Body mass and growth rates in captive chimpanzees (Pan troglodytes) cared for in African wildlife sanctuaries, zoological institutions, and research facilities.

Captive chimpanzees (Pan troglodytes) mature earlier in body mass and have a greater growth rate compared to wild individuals. However, relatively little is known about how growth parameters compare between chimpanzees living in different captive environments. To investigate, body mass was measured in 298 African sanctuary chimpanzees and was acquired from 1030 zoological and 442 research chimpanzees, using data repositories. An analysis of covariance, adjusting for age, was performed to assess same-sex body mass differences between adult sanctuary, zoological, and research populations. Piecewise linear regression was performed to estimate sex-specific growth rates and the age at maturation, which were compared between sexes and across populations using extra-sum-of-squares F tests. Adult body mass was greater in the zoological and resarch populations compared to the sanctuary chimpanzees, in both sexes. Male and female sanctuary chimpanzees were estimated to have a slower rate of growth compared with their zoological and research counterparts. Additionally, male sanctuary chimpanzees were estimated to have an older age at maturation for body mass compared with zoological and research males, whereas the age at maturation was similar across female populations. For both the zoological and research populations, the estimated growth rate was greater in males compared to females. Together, these data contribute to current understanding of growth and maturation in this species and suggest marked differences between the growth patterns of chimpanzees living in different captive environments.

Monitoring great ape heart health through innovative electrocardiogram technology: Training methodologies and welfare implications.

Assessing and treating cardiovascular disease (or heart disease) is a growing concern for institutions housing great apes, as it is a major cause of mortality in all four taxa managed in human care. As part of a proactive monitoring plan, zoological managers and veterinarians often elect to perform electrocardiograms (ECGs) on their great ape populations. ECGs noninvasively evaluate cardiac electrical activity, and are thereby capable of providing information regarding heart function. This electrical signature is transcribed as a visual display of waveforms, referred to as telemetry strips, and can detect irregularities in heart rhythm, also known as arrhythmia. While traditional 6- or 12-lead ECGs are recommended periodically as part of a thorough heart performance evaluation, here we discuss the KardiaMobile (KM) device as an additional primate welfare tool. KM is a small, Food and Drug Administration-cleared, clinical-grade mobile ECG monitor that requires only 30 s of pressure to flag heart rate or arrhythmic abnormalities. We detail the training process and applicability to great apes in human care.

GREAT APE HEART PROJECT GUIDELINES FOR THE ECHOCARDIOGRAPHIC ASSESSMENT OF GREAT APES.

Cardiovascular disease (CVD) has been identified as a major cause of mortality in all four great ape taxa in zoologic institutions. In an effort to better understand and treat CVD in captive great apes, a program called the Great Ape Heart Project (GAHP), based at Zoo Atlanta, collects and maintains a database of echocardiograms and other relevant medical information relating to the cardiac health status of great apes. Cardiac health assessments have become standard practice among North American zoos that house great apes and are recommended by all four great ape Species Survival Plans (SSP) for the assessment of CVD in captive great apes. As of December 31, 2017, more than 70 ape-holding institutions have submitted approximately 1,100 cardiac examinations of great apes to the GAHP, information from which is stored in the GAHP database. Transthoracic echocardiography is one of the most practical and cost-effective diagnostic imaging techniques for the evaluation of cardiac function in great apes. Standardization of echocardiographic measurements is critical for maximizing the diagnostic value of an echocardiographic exam and for utilization of stored information in comparative studies within and between the great ape taxa. The following manuscript offers suggestions for standardization of nomenclature, imaging technique, echocardiographic measurements, data storage, and reporting of cardiac exams for submission into the GAHP database with the goal of promoting consistency and quality in data collection.

Equine Cardiovascular Therapeutics.

Heart disease can be defined as any abnormality of the heart whether it is a cardiac dysrhythmia or structural heart disease, either congenital or acquired. Heart failure occurs when a cardiac abnormality results in the inability of the heart to pump enough blood to meet the body's needs. Heart disease can be present without leading to heart failure. Heart failure, however, is a consequence of heart disease. There are 4 main areas where the clinician can intervene to improve cardiac output with heart failure: preload, afterload, myocardial contractility, and heart rate.

Effects of acepromazine or methadone on midazolam-induced behavioral reactions in dogs.

