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DOI: 10.1055/s-0039-1687887
Experimental Studies for Small Diameter Grafts in an In Vivo Sheep Model—Techniques and Pitfalls
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Abstract
Background Scientific attempts to create the “ideal” small diameter vascular graft have been compared with the “search of the holy grail.” Prosthetic material as expanded polytetrafluoroethylene or Dacron shows acceptable patency rates to large caliber vessels, while small diameter (< 6 mm) prosthetic conduits present unacceptably poor patency rates. Vascular tissue engineering represents a promising option to address this problem.
Material and Methods Thirty-two female Texel-sheep aged 6 months to 2 years underwent surgical common carotid artery (CCA) interposition using different tissue-engineered vascular substitutes. Explantation of the grafts was performed 12 (n = 12) and 36 (n = 20) weeks after surgery. Ultrasound was performed on postoperative day 1 and thereafter every 4 weeks to evaluate the graft patency.
Results The average length of implanted substitutes was 10.3 ± 2.2 cm. Anesthesia and surgical procedure could be performed without major surgical complications in all cases.
The grafts showed a systolic blood flow velocity (BFV) of 28.24 ± 13.5 cm/s, a diastolic BFV of 9.25 ± 4.53 cm/s, and a mean BFV of 17.85 ± 9.25 cm/s. Native vessels did not differ relevantly in hemodynamic measurements (systolic: 29.77 cm/s; diastolic: 7.99 cm/s ± 5.35; mean 15.87 ± 10.75). There was no incidence of neurologic complications or subsequent postoperative occlusion. Perioperative morbidity was low and implantation of conduits was generally well tolerated.
Conclusion This article aims to give a precise overview of in vivo experiments in sheep for the evaluation of small diameter vascular grafts performing CCA interposition, especially with regard to pitfalls and possible perioperative complications and to discuss advantages and disadvantages of this approach.
Author contributions
Conception and design: KE, MG, TCWW, SM, JW.
Analysis and data interpretation: KE, MG, WB, MTW, SR, ID, AS, AM, ASK, TCWW, SM, JW.
Data collection: KE, MG, WB, MTW, SR, ID, AS, AM, ASK, TCWW, SM, JW.
Writing the article: KE, MG.
Critical revision of the article: KE, MG, WB, MTW, SR, ID, AS, AM, ASK, TCWW, SM, JW.
Final approval of the article: KE, MG, WB, MTW, SR, ID, AS, AM, ASK, TCWW, SM, JW.
SM and JW share the senior authorship.
∗ Both authors contributed equally to this manuscript.
Publikationsverlauf
Eingereicht: 25. Dezember 2018
Angenommen: 05. März 2019
Artikel online veröffentlicht:
28. April 2019
© 2019. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
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References
- 1 Diodato M, Chedrawy EG. Coronary artery bypass graft surgery: the past, present, and future of myocardial revascularisation. Surg Res Pract 2014; 2014: 726158
- 2 Beckmann A, Funkat AK, Lewandowski J. et al. Cardiac surgery in Germany during 2014: a report on behalf of the German Society for Thoracic and Cardiovascular Surgery. Thorac Cardiovasc Surg 2015; 63 (04) 258-269
- 3 The Vascular Surgical Society of Great Britain and Ireland. Critical limb ischaemia: management and outcome. Report of a national survey. Eur J Vasc Endovasc Surg 1995; 10 (01) 108-113
- 4 Raja SG, Haider Z, Ahmad M, Zaman H. Saphenous vein grafts: to use or not to use?. Heart Lung Circ 2004; 13 (02) 150-156
- 5 Veith FJ, Moss CM, Sprayregen S, Montefusco C. Preoperative saphenous venography in arterial reconstructive surgery of the lower extremity. Surgery 1979; 85 (03) 253-256
- 6 Seifalian AM, Tiwari A, Hamilton G, Salacinski HJ. Improving the clinical patency of prosthetic vascular and coronary bypass grafts: the role of seeding and tissue engineering. Artif Organs 2002; 26 (04) 307-320
