Acaptive adult sexually intact female Harris hawk (Parabuteo unicinctus) that was a permanent resident at the Wildlife Hospital of Louisiana (owing to a previous tibiotarsal fracture that rendered it un-releasable) was evaluated because of acute collapse. The hawk had been kept at the facility for 5 years. It was displayed for educational purposes > 12 times/y and had been considered healthy; general health examinations were performed twice yearly, and the bird had been vaccinated against West Nile virus annually with a killed vaccine. The hawk had reportedly collapsed (becoming recumbent and nonresponsive) for unknown reasons during an educational activity (in which it was being exhibited on the handler's fist) and was brought to the Zoological Medicine service at the Louisiana State University Veterinary Teaching Hospital for emergency care. At the time of examination, the hawk was quiet and recumbent but responsive to stimulus; it weighed 1.01 kg (2.22 lb), and its body condition score was assessed as ideal (3 on a scale of 1 [emaciated] to 5 [obese]).1 Results of a physical examination, including cardiorespiratory auscultation, were unremarkable. Initial supportive care included administration of a balanced crystalloid solutiona (40 mL/kg [18 mL/lb], SC, once) and transfer to a heated oxygen cage with an oxygen flow rate of 4 L/min. Approximately 30 minutes later, the patient's posture and demeanor were considered adequate. No clinically meaningful response to supplemental oxygen therapy was observed, and the treatment was discontinued. A blood sample was collected from the right jugular vein and submitted to the facility's diagnostic laboratory for a CBC and plasma biochemical analysis. Differential diagnoses included respiratory disease (such as aspergillosis), cardiovascular disease, metabolic disorder, neurologic disease, and toxicosis. Results of hematologic examination did not vary substantially from previous values for the same hawk. Radiographs were obtained under general anesthesia, and no clinically important findings were detected except for a healed malunion segmental fracture of the right tibiotarsus and moderate degenerative joint disease of the left tibiotarsal-tarsometarsal joint. Recovery from anesthesia was uneventful, and the hawk was hospitalized for further diagnostic evaluation.
The patient's general condition was substantially improved within 24 hours after admission, and the initial clinical signs resolved completely. Two days after initial examination, coelioscopy was performed under general anesthesia with a left lateral approach; results revealed mild hypervascularization and cloudiness of the air sac membranes at the junction of the caudal thoracic and abdominal air sacs. A focal brown to black discoloration measuring from 5 to 10 mm was observed in the caudal aspect of the left lung. Samples of the affected air sac and lung lesion were collected and submitted for histologic examination and fungal culture. The lung lesion was diagnosed histologically as anthracosis. Remaining results were unremarkable, and fungal culture resulted in no growth. The patient was kept under observation for 3 days, during which no abnormal behavior was detected, and then was discharged to its regular caretakers. No medication was prescribed, but the staff was advised not to include the hawk in educational presentations until instructed otherwise.
The hawk was housed in its regular cage for 1 month, after which time it was deemed healthy and its use in educational presentations resumed. During the first educational activity after the initial presentation, the patient collapsed again and was reassessed by the Zoological Medicine service. Supportive care procedures (SC fluid administration, warming, and oxygen support) were performed as before, and a physical examination, CBC, and plasma biochemical analysis were performed, again with no abnormalities noted. The hawk appeared to return to its normal condition within the next 12 hours. Electrocardiography and echocardiography were performed to assess cardiovascular function. Findings on initial TCE examination performed under general anesthesia with isoflurane by a midline approach were suggestive of dilated cardiac chambers, but proper echocardiographic views could not be obtained. Thus, TEE was performed under the same general anesthetic episode following a protocol previously described for use in birds.2 Both ventricles and both atria were subjectively considered dilated (Figure 1). Systolic dysfunction was detected on the basis of a low degree of fractional shortening (18%) of the left ventricle (because no reference range was available for Harris hawks, published data for healthy adult and juvenile red-tailed hawks [Buteo jamaicensis]3 were considered expected values; median fractional shortening of 50% [range, 7.9% to 90.6%] and 26.8% [range, 0% to 57.3%] have been described for the left and right ventricles, respectively). Bilateral atrioventricular insufficiency was diagnosed by use of color flow Doppler echocardiography. Mild to moderate coelomic effusion was detected, but centesis was not performed. Cardiomyopathy with right-and left-sided CHF was considered to be the most likely diagnosis. The patient recovered uneventfully from anesthesia and was hospitalized for further diagnostic tests and treatments.