This study evaluated whether acepromazine or methadone reduced behavioral parameters, overall excitement, and activity associated with midazolam administration to healthy dogs. Dogs received midazolam (M) alone [M: 0.25 mg/kg body weight (BW)] or with methadone (MM) (MM: 0.75 mg/kg BW) or acepromazine (MA) (MA: 0.03 mg/kg BW) or saline (S) solution alone, all intramuscularly. Two blinded observers evaluated behavioral parameters using video recordings 30 min before and after injection of drugs. Accelerometery was used to evaluate "total activity counts" (TAC) at baseline and post-treatment. Post-treatment excitement scores were significantly higher in M and MA compared to baseline, M and MM compared to S, and M compared to MA. Behavioral parameters showed significantly higher proportions of "pacing" post-treatment in all groups receiving midazolam, and "restlessness," "chewing/licking," and "sniffing" in M. No significant differences were found for TAC at baseline and post-treatment. Midazolam-induced paradoxical behavioral changes (excitation, panting, pacing, restlessness, licking/chewing, and vocalization) were not prevented by acepromazine or methadone in healthy dogs.

Effets de l'acépromazine ou de la méthadone sur les réactions comportementales induites par le midazolam chez les chiens. Cette étude a évalué si l'acépromazine ou la méthadone réduisait les paramètres comportementaux, le niveau d'excitation général et l'activité associée à l'administration de midazolam chez des chiens en santé. Les chiens ont reçu le midazolam (M) seul (M : 0,25 mg/kg poids corporel [PC]) ou avec de la méthadone (MM) (MM : 0,75 mg/kg PC) ou de l'acépromazine (MA) (MA : 0,03 mg/kg PC) ou une solution saline (S) seule, tous administrés par voie intramusculaire. Deux observateurs à l'aveugle ont évalué les paramètres comportementaux à l'aide d'enregistrements vidéo 30 minutes avant et après l'injection des médicaments. Un accéléromètre a été utilisé pour évaluer les «numérations de l'activité totale¼ (NAT) comme données de référence et après le traitement. Les notes d'excitation après le traitement étaient significativement supérieures pour M et MA comparativement aux données de référence, M et MM comparativement à S et M comparativement à MA. Les paramètres comportementaux ont montré des proportions significativement supérieures de «va-et-vient¼ après le traitement dans tous les groupes qui avaient reçu midazolam et une «agitation¼, de «mastication et léchage¼ et de «reniflement¼ dans M. Aucune différence significative n'a été constatée pour NAT aux données de référence et après le traitement. Les changements comportementaux paradoxes induits par le midazolam (excitation, halètement, va-et-vient, agitation, lèchage et mastication et vocalisation) n'ont pas été prévenus par l'acépromazine ni la méthadone chez les chiens en santé.(Traduit par Isabelle Vallières).

The effect of neonatal gene therapy with a gamma retroviral vector on cardiac valve disease in mucopolysaccharidosis VII dogs after a decade.

Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of the lysosomal enzyme ß-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs). This study determined the long-term effect of neonatal intravenous injection of a gamma retroviral vector (RV) on cardiac valve disease in MPS VII dogs. Transduced hepatocytes secreted GUSB into the blood for up to 11 years at levels similar to or greater than those achieved with enzyme replacement therapy (ERT). Valve regurgitation and thickening were scored from 0 (normal) to +4 (severely abnormal). At 1 year, untreated MPS VII dogs had mitral regurgitation, mitral valve thickening, aortic regurgitation, and aortic valve thickening scores of 2.3 ± 0.7, 2.3 ± 0.6, 1.8 ± 0.5, and 1.6 ± 0.7, respectively, which were higher than the values of 0.6 ± 0.1, 0.1 ± 0.4, 0.3 ± 0.8, and 0.1 ± 0.4, respectively, in treated MPS VII dogs. Treated MPS VII dogs maintained low aortic regurgitation and aortic valve thickening scores in their lifetime. Although mitral regurgitation and mitral valve thickening scores increased to 2.0 at ≥ 8 years of age in the treated MPS VII dogs, older normal dogs from the colony had similar scores, making it difficult to assess mitral valve disease. Older treated dogs had calcification within the mitral and the aortic valve annulus, while GUSB staining demonstrated enzyme activity within the mitral valve. We conclude that neonatal RV-mediated gene therapy reduced cardiac valve disease in MPS VII dogs for up to 11 years, and propose that neonatal initiation of ERT should have a similar effect.

