臺灣博碩士論文加值系統

心臟生物指標（biomaker）主要可以分為兩大類，分別是結構性蛋白及功能性蛋白。其中最常被應用的結構性蛋白為心臟肌鈣蛋白I (cardiac troponin I)，負責測定各種造成心肌受損的疾病，是一種高敏感性及專一性的心臟生物指標。功能性蛋白N-terminal-pro B-type natriuretic peptide (NT-proBNP)是一種荷爾蒙，當細胞外液體過多造成心臟負擔時，心室壁會分泌此蛋白排出過多水分，維持體內正常循環。此論文包含兩個部份，第一部分研究心臟肌鈣蛋白I及NT-proBNP在健康及心臟瓣膜疾病之心衰竭患犬的血清濃度，第二部分研究治療前後心臟瓣膜疾病之心衰竭患犬心臟肌鈣蛋白I的濃度差異。研究結果指出心衰竭患犬血清的心臟肌鈣蛋白I及NT-proBNP濃度都明顯比健康犬高（分別為P=0.02, P<0.001），而且發現當心衰竭愈嚴重，血清中的心臟肌鈣蛋白I及NT-proBNP濃度愈高（分別為P=0.02, P<0.0001）。血清中心臟肌鈣蛋白I濃度，在治療後雖然明顯下降，但在統計結果並沒有顯著差異性存在（P=0.09）。根據此次的研究結果顯示測量血清中心臟肌鈣蛋白I及NT-proBNP濃度可以做為篩選是否罹患心臟疾病，並預測心衰竭嚴重程度。

Biomarkers have been extensively used in human and veterinary medicine, and divided into two groups: the leakage markers and functional makers. Cardiac troponin I (cTnI), a structure protein of cardiomyocyte, is a sensitive, specific, is a leakage marker for cardiac injury. N-terminal-pro B-type natriuretic peptide (NT-proBNP), a hormone exerts a variety of effects of maintaining circulatory homeostasis in states of increased extracellular volume, is a functional maker. The thesis includes two sections: first part, association NT-proBNP and cTnI of clinically healthy dogs and dogs with heart failure (HF); second part, changes of cTnI concentrations before and after treatment for HF. The result of this study illustrated that concentrations of NT-proBNP and cTnI in the dogs with HF were higher than those in the control dogs (P<0.001, P=0.02, respectively), and these two cardiac makers were positively associated with severity of HF (P<0.0001, P=0.02, respectively). Serum cTnI concentrations decreased after treatment, but not reach significant different (P=0.09). Based on these findings, both cardia markers were able to identify presence of cardiac disease, and determine severity of HF in dogs.

口試委員會審定書 i
Acknowledgment ii
Abstract iii
中文摘要 iv
Table of contents v
List of Tables vi
List of Figures vii
Chapter 1 General Introduction 1
Reference 4
Chapter 2 Serum concentration of NT-proBNP and cardiac troponin I in determination of severity of canine heart failure caused by chronic degenerative mitral valvular disease
8
Reference 15
Chapter 3 Changes of serum cardiac troponin I concentrations before and after treatment for congestive heart failure caused by chronic degenerative mitral valvular disease in dogs
22
Reference 28
Chapter 4 General discussion and conclusion 37

