760-4.CrossRefPubMed Harringer W, Group obotICoEMS: Capture of particulate emboli during cardiac procedures in which aortic cross-clamp is used. Ann Thorac Surg. 2000, 70: 1119-1123. 10.1016/S0003-4975(00)01760-4.CrossRefPubMed
20.
go back to reference Banbury MK, Kouchoukos NT, Allen KB, Slaughter MS, Weissman NJ, Berry GJ, Horvath KA: Emboli capture using the Embol-X intraaortic filter in cardiac surgery: a multicentered randomized trial of 1,289 patients. Ann Thorac Surg. 2003, 76: 508-515. 10.1016/S0003-4975(03)00530-7.CrossRefPubMed Banbury MK, Kouchoukos NT, Allen KB, Slaughter MS, Weissman NJ, Berry GJ, Horvath KA: Emboli capture using the Embol-X intraaortic filter in cardiac surgery: a multicentered randomized trial of 1,289 patients. Ann Thorac Surg. 2003, 76: 508-515. 10.1016/S0003-4975(03)00530-7.CrossRefPubMed
21.
go back to reference Furlow TW: Experimental air embolism of the brain: an analysis of the technique in the rat. Stroke. 1982, 13: 847-852. 10.1161/01.STR.13.6.847.CrossRefPubMed Furlow TW: Experimental air embolism of the brain: an analysis of the technique in the rat. Stroke. 1982, 13: 847-852. 10.1161/01.STR.13.6.847.CrossRefPubMed
22.
go back to reference Helps SC, Parsons DW, Reilly PL, Gorman DF: The effect of gas emboli on rabbit cerebral blood flow. Stroke. 1990, 21: 94-99. 10.1161/01.STR.21.1.94.CrossRefPubMed Helps SC, Parsons DW, Reilly PL, Gorman DF: The effect of gas emboli on rabbit cerebral blood flow. Stroke. 1990, 21: 94-99. 10.1161/01.STR.21.1.94.CrossRefPubMed
23.
go back to reference van Hulst RA, Drenthen J, Haitsma JJ, Lameris TW, Visser GH, Klein J, Lachmann B: Effects of hyperbaric treatment in cerebral air embolism on intracranial pressure, brain oxygenation, and brain glucose metabolism in the pig*. Crit Care Med. 2005, 33: 841-846. 10.1097/01.CCM.0000159529.26114.CA.CrossRefPubMed van Hulst RA, Drenthen J, Haitsma JJ, Lameris TW, Visser GH, Klein J, Lachmann B: Effects of hyperbaric treatment in cerebral air embolism on intracranial pressure, brain oxygenation, and brain glucose metabolism in the pig*. Crit Care Med. 2005, 33: 841-846. 10.1097/01.CCM.0000159529.26114.CA.CrossRefPubMed
24.
go back to reference Jungwirth B, Kellermann K, Blobner M, Schmehl W, Kochs EF, Mackensen GB: Cerebral air emboli differentially alter outcome after cardiopulmonary bypass in rats compared with normal circulation. Anesthesiology. 2007, 107: 768-775. 10.1097/01.anes.0000287003.29685.c7.CrossRefPubMed Jungwirth B, Kellermann K, Blobner M, Schmehl W, Kochs EF, Mackensen GB: Cerebral air emboli differentially alter outcome after cardiopulmonary bypass in rats compared with normal circulation. Anesthesiology. 2007, 107: 768-775. 10.1097/01.anes.0000287003.29685.c7.CrossRefPubMed
25.
