JPC SYSTEMIC PATHOLOGY
Signalment (JPC Accession #2307591): 13-year-old female owl monkey (Aotus sp.)
HISTORY: This monkey was found moribund at the bottom of the cage.
Heart, left ventricle: Multifocally, affecting approximately 40% of the myocardium, predominately the papillary muscles, inner aspect of the myocardium and endocardium, there is moderate to marked loss of cardiomyocytes with replacement by hypertrophied fibroblasts and fibrous connective tissue (fibrosis). Remaining myocytes are variably sized and exhibit the following changes: increased diameter (hypertrophy); shrunken, individualized, and surrounded by fibrous connective tissue (atrophy); contain pale granular or vacuolated sarcoplasm (degeneration); or are shrunken with hypereosinophilic sarcoplasm, loss of cross striations and pyknotic nuclei (necrosis). Multifocally, within the epicardium, the subepicardial connective tissue and myocardium, there are low numbers of lymphocytes, plasma cells, macrophages, and rare neutrophils, ectatic lymphatics (edema), and scattered small foci of hemorrhage. Many myocytes contain variable amounts of golden-brown perinuclear pigment (lipofuscin).
Lung: Multifocally, approximately 80% of alveoli are variably filled with mildly increased numbers of macrophages with foamy cytoplasm or intra-cytoplasmic hemosiderin pigment (“heart failure cells”) and few extravasated erythrocytes. Multifocally alveolar septa are thickened up to 50um by congestion, macrophages, eosinophilic finely beaded material (fibrin) and edema.
Lymph node, site not specified: Diffusely, subcapsular and medullary sinuses contain many erythrocytes (draining hemorrhage) and increased numbers of macrophages that exhibit erythrophagocytosis and hemosiderosis.
Trachea: No significant lesions.
Liver: Affecting approximately 70% of the liver parenchyma, there is diffuse, marked centrilobular to midzonal necrosis and hemorrhage with variable retention of architecture. Hepatocytes within affected areas are lost and replaced by, or individualized and widely separated by hemorrhage and fibrin with minimal necrotic debris. There is marked dilation of sinusoids with congestion. Remaining hepatocytes contain few to many variably sized, clear discrete vacuoles (lipid-type vacuolar change/degeneration) and/or fine brown granules in their cytoplasm (lipofuscin, bile, hemosiderin, or copper). There are bile plugs within canaculi (cholestasis) and Kupffer cells within sinusoids which contain brown granular intracytoplasmic pigment (bile or hemosiderin). Multifocally portal areas contain ectatic lymphatics filled with an eosinophilic proteinaceous material (edema).
- Heart, left ventricle: Myocardial loss and atrophy, multifocal to coalescing, marked, with fibrosis, owl monkey (Aotus), non-human primate.
- Lung: Alveolar histiocytosis, diffuse, moderate, with hemosiderosis, congestion and edema.
- Lymph node, site not specified: Draining hemorrhage, diffuse, moderate, with erythrophagocytosis and hemosiderosis
- Liver: Necrosis, centrilobular to midzonal, diffuse, severe, with hemorrhage, hemosiderosis, congestion, edema and lipid-type vacuolar degeneration (chronic passive congestion).