Pathogenesis of mitral valve disease in mucopolysaccharidosis VII dogs.

Mucopolysaccharidosis VII (MPS VII) is due to the deficient activity of ß-glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs) in lysosomes and multisystemic disease with cardiovascular manifestations. The goal here was to determine the pathogenesis of mitral valve (MV) disease in MPS VII dogs. Untreated MPS VII dogs had a marked reduction in the histochemical signal for structurally-intact collagen in the MV at 6 months of age, when mitral regurgitation had developed. Electron microscopy demonstrated that collagen fibrils were of normal diameter, but failed to align into large parallel arrays. mRNA analysis demonstrated a modest reduction in the expression of genes that encode collagen or collagen-associated proteins such as the proteoglycan decorin which helps collagen fibrils assemble, and a marked increase for genes that encode proteases such as cathepsins. Indeed, enzyme activity for cathepsin B (CtsB) was 19-fold normal. MPS VII dogs that received neonatal intravenous injection of a gamma retroviral vector had an improved signal for structurally-intact collagen, and reduced CtsB activity relative to that seen in untreated MPS VII dogs. We conclude that MR in untreated MPS VII dogs was likely due to abnormalities in MV collagen structure. This could be due to upregulation of enzymes that degrade collagen or collagen-associated proteins, to the accumulation of GAGs that compete with proteoglycans such as decorin for binding to collagen, or to other causes. Further delineation of the etiology of abnormal collagen structure may lead to treatments that improve biomechanical properties of the MV and other tissues.

Neonatal gene therapy with a gamma retroviral vector in mucopolysaccharidosis VI cats.

Mucopolysaccharidosis (MPS) VI is due to a deficiency in the activity of N-acetylgalactosamine 4-sulfatase (4S), also known as arylsulfatase B. Previously, retroviral vector (RV)-mediated neonatal gene therapy reduced the clinical manifestations of MPS I and MPS VII in mice and dogs. However, sulfatases require post-translational modification by sulfatase-modifying factors. MPS VI cats were injected intravenously (i.v.) with a gamma RV-expressing feline 4S, resulting in 5 ± 3 copies of RV per 100 cells in liver. Liver and serum 4S activity were 1,450 ± 1,720 U/mg (26-fold normal) and 107 ± 60 U/ml (13-fold normal), respectively, and were directly proportional to the liver 4S protein levels for individual cats. This study suggests that sulfatase-modifying factor (SUMF) activity in liver was sufficient to result in active enzyme despite overexpression of 4S. RV-treated MPS VI cats achieved higher body weights and longer appendicular skeleton lengths, had reduced articular cartilage erosion, and reduced aortic valve thickening and aortic dilatation compared with untreated MPS VI cats, although cervical vertebral bone lengths were not improved. This demonstrates that therapeutic expression of a functional sulfatase protein can be achieved with neonatal gene therapy using a gamma RV, but some aspects of bone disease remain difficult to treat.

Long-term restoration of cardiac dystrophin expression in golden retriever muscular dystrophy following rAAV6-mediated exon skipping.

Although restoration of dystrophin expression via exon skipping in both cardiac and skeletal muscle has been successfully demonstrated in the mdx mouse, restoration of cardiac dystrophin expression in large animal models of Duchenne muscular dystrophy (DMD) has proven to be a challenge. In large animals, investigators have focused on using intravenous injection of antisense oligonucleotides (AO) to mediate exon skipping. In this study, we sought to optimize restoration of cardiac dystrophin expression in the golden retriever muscular dystrophy (GRMD) model using percutaneous transendocardial delivery of recombinant AAV6 (rAAV6) to deliver a modified U7 small nuclear RNA (snRNA) carrying antisense sequence to target the exon splicing enhancers of exons 6 and 8 and correct the disrupted reading frame. We demonstrate restoration of cardiac dystrophin expression at 13 months confirmed by reverse transcription-PCR (RT-PCR) and immunoblot as well as membrane localization by immunohistochemistry. This was accompanied by improved cardiac function as assessed by cardiac magnetic resonance imaging (MRI). Percutaneous transendocardial delivery of rAAV6 expressing a modified U7 exon skipping construct is a safe, effective method for restoration of dystrophin expression and improvement of cardiac function in the GRMD canine and may be easily translatable to human DMD patients.