Representative TEE image of a captive adult female Harris hawk (Parabuteo unicinctus) that was evaluated because of acute collapse. The left atrium and left ventricle appear severely dilated. LA = Left atrium. LV = Left ventricle.
Citation: Journal of the American Veterinary Medical Association 249, 2; 10.2460/javma.249.2.221
To assess major artery diameter, CT angiocardiography was performed 2 days later with the hawk under general anesthesia in accordance with a previously described protocol for birds.4 Helical CT images were acquired from the caudal cervical to caudal coelomic region with a 0.625-mm slice thickness and a standard algorithm. Additional postcontrast CT images were obtained with IV administration of an iodinated contrast mediumb (3.0 mL/kg [1.4 mL/lb] followed by an additional dose of 2.0 mL/kg [0.91 mL/lb]) injected at a rate of 1 mL/s via a catheter placed in the right ulnar vein. The second administration was needed because initial contrast administration did not provide adequate peak contrast agent concentration in the heart chambers and large vessels. Images were acquired immediately after injection; the left and right ventricles were subjectively considered severely enlarged, and biatrial enlargement was also detected (Figure 2). Postcontrast images revealed excellent contrast filling of the cranial vena cava, right atrium, right ventricle, pulmonary arteries, and, to a lesser extent, the pulmonary veins and left atrium. A rounded, focal, lateral marginal filling defect and luminal narrowing were present in the left main pulmonary artery, near the bifurcation of the main pulmonary arteries. Distal to the luminal filling defect, the pulmonary artery appeared mildly widened. The pulmonary veins were mildly tortuous and appeared dilated. There was poor filling of the aorta and both brachiocephalic trunks in the postcontrast images, compared with the precontrast images. Both trunks were subjectively narrowed, compared with other major arteries, with evidence of prestenotic dilation and poor contrast filling. Differential diagnoses that were considered included stricture, atherosclerosis, or hypertension. Stenosis of the left main pulmonary artery with a filling defect and tortuous right and left pulmonary veins were diagnosed. Biatrial and biventricular dilation with reduced cardiac output and poor filling of the brachiocephalic trunks were also diagnosed and considered attributable to decreased myocardial function. A high preload and high left atrial pressure were the likely causes of the tortuous pulmonary veins.
Representative transverse postcontrast CT angiography images of the heart of the same hawk as in Figure 1. Images were acquired in a helical scan between the caudal cervical region and the caudal aspect of the coelomic cavity with a 0.625-mm slice thickness and a standard algorithm. Postcontrast angiography was performed after IV administration of iodinated contrast medium (240 mg/mL; 3 mL/kg [1.4 mL/lb], followed by a second dose of 2 mL/kg [0.91 mL/lb]). A—The left and right atria appear severely enlarged. B—A focal, lateral, marginal rounded filling defect (cross) and luminal narrowing are present in the left main pulmonary artery, near the bifurcation of the main pulmonary arteries. C—The right pulmonary artery is focally stenotic (wide arrow); the right and left pulmonary veins are mildly tortuous and dilated (thin arrows). Ao = Aorta. L = Left. LA = Left atrium. MPA = Main pulmonary artery. PA = Pulmonary artery. RA = Right atrium. RV = Right ventricle.
