Introduction

Cardiovascular disease in small exotic mammals is anecdotally common, but clinical reports of diagnosis and treatment of disease are rare. This review focuses on known causes of cardiovascular disease in the small exotic mammal. Normal physiology, as it differs from the dog and cat will also be highlighted. Cardiomyopathy, dirofilariasis, atrial thrombosis, and other acquired and congenital cardiac and vascular diseases of ferrets, rabbits, rodents, hedgehogs, sugar gliders, raccoons, opossums and skunks will be reviewed. Neoplastic diseases will not be included. Expected clinical signs and diagnostic and treatment options, including a formulary is provided for these species. This review is intended to stimulate the exotic mammal practitioner to diagnose, treat and report cases of cardiovascular disease in these species. Little information in this article is new, however, the reader may find new information and resources as some of these species were studied anatomically and physiologically in the 1970s. This review will also point out the dearth of baseline information available for some of these species.

Cardiovascular Diseases of the Ferret

The normal ferret heart rate is rapid and has a pronounced sinus arrhythmia associated with respiration. The relatively caudally placed heart in the tubular, elongate thorax facilitates safe venipuncture of the cranial vena cava but dictates auscultation between the 6th to 8th ribs rather than in the axilla. Cardiovascular disease is an important differential to consider when presented with a downer or "flat out" ferret. Clinical signs of cardiac disease in ferrets include respiratory, cardiac and generalized signs. Inappetence, weight loss, lethargy, and posterior paresis (loss of the ferret "squink") are common general clinical signs. Cough, emesis, ascites, and dyspnea and syncopal episodes are also common presenting complaints of owners with ferrets suffering cardiovascular disease. Cardiovascular diseases reported in the ferret include dilated and hypertrophic cardiomyopathy, dirofilariasis, valvular disease and myocarditis. Management of congestive heart failure includes administration of oxygen, diuretics, and angiotensin converting enzyme inhibitors. Digoxin therapy is recommended with dilated cardiomyopathy. Third degree atrioventricular block and pacemaker implantation in the ferret have been reported.²² Heartworm prevention is recommended for ferrets. Treatment of heartworm positive ferrets includes corticosteroid administration and cage confinement. Adverse effects have been reported with melarsomine injections.² Heart worms have been successfully surgically removed from the heart of a ferret with caval syndrome at Texas A&M University. Important clinical rule-outs for cardiorespiratory disease secondary to systemic disease in the ferret include lymphoma, distemper virus, or influenza virus infection. Ferrets may also suffer vascular disease from adrenal or other tumor encroachment upon the vena cava or other vasculature.

Cardiovascular Diseases of the Rabbit

Although rarely documented, cardiovascular diseases of the pet rabbit occur and may be on the increase as rabbits increase in numbers as long lived household pets.⁴⁰ Important comparative aspects of cardiovascular physiology of rabbits include that their tricuspid valves are actually bicuspid, that coronary arterial circulation is limited in this species which may predispose them to myocardial ischemia, and that the rabbit sinoatrial node is a relatively small group of pacemaker cells. There is some normal variation in the major vessels of this species.⁶³ The aortic nerve of the rabbit appears to respond only to chemoreceptors not baroreceptors and the pulmonary artery and associated branches are heavily muscular. The aorta of the rabbit has a rhythmic neurogenic contraction, timed with the pulse wave. Rabbit myocardium contains relatively high concentrations of sodium and calcium; administration of extracellular calcium may cause premature ventricular contraction.⁴

Congestive heart failure, congenital heart disease, myocardial disease, valvular and vascular disease all occur in rabbits.³⁵ Congenital cardiac diseases in rabbits include ventricular septal defect, atrial septal defect and valvular cysts.⁶³ Giant breed rabbits may be more prone to dilated cardiomyopathy.²⁵ Vitamin E deficiency in rabbits causes muscular dystrophy and also affects the myocardium. Infectious causes of cardiac disease in rabbits include viral, bacterial, and protozoal pathogens. In clinical medicine, reports of infectious causes of rabbit cardiac disease have been limited to Pasteurella multocida, Staphylococcus spp., Salmonella spp., Streptococcus viridans, Coronavirus and Encephalitozoon cuniculi. Idiopathic cardiac diseases reported in the rabbit include dilated and hypertrophic cardiomyopathy and mitral and bicuspid valve insufficiency. Administration of alpha agonist anesthetics such as detomidine and xylazine has resulted in cardiac disease in this species as has the experimental administration of doxorubicin; avoid administration of these drugs to rabbits.

Stress and increasing age are important factors in the incidence of cardiac disease in the rabbit. Catecholamines cause sustained coronary vessel constriction in the rabbit resulting in ischemic cardiomyopathy. Similarly, chronic stress based on intermittent crowding of rabbits results in dilated cardiomyopathy. Arteriosclerosis and aortic and other vessel mineralization, and atherosclerosis occur on older rabbits resulting in vascular compromise. These diseases may occur spontaneously or secondary to hypercalcemia or hyperlipemia, respectively.

