Cachexia and Sarcopenia in Companion Animals: An Under-Utilized Natural Animal Model of Human Disease

Lisa M. Freeman

Abstract


While laboratory small animal models of cachexia and sarcopenia are well-suited and critical for studying mechanisms and early pre-clinical phases for potential treatments, they are not similar enough to the human conditions to always be good predictors for results in human clinical trials.  As a result, translational failures can occur when large-scale human clinical trials are conducted on drugs, even when they appear promising in pre-clinical studies in rodent models.  What is needed is a way to more efficiently and successfully translate information gained from basic science and rodent research into human clinical trials that produce effective approved drugs.  Naturally-occurring cachexia and sarcopenia in companion animals is a more representative model of human disease that can serve as a stepping stone between basic science and human clinical trials.  Many of the common diseases of humans also affect companion animals, particularly pet dogs and cats.  Pet dogs and cats commonly develop heart failure, cancer, and kidney disease, as well as acute trauma or illness.  The population of elderly companion animals also is increasing as pets’ lifespans have become longer.  As a result, both cachexia and sarcopenia are very common in companion animals.  Studying these conditions in dogs and cats – either in colonies or in animal clinical trials - can help to identify successful treatments that can benefit both humans and companion animals.   


Full Text:

PDF

References


von Haehling S, Anker MS, Anker SD. Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and Japan: facts and numbers update 2016. J Cachexia Sarcopenia Muscle. 2016;7(5):507-9.

Konishi M, Ebner N, von Haehling S, Anker SD, Springer J. Developing models for cachexia and their implications in drug discovery. Exp Opin Drug Discov. 2015;10(7):743-52.

Molinari F, Malara N, Mollace V, Rosano G, Ferraro E. Animal models of cardiac cachexia. Int J Cardiol. 2016;219:105-10.

Mueller TC, Bachmann J, Prokopchuk O, Friess H, Martignoni ME. Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia - can findings from animal models be translated to humans? BMC Cancer. 2016 Feb 8;16:75. doi: 10.1186/s12885-016-2121-8.

Penna F, Busquets S, Argiles JM. Experimental cancer cachexia: Evolving strategies for getting closer to the human scenario. Sem Cell Develop Biol. 2016;54:20-7..

Ballaro R, Costelli P, Penna F. Animal models for cancer cachexia. Curr opin support palliat care. 2016;10(4):281-7.

Ishida J, Saitoh M, Doehner W, von Haehling S, Anker M, Anker SD et al. Animal models of cachexia and sarcopenia in chronic illness: Cardiac function, body composition changes and therapeutic results. Int J Cardiol. 2017;238:12-8.

Thomas D, Burns J, Audette J, Carroll A, Dow-Hygelund C, Hay M. Clinical development success rates 2006-2015. BIO, Biomedtracker, Amplion, 2016.

Freeman LM. Cachexia and sarcopenia: emerging syndromes of importance in dogs and cats. J Vet Intern Med. 2012;26(1):3-17.

Brooks D, Churchill J, Fein K, Linder D, Michel KE, Tudor K et al. 2014 AAHA weight management guidelines for dogs and cats. J Am Anim Hosp Assoc. 2014;50(1):1-11.

Lyons LA, Biller DS, Erdman CA, Lipinski MJ, Young AE, Roe BA et al. Feline polycystic kidney disease mutation identified in PKD1. J Am Soc Nephrol. 2004;15(10):2548-55.

American Pet Products Association. 2017-2018 National Pet Owners Survey. http://www.americanpetproducts.org/press_industrytrends.asp. Accessed 31 August, 2017.

Doria-Rose VP, Scarlett JM. Mortality rates and causes of death among emaciated cats. J Am Vet Med Assoc. 2000;216(3):347-51.

Mallery KF, Freeman LM, Harpster NK, Rush JE. Factors contributing to the decision for euthanasia of dogs with congestive heart failure. J Am Vet Med Assoc. 1999;214(8):1201-4.

Lang T, Streeper T, Cawthon P, Baldwin K, Taaffe DR, Harris TB. Sarcopenia: etiology, clinical consequences, intervention, and assessment. Osteoporosis intl. 2010;21(4):543-59.

Lawler DF, Evans RH, Larson BT, Spitznagel EL, Ellersieck MR, Kealy RD. Influence of lifetime food restriction on causes, time, and predictors of death in dogs. J Am Vet Med Assoc. 2005;226(2):225-31.