CONDITION: Aotus cardiomyopathy
- Cardiomyopathy is a very common cause of morbidity and mortality in Aotus monkeys (Aotus monkey refers to owl monkey in the genus Aotus)
- Up to 40% of deaths had some evidence of cardiovascular disease (ventricular dilation or left ventricular hypertrophy)
- Concurrent renal disease is often present and is also a common cause of morbidity and mortality in this species
- The association of heart disease and renal disease is suggestive of cardiorenal syndrome which has been described in older humans; in this condition the initial cardiac dysfunction leads to progressive kidney dysfunction; likewise, the continuing kidney dysfunction contributes to further decline of the heart
- A recent study (Vet Pathol 2016) indicated that in aged chimpanzees, as cardiac fibrosis increased, there was a corresponding increase in the amount of glomerulosclerosis and tubulointerstitial fibrosis
- Suspected mechanisms include captivity-induced hypertension, renal-induced hypertension, and heredity
TYPICAL CLINICAL FINDINGS:
- Clinical signs vary; often none are observed prior to death
- Ascites, dyspnea, mouth breathing, reduced exercise tolerance, subcutaneous edema and hepatomegaly
- Some monkeys exhibit paralysis (partial or complete) from secondary thromboembolic disease
- Although cardiac troponins are useful markers of cardiac damage in many species, they may not be reliable indicators of myocardial disease in the owl monkey
- Serum concentrations of CK, AST, and LDH in owl monkeys with proteinuria are good screening tests for the presence of sub-clinical cardiac disease
TYPICAL GROSS FINDINGS:
- Mild to severe hypertrophy of the left ventricular free wall and interventricular septum; pale streaks in the myocardium
- Occasionally dilative cardiomyopathy and pericardial effusion
- Pulmonary congestion and edema
- Chronic passive congestion of the liver, centrilobular necrosis (nutmeg liver)
- Subcutaneous edema (especially the eyelids, muzzle, and bottle jaw); ascites, hydrothorax
- If concurrent renal disease is present, the renal surface is pitted and rough with small white foci present on the capsular and cut surface
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Histopathologic findings in the heart vary from focal areas of necrosis to diffuse interstitial fibrosis depending on the stage of disease
- Myofiber atrophy and loss; remaining myofibers disorganized with loss of linear organization
- Pulmonary changes include alveolar histiocytosis with erythrophagocytosis and hemosiderosis, edema, foamy macrophages, and congestion
- Hepatic changes include congestion, centrilobular to midzonal necrosis, and vacuolar degeneration of hepatocytes
- Renal changes include glomerular hypercellularity, dilated renal tubules, diffuse interstitial fibrosis, and a variable mononuclear cell infiltrate
ADDITIONAL DIAGNOSTIC TESTS:
- Echocardiography, radiographs, and electrocardiography
- Left ventricular diameter and ejection fraction the best measurements for diagnosis
- Cardiac lesions resulting from infectious etiologies may have a similar gross appearance
- Hypertrophic cardiomyopathy (diastolic disorder; most common) (C-M10):
- Inherited form - autosomal dominant in Maine Coon and Radoll cats; mutation in myosin binding protein C3
- This is not to be confused with the concentric cardiac hypertrophy which occurs secondary to hyperthyroidism in cats
- Microscopically, there is myofiber disarray and interstitial fibrosis
- Restrictive cardiomyopathy:
- Results in impaired filling of ventricles during diastole
- AKA “left ventricular endocardial fibrosis” – endocarditis may initiate the lesion
- Microscopically, there is thickening of the endocardium and mural thrombi
- Dilated cardiomyopathy: secondary to taurine deficiency
- Arrythmogenic right ventricular cardiomyopathy (ARVC)-like syndrome: right ventricular inflammation, necrosis, atrophy, fibrosis and replacement with adipose tissue
- Excessive moderator bands (AKA false tendons):
- Probably a congenital defect
- Results in left sided heart failure because the bands connect the papillary muscle to the interventricular septum
