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Cardiovascular Disease in Hamsters: Review and Retrospective Study
AEMV Forum
Cardiovascular Disease in Hamsters: Review and Retrospective Study Robert E. Schmidt, DVM, PhD, DACVP, Drury R. Reavill, DVM, Dip. ABVP, (Avian), DACVP
Abstract A considerable literature on hamsters and their diseases is available, primarily pertaining to laboratory hamsters, and more particularly to the Syrian (golden) hamster (Mesocritecus auratus). Because hamsters sold in the pet trade are essentially of similar strains, this article will review diseases and lesions of the heart reported in hamsters and will present data on conditions submitted to our diagnostic pathology service. The literature review is not meant to be comprehensive but will cover commonly reported natural disease conditions and a few experimentally produced diseases. Copyright 2007 Elsevier Inc. All rights reserved. Key words: hamster; heart disease; coronary arteries; aortic valves
A
number of congenital heart problems have been reported in the hamster. The condition of coronary arteries and aortic valves was studied in 552 Syrian hamsters belonging to a single family.1 In 178 hamsters, the aortic valve was bicuspid, rather than normal tricuspid. In 138 specimens, 54 with normal aortic valves and 84 with bicuspid aortic valves (anomalies in the origin of the coronary arteries) were classified into three morphologic types: left coronary artery from the pulmonary trunk (36 cases), single right coronary artery (84 cases), and left coronary artery from the dorsal aortic sinus (18 cases). Another study indicated that in the Syrian hamster, the morphogenetic mechanisms involved in the formation of congenital anomalous aortic valves and anomalies in the origin of the left coronary artery, respectively, are strongly related from an etiological viewpoint.2 Solitary coronary ostium was detected in 130 cases found in a database consisting of 1202 internal casts of the heart, great arterial trunks, and coronary arteries.3 In 21 (16.2%) cases, the solitary ostium was located in the left aortic sinus. In a further 58 (44.6%) cases, it was in the right aortic sinus. In the remaining 51 (39.2%) cases, the ostium
was in the right side of the ventral aortic sinus of a bicuspid aortic valve. When a sole coronary ostium becomes established in the aortic root, an anomalous coronary arterial tree develops. Cardiomyopathy has been noted in certain Syrian hamster lines for many years.4 The most thoroughly studied is skeletal and cardiac dystrophy in the BIO 14.6 strain. It is a progressive, autosomal recessive condition with onset at 60 to 120 days. Affected hearts are progressively affected and grossly are round with flaccid ventricles. The natural history of the disease of the dilated strain Bio TO-2 of cardiomyopathic hamsters (CMH) has not been totally characterized, however. These hamsters progressively develop an alteration of cardiac function leading to decreased mean arterial pressure and musculocutaneFrom the Zoo/Exotic Pathology Service, Greenview, CA 96037 USA. Address correspondence to: Dr. Robert E. Schmidt, Zoo/Exotic Pathology Service, PO Box 267, Greenview, CA 96037. E-mail: [email protected] © 2007 Elsevier Inc. All rights reserved. 1557-5063/07/1601-$30.00 doi:10.1053/j.jepm.2006.11.009
Journal of Exotic Pet Medicine, Vol 16, No 1 ( January), 2007: pp 49-51
49
50 ous blood flow associated with cardiac remodeling that includes atrial hypertrophy and left ventricular dilation, wall thinning, and a rise in collagen density.5 Heart anomalies have been experimentally produced in hamsters by treating pregnant females with a variety of compounds. These have been briefly reviewed.6 The two most commonly reported noninfectious conditions of the hamster cardiovascular system are atrial thrombosis7 and calcifying vasculopathy.8 The process of atrial thrombosis has been considered a consumption coagulopathy.9 One study10 found ventricular hypertrophy and valvular thickening and theorized that the pathogenesis was related to localized blood stasis secondary to heart failure. According to Pour et al in 1976,8 calcifying vasculopathy was the most common lesion seen in the cardiovascular system of the hamsters they studied. The mineralization was usually confined to the elastic layers. The aorta and cardiac, renal, and gastric arteries were most severely affected.7 Other noninfectious cardiovascular lesions7 identified in hamsters included cardiomyopathy and myocardial mineralization. The etiology of these conditions was not determined. The functional status of the cardiovascular system in healthy CMHs was assessed throughout their lives by measuring heart weight and fluid in the pleural and peritoneal cavities.11 An index of cardiovascular age was developed. This index showed parallel changes in healthy CMHs with increasing age. It correctly predicted the early death of those hamsters that died before the average death age. Hamsters that lived beyond the average death age had cardiovascular ages younger than the average death age. This index was correlated with histopathological signs of congestive heart failure in both strains of hamsters, as well as with the total amount of pathology found in them. The data suggested that aging, at least in hamsters, may be closely related to the natural development of heart failure, which represents a common end stage of life in both CMHs and very old, supposedly healthy, hamsters.