Chapter 1
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11.Dhoot GK, Perry SV. Distribution of polymorphic forms of troponin components and tropomyosin in skeletal muscle. Nature 1979;278:714-718.
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Chapter 2
1.Schober KE. Biochemical makers of cardiovascular disease. In: Ettinger SJ, Feldman EC. Textbook of veterinary internal medicine. 6th ed. Philadelphia: WB Saunders, 2005:940-947.
2.Sudoh T, Kangawa K, Minamino N, Matsuo H. A new natriuretic peptide in porcine brain. Nature 1988;332:78-81.
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4.Kazanegra R, Cheng V, Garcia A, et al. A rapid test for B-type natriuretic peptide correlates with falling wedge pressures in patients treated for decompensated heart failure: a pilot study. J Card Fail 2001;7:21-29.
5.Anand IS, Fisher LD, Chiang YT, et al. Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT). Circulation 2003;107:1278-1283.
6.Wijeysundera HC, Hansen MS, Stanton E, et al. Neurohormones and oxidative stress in nonischemic cardiomyopathy: relationship to survival and the effect of treatment with amlodipine. Am Heart J 2003;146:291-297.
7.Iwanaga Y, Nishi I, Furuichi S, et al. B-type natriuretic peptide strongly reflects diastolic wall stress in patients with chronic heart failure: comparison between systolic and diastolic heart failure. J Am Coll Cardiol 2006;47:742-748.
8.Boswood A, Dukes-McEwan J, Loureiro J, James RA, Martin M, Stafford-Johnson M, Smith P, Little C, Attree S. The diagnostic accuracy of different natriuretic peptides in the investigation of canine cardiac disease. J Small Anim Pract. 2008;49:26-32.
9.Oyama MA, Fox PR, Rush JE, Rozanski EA, Lesser M. Clinical utility of serum N-terminal pro-B-type natriuretic peptide concentration for identifying cardiac disease in dogs and assessing disease severity. J Am Vet Med Assoc. 2008 15;232:1496-503.
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11.Hori Y, Tsubaki M, Katou A, Ono Y, Yonezawa T, Li X, Higuchi SI. Evaluation of NT-pro BNP and CT-ANP as markers of concentric hypertrophy in dogs with a model of compensated aortic stenosis.J Vet Intern Med. 2008;22:1118-23.
12.Takeda S, Yamashita A, Maeda K, et al. Structure of the core domain of human cardiac troponin in the Ca (2+)-saturated form. Nature 2003;424:35-41.
13.Dhoot GK, Gell PG, Perry SV. The localization of the different forms of troponin I in skeletal and cardiac muscle cells. Exp Cell Res 1978;117:357-370.
14.Dhoot GK, Perry SV. Distribution of polymorphic forms of troponin components and tropomyosin in skeletal muscle. Nature 1979;278:714-718.
15.MacDonald KA, Kittleson MD, Munro C, Kass P. Brain natriuretic peptide concentration in dogs with heart disease and congestive heart failure. J Vet Intern Med 2003;17:172-177.
16.Maack T. The broad homeostatic role of natriuretic peptides. Arq Bras Endocrinol Metabol 2006;50:198-207.
17.Oyama MA, Sisson DD, Solter PF. Prospective screening for occult cardiomyopathy in dogs by measurement of plasma atrial natriuretic peptide, B-type natriuretic peptide, and cardiac troponin-I concentrations. Am J Vet Res 2007;68:42-47.
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23.Spratt DP, Mellanby RJ, Drury N, Archer J. Cardiac troponin I: evaluation I of a biomarker for the diagnosis of heart disease in the dog. J Small Anim Pract. 2005 ;46:139-45.

Chapter 3
1.Schober KE. Biochemical makers of cardiovascular disease. In: Ettinger SJ, Feldman EC. Textbook of veterinary internal medicine. 6th ed. Philadelphia: WB Saunders, 2005:940-947.
2.Ware WA. Management of heart failure. In: Nelson RW, Couto CG. Small animal internal medicine. 4th ed. St. Louis: Mosby Inc, 2009:53-62.
3.Takeda S, Yamashita A, Maeda K, Maeda Y. Structure of the core domain of human cardiac troponin in the Ca(2+)-saturated form. Nature 2003;424:35-41.
4.Dhoot GK, Gell PG, Perry SV. The localization of the different forms of troponin I in skeletal and cardiac muscle cells. Exp Cell Res 1978;117:357-370.
5.Dhoot GK, Perry SV. Distribution of polymorphic forms of troponin components and tropomyosin in skeletal muscle. Nature 1979;278:714-718.
6.Santalo Bel M, Guindo Soldevila J, Ordonez Llanos J. Biological markers of myocardial necrosis. Rev Esp Cardiol 2003;56:703-720.
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8.Packer M. Current role of beta-adrenergic blockers in the management of chronic heart failure. Am J Med. 2001;110:81S-94S
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