Citation: Journal of the American Veterinary Medical Association 249, 2; 10.2460/javma.249.2.221
A provisional diagnosis of cardiomyopathy with right- and left-sided CHF was made. The hawk was removed from the educational program. Treatments included furosemidec (0.5 mg/kg [0.23 mg/lb], PO, q 24 h) to reduce volume overload and pimobendand (10 mg/kg [4.5 mg/lb], PO, q 12 h) for its inotropic and vasodilatory effects. Owing to the lack of information on pharmacokinetics of pimobendan in Harris hawks, the initial dosage was determined on the basis of results of a study5 investigating pharmacokinetics of a single dose of the drug in Hispaniolan Amazon parrots (Amazona ventralis). Ten days after pimobendan treatment was initiated, peak and trough plasma concentrations (3 and 12 hours, respectively, after morning dose) of the drug were measured in heparinized plasma by high-performance liquid chromatography as previously described5 (commercial testing was not available). The plasma drug concentrations were 25,196 ng/mL at the 3-hour time point and 715.97 ng/mL at the 12-hour time point. To our knowledge, therapeutic circulating concentrations of pimobendan in raptor species have not been reported; however, these values were extremely high, considering that the therapeutic concentration range in people has been reported to be between 5.2 and 7.9 ng/mL.6 The dosage of pimobendan was decreased to 0.25 mg/kg (0.11 mg/lb) orally every 12 hours. A CBC and plasma biochemical analysis were performed, with all values considered normal for this patient (with no clinically relevant changes from previous values), and no clinical signs of toxicosis were detected. Thirty days after the first measurement of plasma pimobendan concentrations, another blood sample was collected with the same protocol, and plasma was preserved at −80°C until submitted for testing at the same laboratory that was previously used to have plasma pimobendan concentration reassessed by the same methodology. However, owing to the experimental nature of the laboratory measurement, pimobendan analysis of the plasma sample was delayed for several months. Another blood sample was collected from the right jugular vein and tested for serum neutralizing antibodies against West Nile virus; results revealed an antibody titer of ≥ 320, which was considered to be a protective titer attributable to previous vaccination.
The hawk did not have any recurrence of clinical signs in the next 5 months, during which time pimobendan and furosemide treatments were continued as described. Recheck TEE examinations 1 and 3 months after the initial diagnosis did not reveal any increase in the cardiac chamber size or further loss of function, and coelomic effusion appeared to decrease over time. The hawk's behavior and demeanor remained subjectively normal, and no syncope-like episodes were observed.
Approximately 6 months after initial diagnosis, the hawk was found dead in its cage. At necropsy, performed within 6 hours after discovery of the cadaver, the 1.09-kg (2.4-lb) hawk was considered to be in good body condition with no substantial change in weight from the previous measurement. Moderate postmortem autolysis was present. A small amount of blood was noticed around both nares. The heart measured 40.68 × 27.76 mm at its base and 19.23 mm at the level of the ventricles (widest point in cross section), and weighed 16.7 g (1.5% of the body weight). The formula Mh = 0.014Mb0.91, where Mh corresponds to heart mass and Mb represents body mass,7 was used to calculate the expected appropriate heart mass for the patient (15.1 g). The actual heart weight represented a 10.6% increase over the expected heart weight. Thickness was 3.41 mm for the left ventricular wall, 4.57 mm for the interventricular septum, and 2.5 mm for the right ventricular wall. The great vessels extending from the heart were mildly to moderately enlarged. The lungs were diffusely dark red, with multifocal to coalescing, ill-defined black areas. On cut surface, the lungs oozed copious amounts of red fluid. There were two 5-mm-diameter red foci within the hepatic parenchyma, and multiple 2- to 3-cm-long thin white worms were present in the colon. The synovium of the right knee joint was diffusely brown to green, with numerous fine villous proliferations. The articular cartilage of the right femur was irregular with multifocal to coalescing areas of eburnation. The mid-diaphysis of the right tibiotarsus had evidence of chronic malunion of the fracture site. No other gross abnormalities were noted.