Hua J, Hoummady S, Muller C, Pouchelon JL, Blondot M, Gilbert C et al. Assessment of frailty in aged dogs. Am J Vet Res. 2016;77(12):1357-65.

Evans WJ, Morley JE, Argiles J, Bales C, Baracos V, Guttridge D et al. Cachexia: a new definition. Clin Nutr. 2008;27:6.

Morley JE, Abbatecola AM, Argiles JM, Baracos V, Bauer J, Bhasin S et al. Sarcopenia with limited mobility: an international consensus. J Am Med Dir Assoc. 2011;12(6):403-9.

Swimmer RA, Rozanski EA. Evaluation of the 6-minute walk test in pet dogs. J Vet Intern Med. 2011;25(2):405-6.

Acosta AR, Van Wie E, Stoughton WB, Bettis AK, Barnett HH, LaBrie NR et al. Use of the six-minute walk test to characterize golden retriever muscular dystrophy. Neuromusc disorders. 2016;26(12):865-72.

Hutchinson D, Sutherland-Smith J, Watson AL, Freeman LM. Assessment of methods of evaluating sarcopenia in old dogs. Am J Vet Res. 2012;73(11):1794-800.

Laflamme D. Development and validation of a body condition score system for dogs. Canine Pract. 1997;22.

Laflamme DP. Development and validation of a body condition score system for cats. Feline Pract. 1997;25:13-8.

Michel KE, Anderson W, Cupp C, Laflamme DP. Correlation of a feline muscle mass score with body composition determined by dual-energy X-ray absorptiometry. Br J Nutr. 2011;106 Suppl 1:S57-9.

World Small Animal Veterinary Association Global Nutrition Committee. Muscle condition score chart. http://www.wsava.org/nutrition-toolkit. Accessed 31 August, 2017.

Baldwin K, Bartges J, Buffington T, Freeman LM, Grabow M, Legred J et al. AAHA nutritional assessment guidelines for dogs and cats. J Am Anim Hosp Assoc. 2010;46(4):285-96.

Freeman L, Becvarova I, Cave N, MacKay C, Nguyen P, Rama B et al. WSAVA Nutritional Assessment Guidelines. J Small Anim Pract. 2011;52(7):385-96.

Freeman LM, Sutherland-Smith J, L.R. P, Rush JE, Barton BA. Quantitative assessment of muscle in dogs using a vertebral epaxial muscle score. Can J Vet Res. In Press.

Whitney JC. Observations on the effect of age on the severity of heart valve lesions in the dog. J Small Anim Pract. 1974;15(8):511-22.

Buchanan JW. Prevalence of cardiovascular disorders. 2nd ed ed. Textbook of canine and feline cardiology. Philadelphia: WB Saunders; 1999, pp 457-70.

Meurs KM. Arrhythmogenic right ventricular cardiomyopathy in the boxer dog. Vet Clin N Am: Small Anim Pract. 2017;47(5):1103-11.

Wess G, Schulze A, Butz V, Simak J, Killich M, Keller LJ et al. Prevalence of dilated cardiomyopathy in Doberman Pinschers in various age groups. J Vet Intern Med. 2010;24(3):533-8.

Beardow AW, Buchanan JW. Chronic mitral valve disease in cavalier King Charles spaniels: 95 cases (1987-1991). J Am Vet Med Assoc. 1993;203(7):1023-9.

Payne JR, Brodbelt DC, Luis Fuentes V. Cardiomyopathy prevalence in 780 apparently healthy cats in rehoming centres (the CatScan study). J Vet Cardiol. 2015;17, Supplement 1:S244-S57.

Freeman LM, Rush JE, Stern JA, Huggins GS, Maron MS. Feline hypertrophic cardiomyopathy: a spontaneous large animal model of human HCM. Cardiol Res. 2017;8. doi:https://doi.org/10.14740/cr578w.

Kittleson MD, Meurs KM, Harris SP. The genetic basis of hypertrophic cardiomyopathy in cats and humans. J Vet Cardiol. 2015;17 Suppl 1:S53-73.

Freeman LM, Rush JE, Kehayias JJ, Ross JN, Meydani SN, Brown DJ et al. Nutritional alterations and the effect of fish oil supplementation in dogs with heart failure. J Vet Intern Med. 1998;12:440-8.

Slupe JL, Freeman LM, Rush JE. Association of body weight and body condition with survival in dogs with heart failure. J Vet Intern Med. 2008;22(3):561-5.