Clinical signs of cardiovascular disease in the rabbit may be more difficult to assess in this prey species. Poor body condition and signs referable to the respiratory system such as dyspnea, open mouth breathing, elbow abduction, sternal recumbency, neck extension, reluctance to move, abnormal lung sounds or lack of respiratory sounds may indicate cardiovascular compromise in the rabbit. Vascular and cardiac clinical abnormalities may be similar to those of the small companion mammal. In the female rabbit, jugular distension may be obscured by the dewlap but ventral abdominal veins may also be assessed. The ears serve as a rabbit cardiovascular barometer and are less objectionable to assess in the rabbit patient. Peripheral pulse may be assessed in the auricular artery with palpation, pulse oximetry or Doppler probe. Venous refill time and perfusion may also be readily assessed in the lightly pigmented rabbit patient. Exophthalmos may be another sign of severe venous congestion. Heart rate and rhythm should be assessed; most rabbits have a sinus rhythm on auscultation and do not normally have a sinus arrhythmia at presentation.

Cardiovascular Diseases of the Rodent

Based on literature review and clinical practice, gerbils, hamsters, guinea pigs, chinchillas and prairie dogs can develop cardiovascular disease. Rats and mice appear, overall, less prone to cardiac disease. Common cardiovascular diseases vary based on the species.

A recent pathology review of pet hamsters (Mesocricetus auratus) indicated a 6% incidence of cardiac disease, although this may be an underestimate based on lack of submission of the heart in many cases.⁴⁷ Noninfectious diseases of pet and laboratory hamsters include a variety of congenital abnormalities, cardiomyopathy, atrial thrombosis, calcifying vasculopathy, and myocardial mineralization. Tyzzer's disease (Bacillus piliformis) and Salmonella enteriditis can also cause cardiovascular disease in the hamster. Hamster incidence of atrial thrombosis is up to 73% in some laboratory strains. Androgens protect from heart disease in the hamster; thus female hamsters tend to suffer cardiovascular disease earlier (~ 13.5 m) than males (~ 21.5 m). Neutering male hamsters removes this effect. Cardiomyopathy is also common in the aged (> 1.5 y) hamster. In the laboratory setting, both dilatative and cardiomyopathic types of cardiomyopathy occur in certain hamster strains and are related to defects in the same gene.^44,45 Clinical signs of cardiovascular disease in the hamster may be nonspecific but include cold extremities, lethargy, anorexia and tachypnea. In other hamster species, less information is available; the Chinese hamster (Cricetulus griseus), may suffer arteriosclerosis, myocarditis, myocardial fibrosis and auricular thrombosis.⁴⁷

Prairie dogs 3–4 years of age may develop dilated cardiomyopathy.¹⁹ Clinical signs include dyspnea, lethargy and anorexia. Odontoma, pneumonia and obesity must be assessed as rule-outs or complicating factors. Treatment may be unrewarding; a nutritional etiology is proposed.

Chinchilla cardiovascular disease may be common, based on practitioner anecdotal reports.³² Apparently, "normal" chinchillas have cardiac murmurs during routine physical examination. Cardiomyopathy has been reported in two young black velvet female chinchillas. Ventricular septal defect and tricuspid regurgitation have also been reported in this species.¹³ Acute death of a related chinchilla may also have been due to cardiac disease. Appropriate diagnostics are warranted in any chinchilla with cardiac abnormalities.

Guinea pigs are noted for their "spectacular" collateralization of their coronary arteries making them unlikely to develop myocardial infarction. Guinea pigs are a preferred species for the studies of human cardiac disease based on their docile nature and ease of obtaining ECG recordings which mimic that of man.²³ The guinea pig heart sound normally consists of the standard two sounds of lub (louder)/dub (softer) however it may be normally preceded by a 4th heart sound corresponding to atrial contraction.⁵² The guinea pig heart normally lies on the midline and extends from the second to the fourth intercostal space.¹¹ The lumen of the right ventricle of the guinea pig contains a moderator band. Guinea pigs may normally have up to three renal arteries.⁵² Cardiovascular diseases reported in the guinea pig include cardiomyopathy, pericardial effusion, and metastatic mineralization.¹⁴ Dyspnea, tachypnea, pale mucous membranes and acute onset of weakness have been reported as clinical signs of cardiac dysfunction in the guinea pig.¹⁴

Cardiovascular Diseases of the Hedgehog and Sugar Glider

Incidence of cardiovascular disease in the African Hedgehog (Atalerix albiventris) approaches 40%.³⁹ Geriatric males are more likely to have cardiac disease but reports of affected animals include those as young as one year of age. Acute death may occur but many animals exhibit clinical disease such as heart murmur, moist rales, dyspnea, dehydration, weight loss, and lethargy. Cardiomegaly, hepatomegaly, pulmonary edema and/or congestion, hydrothorax, ascites, and pulmonary or renal infarcts are common gross necropsy findings.^3,39 Possible etiologies of cardiac disease in the hedgehog include diet, toxin, stress, and genetics.