- 7 Abbott WM, Green RM, Matsumoto T. et al; Above-Knee Femoropopliteal Study Group. Prosthetic above-knee femoropopliteal bypass grafting: results of a multicenter randomized prospective trial. J Vasc Surg 1997; 25 (01) 19-28
- 8 Conte MS. The ideal small arterial substitute: a search for the Holy Grail?. FASEB J 1998; 12 (01) 43-45
- 9 Kakisis JD, Liapis CD, Breuer C, Sumpio BE. Artificial blood vessel: the Holy Grail of peripheral vascular surgery. J Vasc Surg 2005; 41 (02) 349-354
- 10 Desai M, Seifalian AM, Hamilton G. Role of prosthetic conduits in coronary artery bypass grafting. Eur J Cardiothorac Surg 2011; 40 (02) 394-398
- 11 Byrom MJ, Bannon PG, White GH, Ng MK. Animal models for the assessment of novel vascular conduits. J Vasc Surg 2010; 52 (01) 176-195
- 12 Anderson DE, Glynn JJ, Song HK, Hinds MT. Engineering an endothelialized vascular graft: a rational approach to study design in a non-human primate model. PLoS One 2014; 9 (12) e115163
- 13 Fukayama T, Takagi K, Tanaka R. et al. Biological reaction to small-diameter vascular grafts made of silk fibroin implanted in the abdominal aortae of rats. Ann Vasc Surg 2015; 29 (02) 341-352
- 14 Toth C, Klarik Z, Kiss F, Toth E, Hargitai Z, Nemeth N. Early postoperative changes in hematological, erythrocyte aggregation and blood coagulation parameters after unilateral implantation of polytetrafluoroethylene vascular graft in the femoral artery of beagle dogs. Acta Cir Bras 2014; 29 (05) 320-327
- 15 Scherner M, Reutter S, Klemm D. et al. In vivo application of tissue-engineered blood vessels of bacterial cellulose as small arterial substitutes: proof of concept?. J Surg Res 2014; 189 (02) 340-347
- 16 Ueberrueck T, Tautenhahn J, Meyer L. et al. Comparison of the ovine and porcine animal models for biocompatibility testing of vascular prostheses. J Surg Res 2005; 124 (02) 305-311
- 17 Sardelic F, Fletcher JP, Ao PY, Bilous M. Comparison of fluoropolymer passivated Dacron and polytetrafluoroethylene grafts in a sheep model. Cardiovasc Surg 1994; 2 (02) 237-241
- 18 Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 2010; 8 (06) e1000412
- 19 Weber C, Reinhardt S, Eghbalzadeh K, Wacker M, Guschlbauer M, Maul A. et al. Patency and in vivo compatibility of bacterial nanocellulose grafts as small-diameter vascular substitute. J Vasc Surg 2018; 68 (6S): 177S-87S e1
- 20 American National Standard Association, for the Advancement of Medical Instrumentation Cardiovascular implants—tubular vascular prostheses. 2004;ANSI/AAMI/ISO 7198:1998/2001/(R) 2004
- 21 Baldwin BA. The anatomy of the arterial supply to the cranial regions of the sheep and ox. Am J Anat 1964; 115: 101-107
- 22 Baldwin BA, Bell FR. The anatomy of the cerebral circulation of the sheep and ox. The dynamic distribution of the blood supplied by the carotid and vertebral arteries to cranial regions. J Anat 1963; 97: 203-215
- 23 Baldwin BA, Bell FR. Blood flow in the carotid and vertebral arteries of the sheep and calf. J Physiol 1963; 167: 448-462
- 24 Baldwin BA, Bell FR. The effect on blood pressure in the sheep and calf of clamping some of the arteries contributing to the cephalic circulation. J Physiol 1963; 167: 463-479
- 25 Baldwin BA, Bell FR. The effect of temporary reduction in cephalic blood flow on the EEG of sheep and calf. Electroencephalogr Clin Neurophysiol 1963; 15: 465-475
- 26 Terlecki S, Baldwin BA, Bell FR. Experimental cerebral ischaemia in sheep. Neuropathology and clinical effects. Acta Neuropathol 1967; 7 (03) 185-200
- 27 James NL, Schindhelm K, Slowiaczek P. et al. In vivo patency of endothelial cell-lined expanded polytetrafluoroethylene prostheses in an ovine model. Artif Organs 1992; 16 (04) 346-353