Finn E, Freeman LM, Rush JE, Lee Y. The relationship between body weight, body condition, and survival in cats with heart failure. J Vet Intern Med. 2010;24(6):1369-74.

Freeman LM, Rush JE. Relationship between cachexia and lymphocyte subpopulations and hematologic parameters in dogs with spontaneously-occurring congestive heart failure. Proceedings of the 3rd Cachexia Conference, Rome, Italy, December, 2005. 2005:83.

Sharma A, Lavie CJ, Borer JS, Vallakati A, Goel S, Lopez-Jimenez F et al. Meta-analysis of the relation of body mass index to all-cause and cardiovascular mortality and hospitalization in patients with chronic heart failure. Am J Cardiol. 2015;115(10):1428-34.

Lavie CJ, De Schutter A, Patel DA, Romero-Corral A, Artham SM, Milani RV. Body composition and survival in stable coronary heart disease: impact of lean mass index and body fat in the "obesity paradox". J Am Coll Cardiol. 2012;60(15):1374-80.

Meurs KM, Fox PR, Miller MW, Kapadia S, Mann DL. Plasma concentrations of tumor necrosis factor-alpha in cats with congestive heart failure. Am J Vet Res. 2002;63:640-2.

Fonfara S, Hetzel U, Tew SR, Dukes-McEwan J, Cripps P, Clegg PD. Leptin expression in dogs with cardiac disease and congestive heart failure. J Vet Intern Med. 2011;25(5):1017-24.

Kim HS, Kang JH, Jeung EB, Yang MP. Serum concentrations of leptin and adiponectin in dogs with myxomatous mitral valve disease. J Vet Intern Med. 2016;30(5):1589-1600.

Petretta M, Colao A, Sardu C, Scopacasa F, Marzullo P, Pivonello R et al. NT-proBNP, IGF-I and survival in patients with chronic heart failure. Growth Horm IGF Res. 2007;17(4):288-96.

Freeman LM, Rush JE, Cahalane AK, Kaplan PM, Markwell PJ. Evaluation of dietary patterns in dogs with cardiac disease. J Am Vet Med Assoc 2003;223(9):1301-5.

Torin DS, Freeman LM, Rush JE. Dietary patterns of cats with cardiac disease. J Am Vet Med Assoc. 2007;230(6):862-7.

National Cancer Institute Center for Cancer Research Comparative Oncology Program. National Cancer Institute Center for Cancer Research Comparative Oncology Program. https://ccrod.cancer.gov/confluence/display/CCRCOPWeb/Home+BA

CKUP. Accessed 31 August, 2017.

Guy MK, Page RL, Jensen WA, Olson PN, Haworth JD, Searfoss EE et al. The Golden Retriever Lifetime Study: establishing an observational cohort study with translational relevance for human health. Phil trans Royal Soc London Ser B. 2015;370(1673). doi:10.1098/rstb.2014.0230.

Proschowsky HF, Rugbjerg H, Ersboll AK. Mortality of purebred and mixed-breed dogs in Denmark. Prevent Vet Med. 2003;58(1-2):63-74.

Adams VJ, Evans KM, Sampson J, Wood JL. Methods and mortality results of a health survey of purebred dogs in the UK. J Small Anim Pract. 2010;51(10):512-24.

Fleming JM, Creevy KE, Promislow DEL. Mortality in North American dogs from 1984 to 2004: an investigation into age-, size-, and breed-related causes of death. J Vet Intern Med. 2011;25(2):187-98.

Reif J. The epidemiology and incidence of cancer. In: Withrow S, Vail D, editors. Small animal clinical oncology. 4th ed ed. St Louis: Saunders Elsevier; 2007. pp. 68-76.

Dobson JM. Breed-predispositions to cancer in pedigree dogs. ISRN Vet Sci. 2013;2013:941275.

Gardner HL, Fenger JM, London CA. Dogs as a model for cancer. Ann Rev Anim Biosciences. 2016;4:199-222.

Ito D, Frantz AM, Modiano JF. Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications. Vet Immunol Immunopathol. 2014;159(3-4):192-201.

Canine Comparative Oncology and Genomics Consortium. http://ccogc.net/. Accessed 31 August, 2017.

Michel KE, Sorenmo K, Shofer FS. Evaluation of body condition and weight loss in dogs presented to a veterinary oncology service. J Vet Intern Med. 2004;18(5):692-5.