The aorta in humans and African great apes, and cardiac output and metabolic levels in human evolution.

Humans have a larger energy budget than great apes, allowing the combination of the metabolically expensive traits that define our life history. This budget is ultimately related to the cardiac output, the product of the blood pumped from the ventricle and the number of heart beats per minute, a measure of the blood available for the whole organism physiological activity. To show the relationship between cardiac output and energy expenditure in hominid evolution, we study a surrogate measure of cardiac output, the aortic root diameter, in humans and great apes. When compared to gorillas and chimpanzees, humans present an increased body mass adjusted aortic root diameter. We also use data from the literature to show that over the human lifespan, cardiac output and total energy expenditure follow almost identical trajectories, with a marked increase during the period of brain growth, and a plateau during most of the adult life. The limited variation of adjusted cardiac output with sex, age and physical activity supports the compensation model of energy expenditure in humans. Finally, we present a first study of cardiac output in the skeleton through the study of the aortic impression in the vertebral bodies of the spine. It is absent in great apes, and present in humans and Neanderthals, large-brained hominins with an extended life cycle. An increased adjusted cardiac output, underlying higher total energy expenditure, would have been a key process in human evolution.

Long-term amelioration of feline Mucopolysaccharidosis VI after AAV-mediated liver gene transfer.

Mucopolysaccharidosis VI (MPS VI) is caused by deficient arylsulfatase B (ARSB) activity resulting in lysosomal storage of glycosaminoglycans (GAGs). MPS VI is characterized by dysostosis multiplex, organomegaly, corneal clouding, and heart valve thickening. Gene transfer to a factory organ like liver may provide a lifetime source of secreted ARSB. We show that intravascular administration of adeno-associated viral vectors (AAV) 2/8-TBG-felineARSB in MPS VI cats resulted in ARSB expression up to 1 year, the last time point of the study. In newborn cats, normal circulating ARSB activity was achieved following delivery of high vector doses (6 × 10(13) genome copies (gc)/kg) whereas delivery of AAV2/8 vector doses as low as 2 × 10(12) gc/kg resulted in higher than normal serum ARSB levels in juvenile MPS VI cats. In MPS VI cats showing high serum ARSB levels, independent of the age at treatment, we observed: (i) clearance of GAG storage, (ii) improvement of long bone length, (iii) reduction of heart valve thickness, and (iv) improvement in spontaneous mobility. Thus, AAV2/ 8-mediated liver gene transfer represents a promising therapeutic strategy for MPS VI patients.

Upregulation of elastase activity in aorta in mucopolysaccharidosis I and VII dogs may be due to increased cytokine expression.

Mucopolysaccharidosis I (MPS I) and MPS VII are due to loss-of-function mutations within the genes that encode the lysosomal enzymes alpha-l-iduronidase and beta-glucuronidase, respectively, and result in accumulation of glycosaminoglycans and multisystemic disease. Both disorders are associated with elastin fragmentation and dilatation of the aorta. Here, the pathogenesis and effect of gene therapy on aortic disease in canine models of MPS was evaluated. We found that cathepsin S is upregulated at the mRNA and enzyme activity level, while matrix metalloproteinase 12 (MMP-12) is upregulated at the mRNA level, in aortas from untreated MPS I and MPS VII dogs. Both of these proteases can degrade elastin. In addition, mRNA levels for the interleukin 6-like cytokine oncostatin M were increased in MPS I and MPS VII dog aortas, while mRNA for tumor necrosis factor alpha and toll-like receptor 4 were increased in MPS VII dog aortas. These cytokines could contribute to upregulation of the elastases. Neonatal intravenous injection of a retroviral vector expressing beta-glucuronidase to MPS VII dogs reduced RNA levels of cathepsin S and MMP-12 and aortic dilatation was delayed, albeit dilatation developed at late times after gene therapy. A post-mortem aorta from a patient with MPS VII also exhibited elastin fragmentation. We conclude that aortic dilatation in MPS I and MPS VII dogs is likely due to degradation of elastin by cathepsin S and/or MMP-12. Inhibitors of these enzymes or these cytokine-induced signal transduction pathways might reduce aortic disease in patients with MPS.