Histologic examination of the kidneys revealed moderate multifocal dilation of the tubules, which contained amorphous, homogeneous, eosinophilic to amphophilic material and spheroids. Distended tubules were lined by attenuated to degenerate or necrotic epithelium, characterized by shrunken cells, hypereosinophilic cytoplasm, nuclear pyknosis, and karyorrhexis. Within the lungs, the parabronchi were infiltrated multifocally by low numbers of heterophils. The parabronchial interstitium contained multifocal aggregates of macrophages with black granular pigment. Hepatic sections revealed periportal areas infiltrated by low to moderate numbers of lymphocytes with fewer plasma cells and heterophils, mild to moderate biliary hyperplasia, and bile ductules that were multifocally dilated and contained inspissated bile. There were scattered foci of lymphocytic and heterophilic inflammation throughout the liver. The thyroid gland was focally expanded by a follicular adenoma. The heart had rare degenerate cardiomyocytes, and there was mild thickening of the right atrioventricular valve. The epicardium was multifocally infiltrated by small numbers of lymphocytes and heterophils. The atrial septum was expanded by mild edema and infiltrated by low to moderate numbers of lymphocytes. There was infrequent degeneration of coronary and myocardial vessels, characterized by mild multifocal mural mineralization. The myocardium of the left atrium was infiltrated by low numbers of histiocytes and lymphocytes with rare heterophils, and mild interstitial fibrosis was present.
The clinical importance of the histopathologic changes observed in the hawk's heart remained undetermined. The cause for the renal tubular degeneration could not be definitively determined; however, this was suspected to be secondary to reduced renal blood flow. The remaining histologic findings were considered incidental and unlikely to have had any clinical relevance because the changes were considered mild. Bacterial culture of the lung isolated Escherichia coli and a Proteus sp; these were considered likely contaminants because of a lack of histopathologic changes consistent with bacterial pneumonia. Results of viral culture of heart, brain, and lymphoid tissue samples for West Nile virus were negative.
The whole-body radiographs that had been obtained 5 years earlier, when the hawk was admitted to the hospital for fracture assessment, were retrospectively compared with the most recent set of radiographic images; measurement of the heart relative to the thoracic cavity was determined in each set of radiographs. The width of the cardiac silhouette was 69% of the width of the thoracic cavity at the time of diagnostic evaluation of syncope, compared with 52% on the intake images.
Results of the tests for plasma pimobendan concentrations submitted after the dosage was adjusted were received after the necropsy was performed. The peak concentration of the drug (at 3 hours after morning dose) was 16.8 ng/mL; at 12 hours after morning dose, the concentration was below the lower limit of detection (1 ng/mL).
Discussion
In the Harris hawk of this report, although no clinically important microscopic changes within the heart were found at necropsy, the clinical findings, disease progression, and results of antemortem diagnostic tests were highly suggestive of severe cardiac dysfunction with right- and left-sided CHF. Congestive heart failure is a clinical syndrome characterized by progressive cardiac dysfunction that results in activation of the renin-angiotensin-aldosterone system and ultimately results in fluid accumulation. Briefly, we defined CHF as a clinical syndrome characterized by fluid and sodium retention caused by heart disease.8,9 The cause of death could not be definitely determined; however, the cardiac deficits reported herein are highly suggestive of severe cardiac dysfunction and most likely contributed to the bird's death. In our opinion, the most likely cause of sudden cardiac death in this patient was a cardiac arrhythmia, as has been reported in human patients.10
Cardiac diseases have been reported in avian species, with cardiovascular diseases being more common in captive birds because of restricted exercise and poor diets.11,12 Echocardiography allows noninvasive assessment of the cardiac function, structure, and hemodynamics3; a transcoelomic approach is commonly used and has been described for avian species.13,14 Conventional cardiological examination is complicated, and its use for assessment of cardiac function in birds, compared with domestic animals, is often unrewarding because of the anatomic and physiologic characteristics of avian species.11 The heart is located in an indentation of the keel and surrounded by air sacs; therefore, the available acoustic windows and cardiac views are limited. In the hawk of this report, TCE results were suggestive of cardiac changes but TEE was used for better assessment of the heart. The TEE method has been shown to provide better resolution images and details of cardiovascular structures and to allow more reliable measurements than those obtained by TCE in hawks.3 All TEE procedures were performed by 1 individual (CAR) to reduce variations in measurements and interpretation. The TEE results confirmed cardiomyopathy, contractile dysfunction, and bilateral valvular insufficiency.