go back to reference Nozari A, Dilekoz E, Sukhotinsky I, Stein T, Eikermann-Haerter K, Liu C, Wang Y, Frosch MP, Waeber C, Ayata C, Moskowitz MA: Microemboli may link spreading depression, migraine aura, and patent foramen ovale. Ann Neurol. 2010, 67: 221-229. 10.1002/ana.21871.CrossRefPubMedPubMedCentral Nozari A, Dilekoz E, Sukhotinsky I, Stein T, Eikermann-Haerter K, Liu C, Wang Y, Frosch MP, Waeber C, Ayata C, Moskowitz MA: Microemboli may link spreading depression, migraine aura, and patent foramen ovale. Ann Neurol. 2010, 67: 221-229. 10.1002/ana.21871.CrossRefPubMedPubMedCentral
26.
go back to reference Qing M, Shim JK, Grocott HP, Sheng H, Mathew JP, Mackensen GB: The effect of blood pressure on cerebral outcome in a rat model of cerebral air embolism during cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2011, 142: 424-429. 10.1016/j.jtcvs.2010.11.036.CrossRefPubMed Qing M, Shim JK, Grocott HP, Sheng H, Mathew JP, Mackensen GB: The effect of blood pressure on cerebral outcome in a rat model of cerebral air embolism during cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2011, 142: 424-429. 10.1016/j.jtcvs.2010.11.036.CrossRefPubMed
27.
go back to reference Feinstein SB, Shah PM, Bing RJ, Meerbaum S, Corday E, Chang BL, Santillan G, Fujibayashi Y: Microbubble dynamics visualized in the intact capillary circulation. J Am Coll Cardiol. 1984, 4: 595-600. 10.1016/S0735-1097(84)80107-2.CrossRefPubMed Feinstein SB, Shah PM, Bing RJ, Meerbaum S, Corday E, Chang BL, Santillan G, Fujibayashi Y: Microbubble dynamics visualized in the intact capillary circulation. J Am Coll Cardiol. 1984, 4: 595-600. 10.1016/S0735-1097(84)80107-2.CrossRefPubMed
28.
go back to reference Hills BA, James PB: Microbubble damage to the blood–brain barrier: relevance to decompression sickness. Undersea Biomed Res. 1991, 18: 111-116.PubMed Hills BA, James PB: Microbubble damage to the blood–brain barrier: relevance to decompression sickness. Undersea Biomed Res. 1991, 18: 111-116.PubMed
29.
go back to reference Ritz-Timme S, Eckelt N, Schmidtke E, Thomsen H: Genesis and diagnostic value of leukocyte and platelet accumulations around “air bubbles” in blood after venous air embolism. Int J Legal Med. 1998, 111: 22-26.CrossRefPubMed Ritz-Timme S, Eckelt N, Schmidtke E, Thomsen H: Genesis and diagnostic value of leukocyte and platelet accumulations around “air bubbles” in blood after venous air embolism. Int J Legal Med. 1998, 111: 22-26.CrossRefPubMed
30.
go back to reference Bendszus M, Reents W, Franke D, Müllges W, Babin-Ebell J, Koltzenburg M, Warmuth-Metz M, Solymosi L: Brain Damage After Coronary Artery Bypass Grafting. Arch Neurol. 2002, 59: 1090-1095. 10.1001/archneur.59.7.1090.CrossRefPubMed Bendszus M, Reents W, Franke D, Müllges W, Babin-Ebell J, Koltzenburg M, Warmuth-Metz M, Solymosi L: Brain Damage After Coronary Artery Bypass Grafting. Arch Neurol. 2002, 59: 1090-1095. 10.1001/archneur.59.7.1090.CrossRefPubMed
31.
go back to reference Floyd TF, Shah PN, Price CC, Harris F, Ratcliffe SJ, Acker MA, Bavaria JE, Rahmouni H, Kuersten B, Wiegers S: Clinically silent cerebral ischemic events after cardiac surgery: their incidence, regional vascular occurrence, and procedural dependence. Ann Thorac Surg. 2006, 81: 2160-2166. 10.1016/j.athoracsur.2006.01.080.CrossRefPubMed Floyd TF, Shah PN, Price CC, Harris F, Ratcliffe SJ, Acker MA, Bavaria JE, Rahmouni H, Kuersten B, Wiegers S: Clinically silent cerebral ischemic events after cardiac surgery: their incidence, regional vascular occurrence, and procedural dependence. Ann Thorac Surg. 2006, 81: 2160-2166. 10.1016/j.athoracsur.2006.01.080.CrossRefPubMed
32.