Cardiovascular Diseases of the Skunk, Opossum, and Raccoon

Most reports of cardiovascular disease in the skunk (Mephitis mephitis), opossum (Didelphis virginiana) and raccoon (Procyon lotor) are limited to experimental models, wildlife necropsies, and anecdotal mention. Cardiomyopathies are anecdotally common in these animals when kept in captivity, likely based on the resultant obesity.^15,27,29 However, no current clinical report of treatment of cardiovascular in these species was found by the author.

In the experimental setting, the opossum is a model for endocarditis and naturally occurring endocarditis and septicemia have also been reported.^{30,33,42,49,50,60} The layman's term "crispy ear" is given to a disease, also called dermal septic necrosis, affecting the ears and tail tips of affected opossums which have clinical signs of septicemia and necrosis of the affected areas. The etiology of this apparently vascular disease has not been scientifically investigated. The opossum has also been used as a scientific model for investigation of systemic hypertension.²¹

Trypanosoma cruzi infection occurs in skunks, raccoons and opossums.^12,38,42,43 In experimental infection of the skunk, animals showed minimal clinical signs but evidenced chronic granulomatous myocarditis.¹² Raccoons infected with this organism in Georgia appeared to suffer little cardiovascular pathology.³⁸ Infection prevalence of trypanosomiasis among North American wildlife is highest among raccoons(16%) and opossums(38%).²⁸ A single case of cor pulmonale and cardiac failure has been reported in an adult male spotted skunk (Spilogale putorius) which died. No treatment or diagnostics specific to cardiovascular disease were performed in this skunk, which evidenced signs of dyspnea, anorexia, lethargy and dried nasal exudates and had a history of tooth abscessation.

Immature Dirofilaria immitis were found naturally occurring in one raccoon.⁵³ Experimental inoculation of raccoons suggests, and additional data from wild raccoon supports the hypothesis that raccoons are not particularly susceptible to Dirofilaria immitis infection.^8,41,53,59 The susceptibility of skunks and opossums to Dirofilariasis has not been definitively established but they are thought to be susceptible.¹⁵

Diagnosis of Cardiovascular Disease in the Small Exotic Mammal

Assessment of the cardiovascular system can be challenging, especially in the more diminutive species. In my hands, careful observation during the exam along with administration of blow by oxygen can be rewarding. Observation of the cardiac impulse is recommended both by auscultation and by placement of the finger on the chest or by assessment with Doppler probe to make cardiac function sounds more audible. Perfusion may be assessed by observation of the feet, tail and ears for color and temperature. Make careful note of baseline heart rate and respiratory rate of the patient on entry to later facilitate the patient response to therapy. ECG reference ranges have been obtained on mice and other small quadrupeds noninvasively via placement of the feet on embedded electrodes.⁹ Diagnostics for use in cardiovascular disease of the small exotic mammal can be adapted from the companion mammal with knowledge of normal physiology of the species at hand.

ECG

Normal ECG tracing values have been reported for the ferret, rabbit, guinea pig, raccoon, and opossum

(Table 1).^{4,5,10,40,52,58}

The cardiac waveform of the ferret closely resembles that of the dog, while the shape of and size of the heart more closely resembles that of the cat.⁵ Normal values of the anesthetized ferret ECG have been reported; positioning and age of the ferret affect the ECG recording. Ferrets younger than 6 months have a higher heart rate than older ferrets.

Important contrasts of the ECG of normal rabbits from that of the cat or dog include a pointed P wave in some rabbit breeds, peaked T waves, and a relatively long ST segment attributed to a diet high in potassium and low in sodium.⁴⁰ The guinea pig electrocardiogram tracing more closely mimics that of humans when compared with other lab rodents. The guinea pig's attitude has provided us with unrestrained electrode measurements as this animal will freely stand on a plate electrode to obtain tracings.⁵²

The opossum ECG has been studied based on their use as a research model. Heart rate and ECG wave configurations, intervals and amplitudes are not affected by death feigning in the opossum.¹⁸ ECG tracing measurements from 10 apparently healthy wild caught opossums which were anesthetized in right lateral recumbency are available (Table 1).⁵⁸ Gender and positioning did not affect ECG recordings in this species. Sinus respiratory arrhythmia was present in the lightly anesthetized or unanesthetized opossums. The P wave of the opossum may be positive or negative in Lead II. Anesthetized raccoons have similar QRS vector orientation to that of the dog but low QRS amplitude similar to cats.²⁴

Table 1. Reference values for ECG parameters in small exotic mammals.*

* Most animals anesthetized and in right lateral recumbency, Lead II
** Range adapted from lead AvF

Radiographs

In the normal ferret, the heart shadow should be raised slightly above the sternum by a fat encased ligament.¹⁷ Sternal contact of the ferret heart shadow on the lateral view connotes cardiac enlargement.