Computed tomographic angiocardiography was performed to assess major arterial diameters, to allow a gross assessment of cardiovascular hemodynamics, and to screen for vascular stenosis resulting from atherosclerosis. Although a stenosis was identified in the pulmonary arteries, the presence of an atherosclerotic plaque could not be confirmed by this method, and no plaques were found on necropsy. However, this case illustrated the feasibility of this diagnostic test for use in birds and the utility of the information collected for cardiovascular assessment.
Pimobendan, 2-(4–methoxy-phenyl)–5-(5–methyl–3–oxo-4,5dihydro-2H–6-pyridazinyl)-benzimidazole, is a cardiotonic vasodilator with activity derived from a combination of phosphodiesterase III inhibition and calcium sensitization of myocardial contractile proteins.15,16 An investigation of the literature revealed 1 published clinical report17 that described use of pimobendan in an avian patient (an African grey parrot [Psittacus erithacus]). In that parrot, the drug was used in combination with other medications in addition to furosemide, and the pimobendan dosage used (0.25 mg/kg [0.11 mg/lb], PO, q 12 h) appeared low in view of the more recent pharmacokinetic data from Hispaniolan Amazon parrots.5,17 For the hawk of the present report, the initial pimobendan dose of 10 mg/kg was determined on the basis of the pharmacokinetic data from Hispaniolan Amazon parrots, in which the same dose yielded a maximum plasma concentration of 8.26 ng/mL 3 hours after administration of a suspension created from commercial tablets.5 However, 10 days after the treatment was initiated in our patient, peak and trough plasma drug concentrations detected were approximately 3,200 and 91 times the highest therapeutic concentration reported for human patients, respectively.6 As a result, the dose was reduced to 0.25 mg/kg, which is the recommended dose in dogs. Unfortunately, results for the second measurement of plasma pimobendan concentration were not available prior to the patient's death. At the lower dose, the drug did not appear to remain in the circulation at detectable concentrations 12 hours after the morning treatment, which suggested that more frequent drug administration may be necessary, although studies are needed to assess this hypothesis. The marked difference in plasma pimobendan concentrations in the Harris hawk of this report, compared with data reported for Hispaniolan Amazon parrots, suggested that the pharmacokinetics of the drug might vary between these species, possibly because of differences in oral bioavailability, although this is still unclear at this time. It could be hypothesized that in a carnivorous avian species, absorption of the medication may be more similar to that in carnivorous and omnivorous mammals than to that in herbivorous and omnivorous birds. Amazon parrots are also phylogenetically distant from Accipitriformes, and the extrapolation of pharmacokinetic data from psittacines to other avian species should be done with extreme caution. However, it must also be considered that the circulating pimobendan concentrations for 1 hawk may not be representative, and an individual patient anomaly or other factors (eg, technical error related to sample analysis) could have influenced these results. It is unclear whether the pimobendan treatment had any therapeutic benefit in our patient; although therapeutic concentrations of a drug in people may not correspond to those in avian species, in the absence of more complete information, we believe that decreasing the dose was the most reasonable decision for the welfare of this patient. Further studies are needed to assess adequate dosing for birds of prey as well as other species of birds. Interestingly, no toxic effect of the drug could be clinically detected in the hawk, even at the extremely high plasma concentrations identified. Pimobendan toxicosis resulting from overdose has been suggested to occur in dogs, and the cardiotoxic effects of high doses of the drug appear to be associated with exaggerated pharmacodynamic effects, as these could lead to arrhythmias owing to effects on calcium activity.18,19
Throughout the treatment, cardiac function in the hawk of this report remained apparently unchanged as assessed by recheck examinations. Recheck echocardiography revealed a subjective decrease in coelomic fluid accumulation over time, which was most likely attributable to the administration of furosemide and reduction in preload volume. Furosemide is a potent loop diuretic used for the treatment of hypertension and edematous states associated with cardiac, renal, and hepatic failure20 and is described as having a low therapeutic index in birds.21 Overdose can lead to excessive volume loss and activation of renin-angiotensin-aldosterone cascade; therefore, the lowest effective dose should be used.22 During the treatment period, no excessive urination was apparent, although the patient's water intake was notably increased. Water was made available at all times to prevent dehydration. Because the bird appeared to remain hydrated and the amount of coelomic fluid appeared to decrease with treatment, the furosemide dose was not changed.