- Microscopically, the moderator bands are composed of Purkinje cells, mature collagen, and an endothelial lining
- Dilated cardiomyopathy:
- Giant and large breed dogs affected (St. Bernard, Irish Wolfhound, Estrela Mountain dogs, Great Dane)
- Suspect it has a genetic basis, but there have been no cytoskeletal genes identified as the cause
- Other possible causes: carnitine deficiency; taurine deficiency; hypothyroidism
- Results in congestive heart failure
- 2 microscopic forms:
- Fatty infiltration-degenerative type
- Attenuated wavy fiber type
- ARVC in dogs is a variant of DCM:
- Boxer dogs (may be due to deletion in the striatin gene)
- Right ventricular myocyte loss and replacement with fibroadipose tissue
- Hypertrophic cardiomyopathy: less common than DCM in dogs
- Canine X-linked muscular dystrophy:
- Golden retrievers are model of human disease
- Develop Duchenne cardiomyopathy
- Causes cardiac insufficiency from extensive subepicardial fibrosis
- Cardiomyopathy also reported in squirrel monkeys, common marmosets, and cynomologous macaques
- Spontaneous hypertension reported as a cause of dilated cardiomyopathy in wooly monkeys
- Vitamin E deficiency reported to cause cardiomyopathy in gelada baboons and other primates
- Cardiovascular disease is the leading cause of death in captive great apes, with fibrosing cardiomyopathy (idiopathic cardiomyopathy, interstitial myocardial fibrosis) most frequently diagnosed; develops secondary to hypertension in lowland gorillas, and associated with sudden death and cardiac arrhythmias in chimpanzees; fibrosis also reported in owl monkeys, tamarins, and cynomologous macaques
- Rhesus macaques: Arteriosclerosis is a common background finding that increases with age in rhesus macaques & there is a strong association between arteriosclerosis and hypertension and diabetes; degenerative and fibrosing cardiomyopathy also increases with age recent study of rhesus macaques showed high risk (46%) of sudden death associated with idiopathic concentric hypertrophy of the left ventricle
- Cardiomyopathy of undetermined origin reported in African grey parrots
- Chilton J, Wilcox A, Lammey M, Meyer D. Characterization of a cardiorenal-like syndrome in aged chimpanzees (Pan troglodytes). Vet Pathol. 2016;53(2):417-424.
- Gozalo AS, Chavera A, Montoya EJ, Takano J, Weller RE. Relationship of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and proteinuria to cardiomyopathy in the owl monkey (Aotus vociferans). J Med Primatol. 2008;37 Suppl 1:29-38.
- Juan-Salles C, Soto S, Garner MM, Montesinos A, Ardiaca M. Congestive heart failure in 6 African grey parrots (Psittacus erithacus). Vet Pathol. 2011; 48(3):691-7.
- Lowenstein LJ, McManamon R, Terio KA. Comparative pathology of great apes: bonobos, chimpanzees, gorillas, and orangutans. Vet Pathol. 2016;53(2):250-76.
- Rajendra RS, Brady AG, Parks VL, Massey CV, Gibson SV, Abee CR. The normal and abnormal owl monkey (Aotus) heart: looking at cardiomyopathy changes with echocardiography and electrocardiography. J Med Primatol. 2010; 39:143-150.
- Reader, JR, Canfield DR, et al. Left Ventricular Hypertrophy in rhesus macaques (Macaca mulatta) at the California National Primate Research Center (1992-2014). Comp Med. 2016;66(2):162-9.
- Rishniw MR, Schiavetta AM, Johnson TO: Cardiomyopathy in captive owl monkeys. Comp Med. 2005;55:162-168.
- Robinson WF, Robinson NA. Cardiovascular system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 3. 6th ed. St. Louis, MO: Elsevier; 2016:46-49.
- Sassevlle VG, Hotchkiss CE, Levesque PC, Mankowski JL. Hematopoietic, cardiovascular, lymphoid, and mononuclear phagocyte systems of nonhuman primates. In: Abee CR, Mansfield K, Tardiff S, Morris T, eds. Nonhuman Primates in Biomedical Research Vol 2: Diseases. 2nd ed. Waltham, MA: Elsevier; 2012:372.
- Simmons HA. Age-associated pathology in rhesus macaques (Macaca mulatta). Vet Pathol. 2016;53(2):399-416.
- Weller RE. Infectious and noninfectious diseases in owl monkeys. In: Baer JF, Weller RE, Kakoma I, eds. Aotus: The Owl Monkey. San Diego, CA: Academic Press; 1994: 193-195.