Weeth LP, Fascetti AJ, Kass PH, Suter SE, Santos AM, Delaney SJ. Prevalence of obese dogs in a population of dogs with cancer. Am J Vet Res. 2007;68(4):389-98.

Romano FR, Heinze CR, Barber LG, Mason JB, Freeman LM. Association between body condition score and cancer prognosis in dogs with lymphoma and osteosarcoma. J Vet Intern Med. 2016:30(4):1179-86.

Baez JL, Michel KE, Sorenmo K, Shofer FS. A prospective investigation of the prevalence and prognostic significance of weight loss and changes in body condition in feline cancer patients. J Fel Med Surg. 2007;9(5):411-7.

Polzin DJ. Chronic kidney disease. In: Ettinger SJ, Feldman EC, Cote E, editors. Textbook of veterinary internal medicine. St Louis: Elsevier; 2017. pp. 1938-59.

Marino CL, Lascelles BD, Vaden SL, Gruen ME, Marks SL. Prevalence and classification of chronic kidney disease in cats randomly selected from four age groups and in cats recruited for degenerative joint disease studies. J Feline Med Surg. 2014;16(6):465-72.

O'Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC. Longevity and mortality of cats attending primary care veterinary practices in England. J Feline Med Surg. 2015;17(2):125-33.

DiBartola SP, Rutgers HC, Zack PM, Tarr MJ. Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973-1984). J Am Vet Med Assoc. 1987;190(9):1196-202.

Elliott J, Barber PJ. Feline chronic renal failure: clinical findings in 80 cases diagnosed between 1992 and 1995. J Small Anim Pract. 1998;39(2):78-85.

Goldstein RE, Marks SL, Cowgill LD, Kass PH, Rogers QR. Plasma amino acid profiles in cats with naturally acquired chronic renal failure. Am J Vet Res. 1999;60(1):109-13.

Boyd LM, Langston C, Thompson K, Zivin K, Imanishi M. Survival in cats with naturally occurring chronic kidney disease (2000-2002). J Vet Intern Med. 2008;22(5):1111-7.

Greene JP, Lefebvre SL, Wang M, Yang M, Lund EM, Polzin DJ. Risk factors associated with the development of chronic kidney disease in cats evaluated at primary care veterinary hospitals. J Am Vet Med Assoc. 2014;244(3):320-7.

Freeman LM, Lachaud MP, Matthews S, Rhodes L, Zollers B. Evaluation of weight loss over time in cats with chronic kidney disease. J Vet Intern Med. 2016;30(5):1661-6.

King JN, Tasker S, Gunn-Moore DA, Strehlau G. Prognostic factors in cats with chronic kidney disease. J Vet Intern Med. 2007;21(5):906-16.

Ahmadi SF, Zahmatkesh G, Ahmadi E, Streja E, Rhee CM, Gillen DL et al. Association of body mass index with clinical outcomes in non-dialysis-dependent chronic kidney disease: a systematic review and meta-analysis. Cardiorenal Med. 2015;6(1):37-49.

Ahmadi SF, Zahmatkesh G, Streja E, Mehrotra R, Rhee CM, Kovesdy CP et al. Association of body mass index with mortality in peritoneal dialysis patients: a systematic review and meta-analysis. Peritoneal Dialysis Intl. 2016;36(3):315-25.

Parker VJ, Freeman LM. Association between body condition and survival in dogs with acquired chronic kidney disease. J Vet Intern Med. 2011;25(6):1306-11.

Markovich JE, Freeman LM, Labato MA, Heinze CR. Survey of dietary and medication practices of owners of cats with chronic kidney disease. J Fel Med Surg. 2015;17(12):979-83.

Meyer J, Stadtfeld G. Investigation on the body and organ structure of dogs. In: Anderson RS, editor. Nutrition of the Dog and Cat. Oxford, UK: Pergamon Press; 1980. pp. 15-30.

Munday HS, Earle KE, Anderson P. Changes in the body composition of the domestic shorthaired cat during growth and development. J Nutr. 1994;124:2622S-3S.

Harper E. Changing perspectives on aging and energy requirements: Aging, body weight and body composition in humans, dogs and cats. J Nutr. 1998;128:2627S-31S.

Lawler DF, Larson BT, Ballam JM, Smith GK, Biery DN, Evans RH et al. Diet restriction and ageing in the dog: major observations over two decades. Br J Nutr. 2009;99(4):793-805.

