Animal experimental study on the effects of different levels of amputation on cardiovascular system_Journal of Biomedical Engineering

Authors：

MIN Lei ^1,2 ,  JIANG Wentao ^1,2 , LI Zhongyou ^1,2 , LI Xiao ^1,2 , DIAO Junjie ^1,2 , LIU Renjing ^1,2 , TAI Tianxiang ^1,2 , BAI Taoping ^1,2

1. Department of Mechanics & Engineering, College of Architecture and Environment, Sichuan University, Chengdu 610065, P.R.China;
2. Sichuan Key Laboratory of Biomechanical Engineering, Sichuan University, Chengdu 610065, P.R.China;

Corresponding author：

JIANG Wentao, Email: scubme_jwt@outlook.com

Keywords：

Amputation levels; Cardiovascular system; Animal model; Biochemical index; Pathological examination

DOI：

10.7507/1001-5515.202211004

Video：

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Vascular injury resulting from lower limb amputation leads to the redistribution of blood flow and changes in vascular terminal resistance, which can affect the cardiovascular system. However, there was no clear understanding of how different amputation levels affect the cardiovascular system in animal experiments. Therefore, this study established two animal models of above-knee amputation (AKA) and below-knee amputation (BKA) to explore the effects of different amputation levels on the cardiovascular system through blood and histopathological examinations. The results showed that amputation caused pathological changes in the cardiovascular system of animals, including endothelial injury, inflammation, and angiosclerosis. The degree of cardiovascular injury was higher in the AKA group than in the BKA group. This study sheds light on the internal mechanisms of amputation’s impact on the cardiovascular system. Based on the amputation level of patients, the findings recommend more comprehensive and targeted monitoring after surgery and necessary interventions to prevent cardiovascular diseases.

Citation： MIN Lei, JIANG Wentao, LI Zhongyou, LI Xiao, DIAO Junjie, LIU Renjing, TAI Tianxiang, BAI Taoping. Animal experimental study on the effects of different levels of amputation on cardiovascular system. Journal of Biomedical Engineering, 2023, 40(3): 515-521. doi: 10.7507/1001-5515.202211004 Copy