Infectious Diseases
Schmidt and Reavill
tulus griseus).13 Although cardiovascular lesions are a significant cause of disease in hamsters, they are rarely reported. A case of phlebothrombosis in hamsters caused by Salmonella enteritidis was reported.14 Reports of viral disease affecting the hamster cardiovascular system are limited to experimentally induced conditions.15 Hamsters have been used as models for Chagas’ disease cardiomyopathy16 and experimental schistosomiasis.17
Neoplasms Tumors of the cardiovascular system are infrequently reported. Lymphosarcoma can involve the myocardium,7 and hemangiomas may be seen in a variety of tissues including the heart.18
Other Hamsters Relative to the Syrian hamster, there is a paucity of information regarding cardiovascular disease affecting other hamster species. In Chinese hamsters, cardiac diseases that have been identified include arteriosclerosis, myocarditis, acute and chronic myocardial fibrosis, and auricular thrombosis.19
Retrospective Study Hamsters make up 14.24% of rodent submissions in the files of the Zoo/Exotic Pathology Service. In most cases, the exact type of hamster was not indicated, but most are assumed to be Syrian hamsters. Cardiovascular disease was diagnosed in 14 hamsters (5.6%): 6 females, 6 males, and 2 of unknown sex. The diagnoses are given in Table 1. Suppurative myocarditis was presumed to be most likely due to a bacterial infection. Septic atrial thrombosis was also considered most likely infectious and associated with a valvular infection, but it was similar to the atrial thrombosis reported in the literature, with secondary infection possible.
Bacterial Disease
Discussion
Tyzzer’s disease occurs in Syrian hamsters with variable lesions that include cardiac involvement.12 In Syrian hamsters, gross lesions included multiple white nodules in the heart. Histologically, areas of necrosis were noted, and the causative agent, Bacillus piliformis, was present within myocardial fibers. Heart lesions were not reported in Chinese hamsters (Crice-
Although comprising less than 10% of the final disease diagnoses identified in necropsied hamsters, our database and the literature reports indicate that cardiovascular disease is not uncommon in these animals. One of the reasons for the small cardiovascular dataset in our series is a failure of veterinarians
51
Cardiovascular Disease in Hamsters
Table 1. Histologic Diagnoses of Hamster Heart Disease Sex M M M M M M F F F F
F F
Age
Diagnosis
Unknown 4 mo 4 mo 18 mo 24 mo Unknown Unknown Unknown 6 mo 4 mo
Suppurative myocarditis Suppurative myocarditis Suppurative myocarditis Right ventricular hypertrophy Mineralization Nonsuppurative myocarditis Hemorrhage Suppurative myocarditis Septic mural thrombosis Myodegeneration, nonsuppurative myocarditis, and mineralization Epicarditis and myocarditis Suppurative myocarditis and mineralization Left ventricular hypertrophy Myodegeneration and fibrosis
Unknown Unknown
Unknown Unknown Unknown Unknown
References 1. 2. 3.
4. 5.
6.
7. 8.
to submit whole hearts from hamsters for pathological examination. Heart disease in the hamster can lead to a variety of clinical signs, some of which may be minimal and/or noted over a long period of time. Clinical signs associated with heart disease in hamsters may include pulmonary manifestations as well as lethargy and edema. The overt clinical signs are often nonspecific, making an antemortem definitive diagnosis of cardiovascular disease difficult. Although gross cardiac lesions are often present, they may be minimal and difficult to detect at necropsy. The clinician should keep heart disease in mind as a differential diagnosis for a variety of clinical signs and examine the heart at necropsy. Even if well-defined lesions are not grossly observed, the heart should be submitted for histology. Because of the importance of gross examination of the fresh heart in detecting congenital problems, it should be carefully opened in the direction of the blood flow, starting with the venous return and including examination of the valves in situ. Determining the classification of heart disease is important, particularly if there are other animals present. In the case of congenital (and possibly inherited) conditions, long-term breeding colony management can be addressed. In the case of infectious disease, appropriate treatments and management can be recommended.