Fearon K, Arends J, Baracos V. Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev. Clin Oncol. 2013;10(2):90-9.

Cohen S, Nathan JA, Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov. 2015;14(1):58-74.

von Haehling S. Wasting away: How to treat cachexia and muscle wasting in chronic disease? Br J Clin Pharm. 2017. doi:10.1111/bcp.13387.

von Haehling S, Ebner N, dos Santos MR, Springer J, Anker SD. Muscle wasting and cachexia in heart failure: mechanisms and therapies. Nat Rev Cardiol. 2017;14(6):323-41.

McPherron AC, Lee SJ. Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci USA. 1997;94(23):12457-61.

Kambadur R, Sharma M, Smith TP, Bass JJ. Mutations in myostatin (GDF8) in double-muscled Belgian Blue and Piedmontese cattle. Genome Res. 1997;7(9):910-6.

Grobet L, Martin LJ, Poncelet D, Pirottin D, Brouwers B, Riquet J et al. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genetics. 1997;17(1):71-4.

Clop A, Marcq F, Takeda H, Pirottin D, Tordoir X, Bibe B et al. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat Genetics. 2006;38(7):813-8.

Schuelke M, Wagner KR, Stolz LE, Hubner C, Riebel T, Komen W et al. Myostatin mutation associated with gross muscle hypertrophy in a child. New Engl J Med. 2004;350(26):2682-8.

Mosher DS, Quignon P, Bustamante CD, Sutter NB, Mellersh CS, Parker HG et al. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genetics. 2007;3(5):e79.

Dschietzig TB. Myostatin - From the Mighty Mouse to cardiovascular disease and cachexia. Clin chim acta. 2014;433:216-24.

Ishida J, Konishi M, Saitoh M, Anker M, Anker SD, Springer J. Myostatin signaling is up-regulated in female patients with advanced heart failure. Int J Cardiol. 2017;238:37-42.

Freeman LM, Rush JE, Cunningham SM, Yang VK, Bulmer BJ. Pilot study of a myostatin antagonist in dogs with cardiac cachexia. J Vet Cardiol. 2015;17(3):210-5.

Sever S, White DL, Garcia JM. Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review. Endocr Relat Cancer. 2016;23(9):R393-409.

DeBoer MD. Emergence of ghrelin as a treatment for cachexia syndromes. Nutrition. 2008;24(9):806-14.

Lund LH, Williams JJ, Freda P, LaManca JJ, LeJemtel TH, Mancini DM. Ghrelin resistance occurs in severe heart failure and resolves after heart transplantation. Eur J Heart Fail. 2009;11(8):789-94.

Vodnik M, Strukelj B, Lunder M. Ghrelin Receptor Ligands Reaching Clinical Trials: From Peptides to Peptidomimetics; from Agonists to Antagonists. Horm Metab Res. 2016;48(1):1-15. 99. Molfino A, Amabile MI, Rossi Fanelli F, Muscaritoli M. Novel therapeutic options for cachexia and sarcopenia. Exp Opin Biol Ther. 2016;16(10):1239-44.

Nagaya N, Uematsu M, Kojima M, Ikeda Y, Yoshihara F, Shimizu W et al. Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation. 2001;104(12):1430-5.

Deboer MD, Zhu X, Levasseur PR, Inui A, Hu Z, Han G et al. Ghrelin treatment of chronic kidney disease: improvements in lean body mass and cytokine profile. Endocrinol. 2008;149(2):827-35.

Palus S, von Haehling S, Doehner W, Datta R, Zhang J, Dong JZ et al. Effect of application route of the ghrelin analog BIM-28131 (RM-131) on body weight and body composition in a rat heart failure model. Int J Cardiol. 2013;168(3):2369-74.

Nagaya N, Moriya J, Yasumura Y, Uematsu M, Ono F, Shimizu W et al. Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation. 2004;110(24):3674-9.

Temel JS, Abernethy AP, Currow DC, Friend J, Duus EM, Yan Y et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol. 2016;17(4):519-31.

Currow D, Temel JS, Abernethy A, Milanowski J, Friend J, Fearon KC. ROMANA 3: a phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia. Ann Oncol. 2017;28(8):1949-56.

Zollers B, Rhodes L, Rausch-Derra LC, Armintrout G, Bell M. Safety of the ghrelin agonist, capromorelin, administered daily to beagle dogs for 1 year. J Vet Intern Med. 2015;29(4):1217.