- 28 May ND. Experimental studies of the collateral circulation in the head and neck of sheep (Ovis aries). J Anat 1968; 103 (Pt 1): 171-181
- 29 Jones DN, Rutherford RB, Ikezawa T, Nishikimi N, Ishibashi H, Whitehill TA. Factors affecting the patency of small-caliber prostheses: observations in a suitable canine model. J Vasc Surg 1991; 14 (04) 441-448 , discussion 448–451
- 30 Simoni G, Galleano R, Civalleri D. et al. Pharmacological control of intimal hyperplasia in small diameter polytetrafluoroethylene grafts. An experimental study. Int Angiol 1996; 15 (01) 50-56
- 31 Gross DR. Animal Models in Cardiovascular research. 2nd rev ed. London: Kluwer Academic; : Boston; 1994
- 32 Blunt MH. Cellular elements of ovine blood. In: Blunt MH. ed. The Blood of Sheep: Composition and Function. New York: Springer-Verlag; 1975: 29-44
- 33 Bull DA, Hunter GC, Holubec H, Aguirre ML, Rappaport WD, Putnam CW. Cellular origin and rate of endothelial cell coverage of PTFE grafts. J Surg Res 1995; 58 (01) 58-68
- 34 Swartz DD, Andreadis ST. Animal models for vascular tissue-engineering. Curr Opin Biotechnol 2013; 24 (05) 916-925
- 35 Tillman P, Carson SN, Talken L. Platelet function and coagulation parameters in sheep during experimental vascular surgery. Lab Anim Sci 1981; 31 (03) 263-267
- 36 Park SG, Kim SC, Choi MJ. et al. Heparin monitoring in sheep by activated partial thromboplastin time. Artif Organs 2003; 27 (06) 576-580
- 37 Connell JM, Khalapyan T, Al-Mondhiry HA, Wilson RP, Rosenberg G, Weiss WJ. Anticoagulation of juvenile sheep and goats with heparin, warfarin, and clopidogrel. ASAIO J 2007; 53 (02) 229-237
- 38 Spanos HG. Aspirin fails to inhibit platelet aggregation in sheep. Thromb Res 1993; 72 (03) 175-182
- 39 Urayama H, Kasashima F, Kawakami T, Kawakami K, Watanabe Y. An immunohistochemical analysis of implanted woven Dacron and expanded polytetrafluoroethylene grafts in humans. Artif Organs 1996; 20 (01) 24-29
- 40 Berger K, Sauvage LR, Rao AM, Wood SJ. Healing of arterial prostheses in man: its incompleteness. Ann Surg 1972; 175 (01) 118-127
- 41 Clowes AW, Kirkman TR, Clowes MM. Mechanisms of arterial graft failure. II. Chronic endothelial and smooth muscle cell proliferation in healing polytetrafluoroethylene prostheses. J Vasc Surg 1986; 3 (06) 877-884
- 42 Tillman BW, Yazdani SK, Lee SJ, Geary RL, Atala A, Yoo JJ. The in vivo stability of electrospun polycaprolactone-collagen scaffolds in vascular reconstruction. Biomaterials 2009; 30 (04) 583-588
- 43 Kaushal S, Amiel GE, Guleserian KJ. et al. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med 2001; 7 (09) 1035-1040
- 44 Dixit P, Hern-Anderson D, Ranieri J, Schmidt CE. Vascular graft endothelialization: comparative analysis of canine and human endothelial cell migration on natural biomaterials. J Biomed Mater Res 2001; 56 (04) 545-555
- 45 Abbott WM, Callow A, Moore W, Rutherford R, Veith F, Weinberg S. Evaluation and performance standards for arterial prostheses. J Vasc Surg 1993; 17 (04) 746-756
- 46 Narayanaswamy M, Wright KC, Kandarpa K. Animal models for atherosclerosis, restenosis, and endovascular graft research. J Vasc Interv Radiol 2000; 11 (01) 5-17
- 47 Rashid ST, Salacinski HJ, Hamilton G, Seifalian AM. The use of animal models in developing the discipline of cardiovascular tissue engineering: a review. Biomaterials 2004; 25 (09) 1627-1637
- 48 Trantina-Yates A, Weissenstein C, Human P, Zilla P. Stentless bioprosthetic heart valve research: sheep versus primate model. Ann Thorac Surg 2001; 71 (5, Suppl): S422-S427
- 49 Goodman SL. Sheep, pig, and human platelet-material interactions with model cardiovascular biomaterials. J Biomed Mater Res 1999; 45 (03) 240-250