The underlying etiopathogenesis of cardiac disease in this patient was not definitively identified and may have been multifactorial. Heart failure can be caused by abnormalities affecting the cardiac conduction system, valvular system, or myocardium; blood shunting; infection; impaired systolic and diastolic function; and inadequate preload or high afterload. We initially considered an infectious process leading to myocarditis as a possible cause. Myocarditis caused by West Nile virus has been reported in multiple species of birds and is particularly common in Accipitriformes.23,24 Myocardial cells are reported to be particularly targeted by the virus.24 In our patient, the measurement of West Nile virus titers by serum neutralization indicated high antibody titers, which could have been related to the vaccinations that had been given or to recent virus exposure. However, on necropsy, there were no inflammatory lesions suggestive of infection and viral culture results were negative. Therefore, West Nile virus was an unlikely cause of cardiac disease in this case. There was also no evidence of bacterial or fungal infection identified in this patient. However, it could not be ruled out that a previous infection caused the initial insult that led to myocardial damage, and if that occurred, the causative agent could not be determined. Valvular insufficiency has been reported as a cause of CHF25–29; in the hawk of the present report, bilateral valvular insufficiency was detected, but this was considered to be a likely consequence of cardiac dilation rather than the initial cause of the disease. The importance of the histopathologic changes identified in the patient at necropsy could not be determined. There was mild thickening of the right atrioventricular valve and a mild increase in interstitial fibrous connective tissue, compared with expected findings. These changes have previously been described in psittacines with heart failure,12 but the changes were mild in this patient and were considered incidental. Histopathologic changes associated with cardiomyopathy in raptors have not been well described, and severe clinical disease has previously been reported without microscopic changes within the heart,30 making the interpretation of the cardiac changes in this hawk difficult.
After the diagnosis of cardiomyopathy was determined, previous radiographs of the hawk were reviewed. The ratio of heart width to thoracic width on the first radiographs, obtained 5 years earlier, was approximately 50%, whereas on the last radiographs obtained, the ratio was approximately 70%. It is possible that the images were obtained at different phases of the cardiac cycle, respiration, or both, which could potentially have influenced the ratios. Heart-to-thoracic width ratios have been reported for psittacines,31,32 raptors (including Harris hawks), and waterfowl,33–35 and an influence of respiratory movements on such measurements has been reported in peregrine falcons (Falco peregrinus).34 However, although a difference was not detected at the time of radiographic evaluation following the initial collapse, this finding could have prompted an investigation for cardiac disease in this patient earlier.
Although cardiomyopathy has been reported in various avian species, including raptors, the investigation described here included the use of advanced diagnostic methodologies such as TEE and CT angiography that, to our knowledge, have not been reported for the clinical diagnosis of cardiac conditions in birds. Considering the lack of pharmacological information on cardiovascular treatments in birds, and the wide variability expected in pharmacokinetics and clinical effects of drugs in different species, therapeutic drug monitoring and regular cardiological follow-up examinations are recommended in the treatment and management of chronic cardiac disease in birds.
Acknowledgments
Support was provided by the Wildlife Hospital of Louisiana, School of Veterinary Medicine, Louisiana State University.
The authors declare that there were no conflicts of interest with respect to the research, authorship, or publication of this report.
Presented in abstract form at the International Conference on Avian, Herpetology and Exotic Mammal Medicine, Wiesbaden, Germany, April 2013; and the 34th Association of Avian Veterinarians Conference, Jacksonville, Fla, August 2013.
ABBREVIATIONS
| CHF | Congestive heart failure |
| TCE | Transcoelomic echocardiography |
| TEE | Transesophageal echocardiography |
Footnotes
Veterinary Plasmalyte A, Abbott Laboratories, North Chicago, Ill.
Iohexol 240 mg/mL, Omnipaque, GE Healthcare Inc, Princeton, NJ.
Furosemide Oral Solution, Roxane Laboratories Inc, Columbus, Ohio.
Vetmedin, Boehringer Ingelheim Vetmedica Inc, St Joseph, Mo.
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