Abstract
The objective was to evaluate the feasibility and sensitivity of fluorescein to determine and delineate an ischemic area in an experimental model of acute coronary occlusion. The studies were performed at the center for experimental Surgery at Hospital de Clínicas “Jose de San Martin.” All animal protocols were approved by the Institutional Animal Care and Use Committee (IACUC) at University of Buenos Aires. All animals were maintained in a pathogen-free environment throughout the experiments. We used ten New Zeeland rabbits. They served as their own control model. All the experiments were performed under general anesthesia with tracheostomy. Median sternotomy was performed and the second diagonal artery was ligated. The infracted area was evaluated under xenon and UV (530 nm) light after the administration of 0.01 mg/kg fluorescein Fluorescein 10 % was intravenously administrated. Electrocardiogram (EKG), pulse oximetry, heart rate (HR), Troponin, CPK, CPK-MB, and LDH were determined postoperatively. All the animals were euthanized at the end of the experiment and the heart was harvested for histopathologic examination. Biochemical (enzymatic) and electrocardiography analyses were performed at baseline and at 90 min after complete occlusion of the second diagonal artery: Baseline (BL) and post-ischemic (PI) measurements were performed for LDH, CPK, CPK-MB, and Troponin. ST segment elevation of 1.8 ± 0.65 mm was detected in every case after coronary artery occlusion. Oxygen saturation and heart rate were 97 ± 2 % and 145 ± 5 % respectively. Enzymes results are: LDH (BL) 159.7 ± 112.2 (U/L) vs LDH (PI) 1,012 ± 359.9 (U/L) (p < 0.001). CPK (BL) 1,072 ± 121.7 (U/L) vs. CPK (PI) vs. 359.5 ± 95.7 (U/L) (p < 0.001), CPK-MB (BL) 0.89 ± 0.42 (ng/ml) vs CPK-MB (PI) vs. 3.89 ± 1.9 (ng/ml) (p < 0.001), Troponin (BL) 0.06 ± 0.06 (ng/ml) vs. Troponin (PI) 19.6 ± 5.9 (ng/ml) (p < 0.001). The xenon light failed to demonstrate any changes in the ischemic area. However, when evaluated under the UV (530 nm wave length) light, a clearly demarcated area lacking fluorescence can be appreciated. The area represented 0.7225 ± 0.39 cm2 in the anterior aspect of the myocardium distal to the ligated vessel. This was correlated and confirmed by microscopic evaluation. This study serves as a proof of principle that fluorescein detection of myocardial ischemia in an experimental model of acute coronary occlusion is feasible, sensitive, and reproducible. However, further clinical studies are required to understand if the findings of our study could be extrapolated into human studies.
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References
Valeur B. Molecular fluorescence: principles and applications, vol. 1. New York, NY: Wiley-VCH; 2001.
Podesser B, et al. Epicardial branches of the coronary arteries and their distribution in the rabbit heart: the rabbit heart as a model of regional ischemia. Anat Rec. 1997;247(4):521–7.
Kobayashi T, et al. Electrocardiograms corresponding to the development of myocardial infarction in anesthetized WHHLMI rabbits (Oryctolagus cuniculus), an animal model for familial hypercholesterolemia. Comp Med. 2012;62(5):409–18.
Jia C, Olafsson R, Kim K, Kolias TJ, Rubin JM, Weitzel WF, Witte RS, Huang SW, Richards MS, Deng CX, O’Donnell M. Two-dimensional strain imaging of controlled rabbit hearts. Ultrasound Med Biol. 2009;35(9):1488–501.
de Carvalho VB, Macruz R, Arie S, Martins JR, Pina RS, de Oliveira SA, Pileggi F, Décourt LV, Zerbini Ede J. Development of coronary atherosclerosis evaluated by cinecoronariography. Arq Bras Cardiol. 1980;34(6):431–9.
Soltesz EG, Laurence RG, De Grand AM, Cohn LH, Mihaljevic T, Frangioni JV. Image-guided quantification of cardioplegia delivery during cardiac surgery. Heart Surg Forum. 2007;10:E381–6.
Taggart DP, Choudhary B, Anastasiadis K, Abu-Omar Y, Balacumaraswami L, Pigott DW. Preliminary experience with a novel intraoperative fluorescence imaging technique to evaluate the patency of bypass grafts in total arterial revascularization. Ann Thorac Surg. 2003;75:870–3.
Nakayama A, et al. Functional near-infrared fluorescence imaging for cardiac surgery and targeted gene therapy. Mol Imaging. 2002;1(4):365–77.
Frangioni JV. In vivo near-infrared fluorescence imaging. Curr Opin Chem Biol. 2003;7:626–34.
De Grand AM, Frangioni JV. An operational near-infrared fluorescence imaging system prototype for large animal surgery. Technol Cancer Res Treat. 2003;2:553.
Eiichi TMD, Shunsuke Ohnishi MD, Rita G, Laurence B. Real-time intraoperative ureteral guidance using invisible near-infrared fluorescence. J Urol. 2007;178(5):2197–202.
Rangaraj AT, et al. Real-time visualization and quantification of retrograde cardioplegia delivery using near infrared fluorescent imaging. J Card Surg. 2008;23(6):701–8.
Nyarangi-Dix JN, Pahernik S, Bermejo JL, Prado L, Hohenfellner M. Significance of the intraoperative methylene blue test for postoperative evaluation of the vesicourethral anastomosis. Adv Urol. 2012;2012:702412.
van der Vorst JR, Schaafsma BE, Verbeek FP, Swijnenburg RJ, Hutteman M, Liefers GJ, van de Velde CJ, Frangioni JV, Vahrmeijer AL. Dose optimization for near-infrared fluorescence sentinel lymph node mapping in patients with melanoma. Br J Dermatol. 2013;168(1):93–8.
Ishizawa T, Fukushima N, Shibahara J, Masuda K, Tamura S, Aoki T, Hasegawa K, Beck Y, Fukayama M, Kokudo N. Real-time identification of liver cancers by using indocyanine green fluorescent imaging. Cancer. 2009;115(11):2491–504.
Diana M, Noll E, Diemunsch P, Dallemagne B, Benahmed MA, Agnus V, Soler L, Barry B, Namer IJ, Demartines N, Charles AL, Geny B, Marescaux J. Enhanced-reality video fluorescence. a real-time assessment of intestinal viability. Ann Surg. 2013;259:700.
Harrar N, Idali B, Moutaouakkil S, el Belhadji M, Zaghloul K, Amraoui A, Benaguida M. Anaphylactic shock caused by application of fluorescein on the ocular conjunctiva. Presse Med. 1996;25(32):1546–7. PMID 8952662 (in French).
Acknowledgements
The authors thank Giselle Romero, M.D. Staff Pathology Department, Hospital de Clínicas, “Jose de San Martin” University of Buenos Aires.
Lic.Paulo Daniel Pascuini. Economist, University of Buenos Aires.
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Dip, F.D. et al. (2015). Fluorescein Detection of Myocardial Ischemia in an Experimental Model of Acute Coronary Occlusion. In: Dip, F., Ishizawa, T., Kokudo, N., Rosenthal, R. (eds) Fluorescence Imaging for Surgeons. Springer, Cham. https://doi.org/10.1007/978-3-319-15678-1_33
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DOI: https://doi.org/10.1007/978-3-319-15678-1_33
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