Activin IIB receptor blockade attenuates dystrophic pathology in a mouse model of Duchenne muscular dystrophy.

Modulation of transforming growth factor-ß (TGF-ß) signaling to promote muscle growth holds tremendous promise for the muscular dystrophies and other disorders involving the loss of functional muscle mass. Previous studies have focused on the TGF-ß family member myostatin and demonstrated that inhibition of myostatin leads to muscle growth in normal and dystrophic mice. We describe a unique method of systemic inhibition of activin IIB receptor signaling via adeno-associated virus (AAV)-mediated gene transfer of a soluble form of the extracellular domain of the activin IIB receptor to the liver. Treatment of mdx mice with activin IIB receptor blockade led to increased skeletal muscle mass, increased force production in the extensor digitorum longus (EDL), and reduced serum creatine kinase. No effect on heart mass or function was observed. Our results indicate that activin IIB receptor blockade represents a novel and effective therapeutic strategy for the muscular dystrophies.

Percutaneous Transendocardial Delivery of Self-complementary Adeno-associated Virus 6 Achieves Global Cardiac Gene Transfer in Canines.

Achieving efficient cardiac gene transfer in a large animal model has proven to be technically challenging. Previous strategies have used cardiopulmonary bypass or dual catheterization with the aid of vasodilators to deliver vectors, such as adenovirus, adeno-associated virus (AAV), or plasmid DNA. Although single-stranded AAV (ssAAV) vectors have shown the greatest promise, they suffer from delayed expression, which might be circumvented using self-complementary vectors. We sought to optimize cardiac gene transfer using a percutaneous transendocardial injection catheter to deliver adeno-associated viral vectors to the canine myocardium. Four vectors were evaluated-ssAAV9, self-complementary AAV9 (scAAV9), scAAV8, scAAV6-so that comparison could be made between single-stranded and self-complementary vectors as well as among serotypes 9, 8, and 6. We demonstrate that scAAV is superior to ssAAV and that AAV 6 is superior to the other serotypes evaluated. Biodistribution studies revealed that vector genome copies were 15-4,000 times more abundant in the heart than in any other organ for scAAV6. Percutaneous transendocardial injection of scAAV6 is a safe, effective method to achieve efficient cardiac gene transfer.

Percutaneous transendocardial delivery of self-complementary adeno-associated virus 6 achieves global cardiac gene transfer in canines.

Achieving efficient cardiac gene transfer in a large animal model has proven to be technically challenging. Previous strategies have used cardiopulmonary bypass or dual catheterization with the aid of vasodilators to deliver vectors, such as adenovirus, adeno-associated virus (AAV), or plasmid DNA. Although single-stranded AAV (ssAAV) vectors have shown the greatest promise, they suffer from delayed expression, which might be circumvented using self-complementary vectors. We sought to optimize cardiac gene transfer using a percutaneous transendocardial injection catheter to deliver adeno-associated viral vectors to the canine myocardium. Four vectors were evaluated--ssAAV9, self-complementary AAV9 (scAAV9), scAAV8, scAAV6--so that comparison could be made between single-stranded and self-complementary vectors as well as among serotypes 9, 8, and 6. We demonstrate that scAAV is superior to ssAAV and that AAV 6 is superior to the other serotypes evaluated. Biodistribution studies revealed that vector genome copies were 15-4,000 times more abundant in the heart than in any other organ for scAAV6. Percutaneous transendocardial injection of scAAV6 is a safe, effective method to achieve efficient cardiac gene transfer.

A novel locus for dilated cardiomyopathy maps to canine chromosome 8.

Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, often leads to heart failure and sudden death. While a substantial proportion of DCMs are inherited, mutations responsible for the majority of DCMs remain unidentified. A genome-wide linkage study was performed to identify the locus responsible for an autosomal recessive inherited form of juvenile DCM (JDCM) in Portuguese water dogs using 16 families segregating the disease. Results link the JDCM locus to canine chromosome 8 with two-point and multipoint lod scores of 10.8 and 14, respectively. The locus maps to a 3.9-Mb region, with complete syntenic homology to human chromosome 14, that contains no genes or loci known to be involved in the development of any type of cardiomyopathy. This discovery of a DCM locus with a previously unknown etiology will provide a new gene to examine in human DCM patients and a model for testing therapeutic approaches for heart failure.