go back to reference Knipp SC, Matatko N, Wilhelm H, Schlamann M, Massoudy P, Forsting M, Diener HC, Jakob H: Evaluation of brain injury after coronary artery bypass grafting. A prospective study using neuropsychological assessment and diffusion-weighted magnetic resonance imaging. Eur J Cardiothorac Surg. 2004, 25: 791-800. 10.1016/j.ejcts.2004.02.012.CrossRefPubMed Knipp SC, Matatko N, Wilhelm H, Schlamann M, Massoudy P, Forsting M, Diener HC, Jakob H: Evaluation of brain injury after coronary artery bypass grafting. A prospective study using neuropsychological assessment and diffusion-weighted magnetic resonance imaging. Eur J Cardiothorac Surg. 2004, 25: 791-800. 10.1016/j.ejcts.2004.02.012.CrossRefPubMed
33.
go back to reference Restrepo L, Wityk RJ, Grega MA, Borowicz L, Barker PB, Jacobs MA, Beauchamp NJ, Hillis AE, McKhann GM: Diffusion- and perfusion-weighted magnetic resonance imaging of the brain before and after coronary artery bypass grafting surgery. Stroke. 2002, 33: 2909-2915. 10.1161/01.STR.0000040408.75704.15.CrossRefPubMed Restrepo L, Wityk RJ, Grega MA, Borowicz L, Barker PB, Jacobs MA, Beauchamp NJ, Hillis AE, McKhann GM: Diffusion- and perfusion-weighted magnetic resonance imaging of the brain before and after coronary artery bypass grafting surgery. Stroke. 2002, 33: 2909-2915. 10.1161/01.STR.0000040408.75704.15.CrossRefPubMed
34.
go back to reference Schönburg M, Ziegelhoeffer T, Kraus B, Mühling A, Heidt M, Taborski U, Gerriets T, Roth M, Hein S, Urbanek S, Klövekorn WP: Reduction of gaseous microembolism during aortic valve replacement using a dynamic bubble trap. Gen Physiol Biophys. 2006, 25: 207-214.PubMed Schönburg M, Ziegelhoeffer T, Kraus B, Mühling A, Heidt M, Taborski U, Gerriets T, Roth M, Hein S, Urbanek S, Klövekorn WP: Reduction of gaseous microembolism during aortic valve replacement using a dynamic bubble trap. Gen Physiol Biophys. 2006, 25: 207-214.PubMed
35.
go back to reference Yoshitani K, de Lange F, Ma Q, Grocott HP, Mackensen GB: Reduction in air bubble size using perfluorocarbons during cardiopulmonary bypass in the rat. Anesth Analg. 2006, 103: 1089-1093. 10.1213/01.ane.0000244322.68977.18.CrossRefPubMed Yoshitani K, de Lange F, Ma Q, Grocott HP, Mackensen GB: Reduction in air bubble size using perfluorocarbons during cardiopulmonary bypass in the rat. Anesth Analg. 2006, 103: 1089-1093. 10.1213/01.ane.0000244322.68977.18.CrossRefPubMed
Metadata
Title
Impact of bubble size in a rat model of cerebral air microembolization
Authors
Martin Juenemann
Mesut Yeniguen
Nadine Schleicher
Johannes Blumenstein
Max Nedelmann
Marlene Tschernatsch
Georg Bachmann
Manfred Kaps
Petr Urbanek
Markus Schoenburg
Tibo Gerriets
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Cardiothoracic Surgery / Issue 1/2013
Electronic ISSN: 1749-8090
DOI
https://doi.org/10.1186/1749-8090-8-198

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