1.	John T H, Bruce M K. 奈特人体生理学彩色图谱. 第1版. 北京: 人民卫生出版社, 2005: 66-78.
2.	Ochi M, Kohara K, Tabara Y, et al. Arterial stiffness is associated with low thigh muscle mass in middle-aged to elderly men. Atherosclerosis, 2010, 212(1): 327-332.
3.	Pyle A L, Young P P. Atheromas feel the pressure: biomechanical stress and atherosclerosis. Am J Pathol, 2010, 177(1): 4-9.
4.	Liao F, Garrison D W, Jan Y K. Relationship between nonlinear properties of sacral skin blood flow oscillations and vasodilatory function in people at risk for pressure ulcers. Microvasc Res, 2010, 80(1): 44-53.
5.	Nallegowda M, Lee E, Brandstater M, et al. Amputation and cardiac comorbidity: analysis of severity of cardiac risk. PM R, 2012, 4(9): 657-666.
6.	Stewart C P U, Jain A S. Cause of death of lower limb amputees. Prosthet Orthot Int, 1992, 16(2): 129.
7.	Yekutiel M, Brooks M E, Ohry A, et al. The prevalence of hypertension, ischaemic heart disease and diabetes in traumatic spinal cord injured patients and amputees. Spinal Cord, 1989, 27(1): 58-62.
8.	Naschitz J E. Why traumatic leg amputees are at increased risk for cardiovascular diseases. QJM-INT J Med, 2008, 101(4): 251-259.
9.	Jones W S, Patel M R, Dai D, et al. High mortality risks after major lower extremity amputation in Medicare patients with peripheral artery disease. Am Heart J, 2013, 165(5): 809-815.
10.	Aulivola B, Hile C N, Hamdan A D, et al. Major lower extremity amputation: outcome of a modern series. Arch Surg, 2004, 139(4): 395.
11.	Hrubec Z, Ryder R A. Traumatic limb amputations and subsequent mortality from cardiovascular disease and other causes. J Chronic Dis, 1980, 33(4): 239-250.
12.	Nerem R M. Hemodynamics and the vascular endotheliu. J Biomech Eng, 1993, 115(4B): 510-514.
13.	Ikeda M, Takei T, Mills I, et al. Calcium-independent activation of extracellular signal-regulated kinases 1 and 2 by cyclic strain. Biochem Bioph Res Co, 1998, 247(2): 462-465.
14.	Dua M M, Dalman R L. Hemodynamic influences on abdominal aortic aneurysm disease: application of biomechanics to aneurysm pathophysiology. Vascul Pharmacol, 2010, 53(1/2): 11-21.
15.	Vollmar J F, Pauschinger P, Paes E, et al. Aortic aneurysms as late sequelae of above-knee amputation. Lancet, 1989, 334(8667): 834-835.
16.	魏君如, 李忠友, 刁珺杰, 等. 下肢截肢水平对主动脉血流动力学影响的数值研究. 生物医学工程学杂志, 2022, 39(1): 67-74.
17.	Doyle B J, Callanan A, Burke P E, et al. Vessel asymmetry as an additional diagnostic tool in the assessment of abdominal aortic aneurysms. J Vasc Surg, 2009, 49(2): 443-454.
18.	Dong R, Jiang W, Zhang M, et al. Hemodynamic studies for lower limb amputation and rehabilitation. J Mech Med Biol, 2015, 15(4): 1530005.
19.	Samady H, Eshtehardi P, Mcdaniel M C, et al. Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease. Circulation, 2011, 124(7): 779-788.
20.	闵磊, 蒋文涛, 李忠友, 等. 研究截肢对心血管系统影响的动物模型建立. 生物医学工程学杂志, 2022, 39(5): 991-996.
21.	吴兆苏, 姚崇华, 赵冬, 等. 11省市队列人群心血管病发病前瞻性研究. 中华心血管病杂志, 1999(1): 5-8.
22.	Gordon T, Kannel W B, Castelli W P, et al. Lipoproteins, cardiovascular disease, and death: the Framingham Study. Arch Intern Med, 1981, 141(9): 1128-1131.
23.	Marques A, Marques M G, Silveira B C R, et al. Lidocaine administered at a continuous rate infusion does not impair left ventricular systolic and diastolic function of healthy rabbits sedated with midazolam. Vet Anim Sci, 2020, 10: 100151.
24.	Sun J H, Min D, Nam K, et al. Effect of dietary fats on blood cholesterol and lipid and the development of atherosclerosis in rabbits. Nutr Res, 2005, 25(10): 925-935.
25.	Anitschkow N. Uber die Veranderungen der Kannichenaorta bei experimentaeller Cholesterinsteatose. Beitrz Path Anatalllg Pathol, 1913, 56: 379-404.