9. 10. 11. 12. 13. 14. 15. 16.
17.
18. 19.
Sans-Coma V, Arque JM, Duran AC, et al: Coronary artery anomalies and bicuspid aortic valves in the Syrian hamster. Basic Res Cardiol 86:148-153, 1991 Fernandez MC, Duran AC, Real R, et al: Coronary artery anomalies and aortic valve morphology in the Syrian hamster. Lab Anim 34:145-154, 2000 Duran AC, Fernandez-Gallego T, Fernandez B, et al: Solitary coronary ostium in the aorta in Syrian hamsters. A morphological study of 130 cases. Pathology 14:303-311, 2005 Homburger F: Disease models in Syrian hamsters. Prog Exp Tumor Res 16:69-86, 1972 Goineau S, Pape D, Guillo P, et al: Hemodynamic and histomorphometric characteristics of dilated cardiomyopathy of Syrian hamsters (Bio TO-2 strain). Can J Physiol Pharmacol 79:329-337, 2001 Newcomer CF, Fitts DA, Goldman BD, et al: Experimental biology: other research uses of Syrian hamsters, in Van Hoosier GL Jr, McPherson CW (eds): Laboratory Hamsters, Orlando, FL, Academic Press Inc, pp 264-289, 1987 Schmidt RE, Eason RL, Hubbard GB, et al: Cardiovascular system, in Pathology of Aging Syrian Hamsters. Boca Raton, FL, CRC Press, pp 3-19, 1983 Pour P, Mohr U, Althoff J, et al: Spontaneous tumors and common diseases in two colonies of Syrian hamsters IV. Vascular and lymphatic systems and lesions of other sites. J Natl Cancer Inst 56:963-974, 1976 Dodds WJ, Raymond SL, Moynihan AC, et al: Spontaneous atrial thrombosis in aged Syrian hamsters. II. Hemostasis. Thromb Hemostasis 38:457-464, 1977 McMartin DN: Spontaneous atrial thrombosis in aged Syrian hamsters. I. Incidence and pathology thrombosis hemostasis. 38:447-456, 1977 Ottenweller JE, Tapp WN, Chen TS: Cardiovascular aging in Syrian hamsters: similarities between normal aging and disease. Exp Aging Res 13:73-84, 1987 Zook BC, Huang K, Rhorer RG: Tyzzer’s disease in Syrian hamsters. J Am Vet Med Assoc 17:1833-1836, 1977 Zook BC, Albert EN, Rhorer RG: Tyzzer’s disease in the Chinese hamster (Cricetulus griseus). Lab Anim Sci 27:1033-1035, 1977 Innes JRM, Wilson C, Ross MA: Epizootic Salmonella enteritidis infection causing septic pulmonary phlebothrombosis in hamsters. J Infect Dis 98:133-141, 1956 Sugawara Y, Hirasawa K, Takeda M, et al: Acute infection of encephalomyocarditis (EMC) virus in Syrian hamsters. J Vet Med Sci 53:463-468, 1991 Bilate AM, Salemi VM, Ramires FJ, et al: The Syrian hamster as a model for the dilated cardiomyopathy of Chagas’ disease: a quantitative echocardiographical and histopathological analysis. Microbes Infect 5:1116-1124, 2003 Morgan JS, Groszmann RJ, Rojkind M, et al: Hemodynamic mechanisms of emerging portal hypertension caused by schistosomiasis in the hamster. Hepatology 11:98-104, 1990 Pour P, Althoff J, Saimasi SZ, et al: Spontaneous tumors and common diseases in three types of hamsters. J Natl Cancer Inst 63:797-811, 1979 Benjamin SA, Brooks AL: Spontaneous lesions in Chinese hamsters. Vet Pathol 14:449-462, 1977
Cardiovascular Disease in Hamsters: Review and Retrospective Study Robert E. Schmidt, DVM, PhD, DACVP, Drury R. Reavill, DVM, Dip. ABVP, (Avian), DACVP
Abstract A considerable literature on hamsters and their diseases is available, primarily pertaining to laboratory hamsters, and more particularly to the Syrian (golden) hamster (Mesocritecus auratus). Because hamsters sold in the pet trade are essentially of similar strains, this article will review diseases and lesions of the heart reported in hamsters and will present data on conditions submitted to our diagnostic pathology service. The literature review is not meant to be comprehensive but will cover commonly reported natural disease conditions and a few experimentally produced diseases. Copyright 2007 Elsevier Inc. All rights reserved. Key words: hamster; heart disease; coronary arteries; aortic valves
A