Modified vertebral heart score may also be used to assess ferret heart size.⁵⁵ Other easily identifiable abnormalities of the ferret radiograph associated with heart disease include pleural effusion, pulmonary edema which appears as a patchy interstitial or alveolar pattern, pulmonary venous congestion, ascites, or hepatomegaly and splenomegaly.

In the normal rabbit, the thymus persists into adulthood and remains large throughout the life of the rabbit making it readily visible in the cranial thorax. The thymus forms a cranial "cap" for the heart which points toward the thoracic inlet.⁵¹ The heart is located from ribs 3–6 and occupies a relatively large area of the thoracic cavity.²⁵ The heart may have a considerable amount of pericardial fat in the obese rabbit which may be visible as a soft tissue low density object superimposed over the cardiac apex.²⁰ The lung fields are relatively small and surround a relatively wide cranial mediastinum.²⁰ The aorta and caudal vena cava are normally visible as are pulmonary vessels.²⁵ Normal anatomic variation of the major vessels occur in this species.⁶³ The tracheal carina occurs at the 4th or 5th intercostal space. Cardiomegaly should be considered if the heart is beyond 2.5–3 rib spaces wide on the lateral view.⁴⁰ Abnormal calcification of the aorta may be best visualized on the lateral view. Hydrothorax has similar hallmarks in this species as other companion mammals.²⁰

Atlases are available for normal reference for rodents and other small mammals.^20,51 In the guinea pig the heart is rather cranially placed and has a ventrocranial inclination; this species also normally has a rather wide mediastinum.²⁰ Cardiogenic edema may be evident via increased pulmonary density and tracheal elevation due to cardiac enlargement may occur.²⁰ On radiographic images of the normal Syrian hamster, the apex of the heart points caudoventrally and to the left.²⁰

In the hedgehog, normal radiographic cardiac size or ultrasonographic parameters have not yet been reported. However common radiographic findings associated with cardiac disease in these species generally mimic those of small companion animals: pleural edema, pleural effusion, aerophagia or tracheal elevation.

In the mouse and rat, the heart silhouette can only be distinguished caudally from the lung lobes.⁵¹ The rat has a relatively wide cranial mediastinum as well.

Ultrasound

In the small exotic mammal, ultrasound may be most useful to determine the type of cardiac dysfunction as well as the presence of a mass, dirofilariasis or lung consolidation. Ultrasonographic parameters of normal subjects have been determined for the mouse, Syrian hamster, rabbit, guinea pig, ferret and chinchilla (Table 1). In the chinchilla, mouse and ferret, anesthesia and type of anesthetic affect ultrasonographic parameters.^32,56,57,61 On ultrasonography, a fractional shortening of < 25% has been reported as consistent with cardiac dysfunction in the hedgehog.²⁶ Normal ultrasonographic parameters have not been determined for the skunk, raccoon, opossum, prairie dog, grey squirrel or sugar glider.

Table 2. Reference ultrasonographic measurements of small exotic mammals.⁺

+ range derived from mean +/-1 SD, animals anesthetized in most instances
LVID - Left ventricular internal diameter; LVPW - left ventricular posterior wall; IVS - Internal ventricular septum
LA - left atrium; AO - aorta; HR - heart rate; s - systolic; d - diastolic

Other Diagnostics

Appropriate serology for infectious disease which may affect these species such as pasteurellosis, trypanosomiasis and dirofilariasis may be used in these species. In the author's hands, serologic detection of heartworms in ferrets via an antigen test has been a successful antemortem diagnostic based on necropsy and ultrasonographic findings.

Thoracocentesis and or pleurocentesis are diagnostically useful especially in ruling out infectious and neoplastic causes of effusion. The technique for ferret thoracocentesis differs slightly from the companion mammal based on the relatively caudal position of the heart.⁶² The needle is inserted at the 9th or 10th intercostals space, immediately cranial to the rib, to remove effusion; thoracic ultrasonography is recommended to guide this process.⁶²

Treatment of Cardiovascular Disease in the Small Exotic Mammal

Treatment of cardiovascular disease in the exotic mammals is largely extrapolated from data obtained from the cat and dog. However, valuable information may also be obtained from the lab animal literature wherein rodent species are used for cardiovascular research. Recommended dosages for cardiac and vascular drugs in small exotic mammals are summarized in Table 3.

Table 3. Therapeutics for use in small exotic mammals with cardiovascular disease.^6,31,36

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