26.	Troughton R W, Frampton C M, Yandle T G, et al. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet, 2000, 355(9210): 1126-1130.
27.	Rück A, Gustafsson T, Norrbom J, et al. ANP and BNP but not VEGF are regionally overexpressed in ischemic human myocardium. Biochem Bioph Res Co, 2004, 322(1): 287-291.
28.	江慧. 超声心动图联合BNP检测在慢性心力衰竭中的诊断价值分析. 基层医学论坛, 2021, 25(7): 978-979.
29.	Maisel A S, Krishnaswamy P, Nowak R M, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. New Engl J Med, 2002, 347(3): 161-167.
30.	Dahlström U. Can natriuretic peptides be used for the diagnosis of diastolic heart failure? Eur J Heart Fail, 2014, 6(3): 281-287.
31.	Ouma G O, Jonas R A, Usman M, et al. Targets and delivery methods for therapeutic angiogenesis in peripheral artery disease. Vasc Med, 2012, 17(3): 174-192.
32.	Jin H C, Eun H C. Angiogenesis in skin aging and photoaging. J Dermatol, 2010, 34(9): 593-600.
33.	Messina L M, Brevetti L S, Chang D S, et al. Therapeutic angiogenesis for critical limb ischemia: invited commentary. J Control Release, 2002, 78(1-3): 285-294.
34.	Wang Yongshun, Cao Wei, Cui Jinjin, et al. Arterial wall stress induces phenotypic switching of arterial smooth muscle cells in vascular remodeling by activating the YAP/TAZ signaling pathway. Cell Physiol Biochem, 2018, 51(2): 842-853.
35.	Yanni A E. The laboratory rabbit: an animal model of atherosclerosis research. Lab Anim, 2004, 38(3): 246-256.
36.	Weisbroth S H, Flatt R E, Kraus A L. The biology of the laboratory rabbit. New York: Academic Press, 2013: 155-156.
37.	Dutta S, Sengupta P. Rabbits and men: Relating their ages. J Basic Clin Physiol Pharmacol, 2018, 29(5): 427-435.
38.	Lafont A. Basic aspects of plaque vulnerability. Heart, 2003, 89(10): 1262-1267.
39.	Willerson J T, Ridker P M. Inflammation as a cardiovascular risk factor. Circulation, 2004, 109(21 Suppl 1): II-2-II-10.
40.	Franceschini G. Epidemiologic evidence for high-density lipoprotein cholesterol as a risk factor for coronary artery disease. Am J Cardiol, 2001, 88(12A): 9-13.
41.	诸骏仁, 高润霖, 赵水平, 等. 中国成人血脂异常防治指南(2016年修订版). 中国循环杂志, 2016, 31(10): 937-953.
42.	Magalhães P, Capingana D P, Silva A B T, et al. Arterial stiffness in lower limb amputees. Clin Med Insights Circ Respir Pulm Med, 2011, 5: 49-56.
43.	Keagy B A, Schwartz J A, Kotb M, et al. Lower extremity amputation: The control series. J Vasc Surg, 1986, 4(4): 321-326.
44.	Robinson K P. Long posterior flap amputation in geriatric patients with ischaemic disease. Ann Roy Coll Surg, 1976, 58(6): 440-451.
45.	Lim T S, Finlayson A, Thorpe J M, et al. Outcomes of a contemporary amputation series. ANZ J Surg, 2006, 76(5): 300-305.
46.	Resnick H E, Carter E A, Lindsay R, et al. Relation of lower-extremity amputation to all-cause and cardiovascular disease mortality in American Indians: The Strong Heart Study. Diabetes Care, 2004, 27(6): 1286-1293.
47.	Nehler M R, Coll J R, Hiatt W R, et al. Functional outcome in a contemporary series of major lower extremity amputations. J Vasc Surg, 2003, 38(1): 7-14.
48.	Low C K, Chew W Y C, Howe T S, et al. Factors affecting healing of below knee amputation. Singap Med J, 1996, 37(4): 392-393.
49.	Hunter G, Holliday P. Major amputation following vascular reconstructive procedures (including sympathectomy). Can J Surg, 1978, 21(5): 456-458.
50.	Yamaura H, Matsuzawa T. Decrease in capillary growth during aging. Can J Surg, 1980, 15(2): 145-150.
51.	Wietecha M S, Lin C, Ranzer M J, et al. Sprouty2 downregulates angiogenesis during mouse skin wound healing. Am J Physiol-Heart C, 2011, 300(2): H459-H467.