number of congenital heart problems have been reported in the hamster. The condition of coronary arteries and aortic valves was studied in 552 Syrian hamsters belonging to a single family.1 In 178 hamsters, the aortic valve was bicuspid, rather than normal tricuspid. In 138 specimens, 54 with normal aortic valves and 84 with bicuspid aortic valves (anomalies in the origin of the coronary arteries) were classified into three morphologic types: left coronary artery from the pulmonary trunk (36 cases), single right coronary artery (84 cases), and left coronary artery from the dorsal aortic sinus (18 cases). Another study indicated that in the Syrian hamster, the morphogenetic mechanisms involved in the formation of congenital anomalous aortic valves and anomalies in the origin of the left coronary artery, respectively, are strongly related from an etiological viewpoint.2 Solitary coronary ostium was detected in 130 cases found in a database consisting of 1202 internal casts of the heart, great arterial trunks, and coronary arteries.3 In 21 (16.2%) cases, the solitary ostium was located in the left aortic sinus. In a further 58 (44.6%) cases, it was in the right aortic sinus. In the remaining 51 (39.2%) cases, the ostium
was in the right side of the ventral aortic sinus of a bicuspid aortic valve. When a sole coronary ostium becomes established in the aortic root, an anomalous coronary arterial tree develops. Cardiomyopathy has been noted in certain Syrian hamster lines for many years.4 The most thoroughly studied is skeletal and cardiac dystrophy in the BIO 14.6 strain. It is a progressive, autosomal recessive condition with onset at 60 to 120 days. Affected hearts are progressively affected and grossly are round with flaccid ventricles. The natural history of the disease of the dilated strain Bio TO-2 of cardiomyopathic hamsters (CMH) has not been totally characterized, however. These hamsters progressively develop an alteration of cardiac function leading to decreased mean arterial pressure and musculocutaneFrom the Zoo/Exotic Pathology Service, Greenview, CA 96037 USA. Address correspondence to: Dr. Robert E. Schmidt, Zoo/Exotic Pathology Service, PO Box 267, Greenview, CA 96037. E-mail: [email protected] © 2007 Elsevier Inc. All rights reserved. 1557-5063/07/1601-$30.00 doi:10.1053/j.jepm.2006.11.009
Journal of Exotic Pet Medicine, Vol 16, No 1 ( January), 2007: pp 49-51
49
50 ous blood flow associated with cardiac remodeling that includes atrial hypertrophy and left ventricular dilation, wall thinning, and a rise in collagen density.5 Heart anomalies have been experimentally produced in hamsters by treating pregnant females with a variety of compounds. These have been briefly reviewed.6 The two most commonly reported noninfectious conditions of the hamster cardiovascular system are atrial thrombosis7 and calcifying vasculopathy.8 The process of atrial thrombosis has been considered a consumption coagulopathy.9 One study10 found ventricular hypertrophy and valvular thickening and theorized that the pathogenesis was related to localized blood stasis secondary to heart failure. According to Pour et al in 1976,8 calcifying vasculopathy was the most common lesion seen in the cardiovascular system of the hamsters they studied. The mineralization was usually confined to the elastic layers. The aorta and cardiac, renal, and gastric arteries were most severely affected.7 Other noninfectious cardiovascular lesions7 identified in hamsters included cardiomyopathy and myocardial mineralization. The etiology of these conditions was not determined. The functional status of the cardiovascular system in healthy CMHs was assessed throughout their lives by measuring heart weight and fluid in the pleural and peritoneal cavities.11 An index of cardiovascular age was developed. This index showed parallel changes in healthy CMHs with increasing age. It correctly predicted the early death of those hamsters that died before the average death age. Hamsters that lived beyond the average death age had cardiovascular ages younger than the average death age. This index was correlated with histopathological signs of congestive heart failure in both strains of hamsters, as well as with the total amount of pathology found in them. The data suggested that aging, at least in hamsters, may be closely related to the natural development of heart failure, which represents a common end stage of life in both CMHs and very old, supposedly healthy, hamsters.