Zollers B, Huebner M, Armintrout G, Rausch-Derra LC, Rhodes L. Evaluation of the safety in dogs of long-term, daily oral administration of capromorelin, a novel drug for stimulation of appetite. J Vet Pharmacol Ther. 2017;40(3):248-55.

Zollers B, Rhodes L, Heinen E. Capromorelin oral solution (ENTYCE(R)) increases food consumption and body weight when administered for 4 consecutive days to healthy adult Beagle dogs in a randomized, masked, placebo controlled study. BMC Vet Res. 2017;13(1):10.

Zollers B, Rhodes L, Smith RG. Capromorelin increases food consumption, body weight, growth hormone, and sustained insulin-like growth factor 1 concentrations when administered to healthy adult Beagle dogs. J Vet Pharmacol Ther. 2017;40(2):140-7.

Zollers B, Wofford JA, Heinen E, Huebner M, Rhodes L. A Prospective, Randomized, Masked, Placebo-Controlled Clinical Study of Capromorelin in Dogs with Reduced Appetite. J Vet Intern Med. 2016;30(6):1851-7.

Zollers B, Allen J, Kennedy C, Rhodes L. Capromorelin, an orally active ghrelin agonist, caused sustained increases in IGF-1, increased food intake and body weight in cats. J Vet Intern Med. 2015;29(4):1219.

Zollers B, Allen J, Kennedy C, Rhodes L. Safety of the ghrelin agonist, capromorelin, administered daily to cats for 91 days at an oral dose of 6 mg/kg. J Vet Intern Med. 2015;29(4):1219.

Mehra MR, Lavie CJ, Ventura HO, Milani RV. Fish oils produce anti-inflammatory effects and improve body weight in severe heart failure. J Heart Lung Transplant. 2006;25(7):834-8.

Smith GI, Julliand S, Reeds DN, Sinacore DR, Klein S, Mittendorfer B. Fish oil-derived n-3 PUFA therapy increases muscle mass and function in healthy older adults. Am J Clin Nutr. 2015;102(1):115-22.

Smith CE, Freeman LM, Rush JE, Cunningham SM, Biourge V. Omega-3 fatty acids in boxer dogs with arrhythmogenic right ventricular cardiomyopathy. J Vet Intern Med. 2007;21(2):265-73.

Freeman LM. Beneficial effects of omega-3 fatty acids in cardiovascular disease. J Small Anim Pract. 2010;51(9):462-70.

Ogilvie GK, Fettman MJ, Mallinckrodt CH, Walton JA, Hansen RA, Davenport DJ et al. Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma: a double-blind, randomized placebo-controlled study. Cancer. 2000;88(8):1916-28.

Ogilvie GK. Effects of fish oil, arginine and doxorubricin chemotherapy on remission and survival tie in dogs with lymphoma: A double blind, randomized controlled study. Proc 18th American College of Veterinary Internal Medicine Forum, Seattle, WA. 2000:766.

Brown SA, Brown CA, Crowell WA, Barsanti JA, Allen T, Cowell C et al. Beneficial effects of chronic administration of dietary omega-3 polyunsaturated fatty acids in dogs with renal insufficiency. J Lab Clin Med. 1998;131(5):447-55.

Brown SA, Brown CA, Crowell WA, Barsanti JA, Kang CW, Allen T et al. Effects of dietary polyunsaturated fatty acid supplementation in early renal insufficiency in dogs. J Lab Clin Med. 2000;135(3):275-86.

Plantinga EA, Everts H, Kastelein AM, Beynen AC. Retrospective study of the survival of cats with acquired chronic renal insufficiency offered different commercial diets. Vet Rec. 2005;157(7):185-7.

Bauer JE. Therapeutic use of fish oils in companion animals. J Am Vet Med Assoc. 2011;239(11):1441-51.

Konishi M, Ishida J, von Haehling S, Anker SD, Springer J. Nutrition in cachexia: from bench to bedside. J Cachexia Sarcopenia Muscle. 2016;7(2):107-9.

Borg JJ, Anker SD, Rosano G, Serracino-Inglott A, Strasser F. Multimodal management as requirement for the clinical use of anticachexia drugs - a regulatory and a clinical perspective. Curr Opin Support Palliative Care. 2015;9(4):333-45.


Refbacks

  • There are currently no refbacks.