1. John T H, Bruce M K. 奈特人体生理学彩色图谱. 第1版. 北京: 人民卫生出版社, 2005: 66-78.
2. Ochi M, Kohara K, Tabara Y, et al. Arterial stiffness is associated with low thigh muscle mass in middle-aged to elderly men. Atherosclerosis, 2010, 212(1): 327-332.
3. Pyle A L, Young P P. Atheromas feel the pressure: biomechanical stress and atherosclerosis. Am J Pathol, 2010, 177(1): 4-9.
4. Liao F, Garrison D W, Jan Y K. Relationship between nonlinear properties of sacral skin blood flow oscillations and vasodilatory function in people at risk for pressure ulcers. Microvasc Res, 2010, 80(1): 44-53.
5. Nallegowda M, Lee E, Brandstater M, et al. Amputation and cardiac comorbidity: analysis of severity of cardiac risk. PM R, 2012, 4(9): 657-666.
6. Stewart C P U, Jain A S. Cause of death of lower limb amputees. Prosthet Orthot Int, 1992, 16(2): 129.
7. Yekutiel M, Brooks M E, Ohry A, et al. The prevalence of hypertension, ischaemic heart disease and diabetes in traumatic spinal cord injured patients and amputees. Spinal Cord, 1989, 27(1): 58-62.
8. Naschitz J E. Why traumatic leg amputees are at increased risk for cardiovascular diseases. QJM-INT J Med, 2008, 101(4): 251-259.
9. Jones W S, Patel M R, Dai D, et al. High mortality risks after major lower extremity amputation in Medicare patients with peripheral artery disease. Am Heart J, 2013, 165(5): 809-815.
10. Aulivola B, Hile C N, Hamdan A D, et al. Major lower extremity amputation: outcome of a modern series. Arch Surg, 2004, 139(4): 395.
11. Hrubec Z, Ryder R A. Traumatic limb amputations and subsequent mortality from cardiovascular disease and other causes. J Chronic Dis, 1980, 33(4): 239-250.
12. Nerem R M. Hemodynamics and the vascular endotheliu. J Biomech Eng, 1993, 115(4B): 510-514.
13. Ikeda M, Takei T, Mills I, et al. Calcium-independent activation of extracellular signal-regulated kinases 1 and 2 by cyclic strain. Biochem Bioph Res Co, 1998, 247(2): 462-465.
14. Dua M M, Dalman R L. Hemodynamic influences on abdominal aortic aneurysm disease: application of biomechanics to aneurysm pathophysiology. Vascul Pharmacol, 2010, 53(1/2): 11-21.
15. Vollmar J F, Pauschinger P, Paes E, et al. Aortic aneurysms as late sequelae of above-knee amputation. Lancet, 1989, 334(8667): 834-835.
16. 魏君如, 李忠友, 刁珺杰, 等. 下肢截肢水平对主动脉血流动力学影响的数值研究. 生物医学工程学杂志, 2022, 39(1): 67-74.
17. Doyle B J, Callanan A, Burke P E, et al. Vessel asymmetry as an additional diagnostic tool in the assessment of abdominal aortic aneurysms. J Vasc Surg, 2009, 49(2): 443-454.
18. Dong R, Jiang W, Zhang M, et al. Hemodynamic studies for lower limb amputation and rehabilitation. J Mech Med Biol, 2015, 15(4): 1530005.
19. Samady H, Eshtehardi P, Mcdaniel M C, et al. Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease. Circulation, 2011, 124(7): 779-788.
20. 闵磊, 蒋文涛, 李忠友, 等. 研究截肢对心血管系统影响的动物模型建立. 生物医学工程学杂志, 2022, 39(5): 991-996.
21. 吴兆苏, 姚崇华, 赵冬, 等. 11省市队列人群心血管病发病前瞻性研究. 中华心血管病杂志, 1999(1): 5-8.
22. Gordon T, Kannel W B, Castelli W P, et al. Lipoproteins, cardiovascular disease, and death: the Framingham Study. Arch Intern Med, 1981, 141(9): 1128-1131.
23. Marques A, Marques M G, Silveira B C R, et al. Lidocaine administered at a continuous rate infusion does not impair left ventricular systolic and diastolic function of healthy rabbits sedated with midazolam. Vet Anim Sci, 2020, 10: 100151.
24. Sun J H, Min D, Nam K, et al. Effect of dietary fats on blood cholesterol and lipid and the development of atherosclerosis in rabbits. Nutr Res, 2005, 25(10): 925-935.
25. Anitschkow N. Uber die Veranderungen der Kannichenaorta bei experimentaeller Cholesterinsteatose. Beitrz Path Anatalllg Pathol, 1913, 56: 379-404.
26. Troughton R W, Frampton C M, Yandle T G, et al. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet, 2000, 355(9210): 1126-1130.