Infectious Diseases
Schmidt and Reavill
tulus griseus).13 Although cardiovascular lesions are a significant cause of disease in hamsters, they are rarely reported. A case of phlebothrombosis in hamsters caused by Salmonella enteritidis was reported.14 Reports of viral disease affecting the hamster cardiovascular system are limited to experimentally induced conditions.15 Hamsters have been used as models for Chagas’ disease cardiomyopathy16 and experimental schistosomiasis.17
Neoplasms Tumors of the cardiovascular system are infrequently reported. Lymphosarcoma can involve the myocardium,7 and hemangiomas may be seen in a variety of tissues including the heart.18
Other Hamsters Relative to the Syrian hamster, there is a paucity of information regarding cardiovascular disease affecting other hamster species. In Chinese hamsters, cardiac diseases that have been identified include arteriosclerosis, myocarditis, acute and chronic myocardial fibrosis, and auricular thrombosis.19
Retrospective Study Hamsters make up 14.24% of rodent submissions in the files of the Zoo/Exotic Pathology Service. In most cases, the exact type of hamster was not indicated, but most are assumed to be Syrian hamsters. Cardiovascular disease was diagnosed in 14 hamsters (5.6%): 6 females, 6 males, and 2 of unknown sex. The diagnoses are given in Table 1. Suppurative myocarditis was presumed to be most likely due to a bacterial infection. Septic atrial thrombosis was also considered most likely infectious and associated with a valvular infection, but it was similar to the atrial thrombosis reported in the literature, with secondary infection possible.
Bacterial Disease
Discussion
Tyzzer’s disease occurs in Syrian hamsters with variable lesions that include cardiac involvement.12 In Syrian hamsters, gross lesions included multiple white nodules in the heart. Histologically, areas of necrosis were noted, and the causative agent, Bacillus piliformis, was present within myocardial fibers. Heart lesions were not reported in Chinese hamsters (Crice-
Although comprising less than 10% of the final disease diagnoses identified in necropsied hamsters, our database and the literature reports indicate that cardiovascular disease is not uncommon in these animals. One of the reasons for the small cardiovascular dataset in our series is a failure of veterinarians
51
Cardiovascular Disease in Hamsters
Table 1. Histologic Diagnoses of Hamster Heart Disease Sex M M M M M M F F F F
F F
Age
Diagnosis
Unknown 4 mo 4 mo 18 mo 24 mo Unknown Unknown Unknown 6 mo 4 mo
Suppurative myocarditis Suppurative myocarditis Suppurative myocarditis Right ventricular hypertrophy Mineralization Nonsuppurative myocarditis Hemorrhage Suppurative myocarditis Septic mural thrombosis Myodegeneration, nonsuppurative myocarditis, and mineralization Epicarditis and myocarditis Suppurative myocarditis and mineralization Left ventricular hypertrophy Myodegeneration and fibrosis
Unknown Unknown
Unknown Unknown Unknown Unknown
References 1. 2. 3.
4. 5.
6.
7. 8.
to submit whole hearts from hamsters for pathological examination. Heart disease in the hamster can lead to a variety of clinical signs, some of which may be minimal and/or noted over a long period of time. Clinical signs associated with heart disease in hamsters may include pulmonary manifestations as well as lethargy and edema. The overt clinical signs are often nonspecific, making an antemortem definitive diagnosis of cardiovascular disease difficult. Although gross cardiac lesions are often present, they may be minimal and difficult to detect at necropsy. The clinician should keep heart disease in mind as a differential diagnosis for a variety of clinical signs and examine the heart at necropsy. Even if well-defined lesions are not grossly observed, the heart should be submitted for histology. Because of the importance of gross examination of the fresh heart in detecting congenital problems, it should be carefully opened in the direction of the blood flow, starting with the venous return and including examination of the valves in situ. Determining the classification of heart disease is important, particularly if there are other animals present. In the case of congenital (and possibly inherited) conditions, long-term breeding colony management can be addressed. In the case of infectious disease, appropriate treatments and management can be recommended.