27. Rück A, Gustafsson T, Norrbom J, et al. ANP and BNP but not VEGF are regionally overexpressed in ischemic human myocardium. Biochem Bioph Res Co, 2004, 322(1): 287-291.
28. 江慧. 超声心动图联合BNP检测在慢性心力衰竭中的诊断价值分析. 基层医学论坛, 2021, 25(7): 978-979.
29. Maisel A S, Krishnaswamy P, Nowak R M, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. New Engl J Med, 2002, 347(3): 161-167.
30. Dahlström U. Can natriuretic peptides be used for the diagnosis of diastolic heart failure? Eur J Heart Fail, 2014, 6(3): 281-287.
31. Ouma G O, Jonas R A, Usman M, et al. Targets and delivery methods for therapeutic angiogenesis in peripheral artery disease. Vasc Med, 2012, 17(3): 174-192.
32. Jin H C, Eun H C. Angiogenesis in skin aging and photoaging. J Dermatol, 2010, 34(9): 593-600.
33. Messina L M, Brevetti L S, Chang D S, et al. Therapeutic angiogenesis for critical limb ischemia: invited commentary. J Control Release, 2002, 78(1-3): 285-294.
34. Wang Yongshun, Cao Wei, Cui Jinjin, et al. Arterial wall stress induces phenotypic switching of arterial smooth muscle cells in vascular remodeling by activating the YAP/TAZ signaling pathway. Cell Physiol Biochem, 2018, 51(2): 842-853.
35. Yanni A E. The laboratory rabbit: an animal model of atherosclerosis research. Lab Anim, 2004, 38(3): 246-256.
36. Weisbroth S H, Flatt R E, Kraus A L. The biology of the laboratory rabbit. New York: Academic Press, 2013: 155-156.
37. Dutta S, Sengupta P. Rabbits and men: Relating their ages. J Basic Clin Physiol Pharmacol, 2018, 29(5): 427-435.
38. Lafont A. Basic aspects of plaque vulnerability. Heart, 2003, 89(10): 1262-1267.
39. Willerson J T, Ridker P M. Inflammation as a cardiovascular risk factor. Circulation, 2004, 109(21 Suppl 1): II-2-II-10.
40. Franceschini G. Epidemiologic evidence for high-density lipoprotein cholesterol as a risk factor for coronary artery disease. Am J Cardiol, 2001, 88(12A): 9-13.
41. 诸骏仁, 高润霖, 赵水平, 等. 中国成人血脂异常防治指南(2016年修订版). 中国循环杂志, 2016, 31(10): 937-953.
42. Magalhães P, Capingana D P, Silva A B T, et al. Arterial stiffness in lower limb amputees. Clin Med Insights Circ Respir Pulm Med, 2011, 5: 49-56.
43. Keagy B A, Schwartz J A, Kotb M, et al. Lower extremity amputation: The control series. J Vasc Surg, 1986, 4(4): 321-326.
44. Robinson K P. Long posterior flap amputation in geriatric patients with ischaemic disease. Ann Roy Coll Surg, 1976, 58(6): 440-451.
45. Lim T S, Finlayson A, Thorpe J M, et al. Outcomes of a contemporary amputation series. ANZ J Surg, 2006, 76(5): 300-305.
46. Resnick H E, Carter E A, Lindsay R, et al. Relation of lower-extremity amputation to all-cause and cardiovascular disease mortality in American Indians: The Strong Heart Study. Diabetes Care, 2004, 27(6): 1286-1293.
47. Nehler M R, Coll J R, Hiatt W R, et al. Functional outcome in a contemporary series of major lower extremity amputations. J Vasc Surg, 2003, 38(1): 7-14.
48. Low C K, Chew W Y C, Howe T S, et al. Factors affecting healing of below knee amputation. Singap Med J, 1996, 37(4): 392-393.
49. Hunter G, Holliday P. Major amputation following vascular reconstructive procedures (including sympathectomy). Can J Surg, 1978, 21(5): 456-458.
50. Yamaura H, Matsuzawa T. Decrease in capillary growth during aging. Can J Surg, 1980, 15(2): 145-150.
51. Wietecha M S, Lin C, Ranzer M J, et al. Sprouty2 downregulates angiogenesis during mouse skin wound healing. Am J Physiol-Heart C, 2011, 300(2): H459-H467.

Journal of Biomedical Engineering

Animal experimental study on the effects of different levels of amputation on cardiovascular system

Abstract Full text Figures/Tables Video References Cited by

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