9. 10. 11. 12. 13. 14. 15. 16.
17.
18. 19.
Sans-Coma V, Arque JM, Duran AC, et al: Coronary artery anomalies and bicuspid aortic valves in the Syrian hamster. Basic Res Cardiol 86:148-153, 1991 Fernandez MC, Duran AC, Real R, et al: Coronary artery anomalies and aortic valve morphology in the Syrian hamster. Lab Anim 34:145-154, 2000 Duran AC, Fernandez-Gallego T, Fernandez B, et al: Solitary coronary ostium in the aorta in Syrian hamsters. A morphological study of 130 cases. Pathology 14:303-311, 2005 Homburger F: Disease models in Syrian hamsters. Prog Exp Tumor Res 16:69-86, 1972 Goineau S, Pape D, Guillo P, et al: Hemodynamic and histomorphometric characteristics of dilated cardiomyopathy of Syrian hamsters (Bio TO-2 strain). Can J Physiol Pharmacol 79:329-337, 2001 Newcomer CF, Fitts DA, Goldman BD, et al: Experimental biology: other research uses of Syrian hamsters, in Van Hoosier GL Jr, McPherson CW (eds): Laboratory Hamsters, Orlando, FL, Academic Press Inc, pp 264-289, 1987 Schmidt RE, Eason RL, Hubbard GB, et al: Cardiovascular system, in Pathology of Aging Syrian Hamsters. Boca Raton, FL, CRC Press, pp 3-19, 1983 Pour P, Mohr U, Althoff J, et al: Spontaneous tumors and common diseases in two colonies of Syrian hamsters IV. Vascular and lymphatic systems and lesions of other sites. J Natl Cancer Inst 56:963-974, 1976 Dodds WJ, Raymond SL, Moynihan AC, et al: Spontaneous atrial thrombosis in aged Syrian hamsters. II. Hemostasis. Thromb Hemostasis 38:457-464, 1977 McMartin DN: Spontaneous atrial thrombosis in aged Syrian hamsters. I. Incidence and pathology thrombosis hemostasis. 38:447-456, 1977 Ottenweller JE, Tapp WN, Chen TS: Cardiovascular aging in Syrian hamsters: similarities between normal aging and disease. Exp Aging Res 13:73-84, 1987 Zook BC, Huang K, Rhorer RG: Tyzzer’s disease in Syrian hamsters. J Am Vet Med Assoc 17:1833-1836, 1977 Zook BC, Albert EN, Rhorer RG: Tyzzer’s disease in the Chinese hamster (Cricetulus griseus). Lab Anim Sci 27:1033-1035, 1977 Innes JRM, Wilson C, Ross MA: Epizootic Salmonella enteritidis infection causing septic pulmonary phlebothrombosis in hamsters. J Infect Dis 98:133-141, 1956 Sugawara Y, Hirasawa K, Takeda M, et al: Acute infection of encephalomyocarditis (EMC) virus in Syrian hamsters. J Vet Med Sci 53:463-468, 1991 Bilate AM, Salemi VM, Ramires FJ, et al: The Syrian hamster as a model for the dilated cardiomyopathy of Chagas’ disease: a quantitative echocardiographical and histopathological analysis. Microbes Infect 5:1116-1124, 2003 Morgan JS, Groszmann RJ, Rojkind M, et al: Hemodynamic mechanisms of emerging portal hypertension caused by schistosomiasis in the hamster. Hepatology 11:98-104, 1990 Pour P, Althoff J, Saimasi SZ, et al: Spontaneous tumors and common diseases in three types of hamsters. J Natl Cancer Inst 63:797-811, 1979 Benjamin SA, Brooks AL: Spontaneous lesions in Chinese hamsters. Vet Pathol 14:449-462, 1977