Association of periodontal disease, oral procedures, and other clinical findings with bacterial endocarditis in dogs.

OBJECTIVE: To identify risk factors potentially associated with the development of bacterial endocarditis in dogs and determine whether periodontal disease and surgical procedures (oral and nonoral) were associated with bacterial endocarditis. DESIGN: Retrospective case-control study. ANIMALS: 76 dogs with (cases) and 80 dogs without (controls) bacterial endocarditis. PROCEDURES: Medical records were reviewed for information on signalment, physical examination findings, recent medical history, and results of echocardiography, clinicopathologic testing, and necropsy. RESULTS: None of the dogs with endocarditis had a history of undergoing any dental or oral procedure in the 3 months prior to the diagnosis of endocarditis, and no significant difference was found between groups with regard to the prevalence of oral infection. Dogs with endocarditis were significantly more likely to have undergone a nonoral surgical procedure that required general anesthesia in the preceding 3 months or to have developed a new heart murmur or a change in intensity of an existing heart murmur. Preexisting cardiac dis-ease (congenital or acquired) was not found to be a risk factor. CONCLUSIONS AND CLINICAL RELEVANCE: Results did not provide any evidence of an association between bacterial endocarditis in dogs and either dental or oral surgical procedures or oral infection. Findings suggested that the routine use of prophylactic antimicrobial administration in dogs undergoing oral procedures needs to be reevaluated.

Pharmacokinetics of furosemide after intravenous, oral and transdermal administration to cats.

OBJECTIVES: The aim of this study was to determine the pharmacokinetics of furosemide in cats following intravenous (IV), oral and transdermal administration. METHODS: This study used six healthy adult cats in a three-phase design to compare plasma furosemide concentrations in cats that received one IV 2 mg/kg dose of furosemide, one oral 2 mg/kg dose of furosemide and 3 days of q12h dosing with 2 mg/kg furosemide transdermally applied to the ear pinna. RESULTS: After IV administration the elimination half-life was (mean and coefficient of variation) 2.25 h (72%), systemic clearance was 149 ml/kg/h (27.4%) and volume of distribution was 227 ml/kg (22%). After oral administration the terminal half-life was 1.2 h (18.7%), peak concentration was 3.4 µg/ml (51.7%) and bioavailability was 48.4%. The transdermal plasma concentrations were undetectable or very low at most time points, and pharmacokinetics were not determined from the transdermal dose. CONCLUSIONS AND RELEVANCE: Furosemide was rapidly eliminated in cats after oral and IV administration and is probably best administered orally at least q12h in cats with heart failure. The oral dose absorbed was approximately 50%, but the absorption from transdermal administration was negligible.

Interstitial myocardial fibrosis in a captive chimpanzee (Pan troglodytes) population.

The clinical and necropsy records of 36 (25 male and 11 female) chimpanzees age 10 to 40 y old that died over a 6-y period (2001 to 2006) were reviewed. All animals had annual physical exams that included electrocardiograms and serial blood pressures. Nine of the 36 animals had a complete cardiac evaluation by a board certified veterinary cardiologist, and 7 of the 36 animals (19%) were diagnosed with some form of cardiomyopathy. Systemic hypertension was noted in 3 cases. Cardiac arrhythmias (ventricular ectopy) were seen in 15 (12 male and 3 female) of the 36 animals (42%). Sudden cardiac death (SCD) occurred in 13 (11 male and 2 female) chimps (36%) and was the leading cause of death (n = 13), followed by renal failure (n = 9) and septicemia (n = 3). Histologic examination of the hearts revealed interstitial myocardial fibrosis (IMF) in 29 chimpanzees (81%), and all of the animals that died suddenly due to cardiac causes had IMF to varying degrees. More data will be needed to identify the possible causes of IMF in captive chimpanzees, and IMF may be associated with arrhythmias and SCD in these animals.

Assessment of plasma cardiac troponin I concentration as a means to differentiate cardiac and noncardiac causes of dyspnea in cats.

OBJECTIVE: To determine whether plasma cardiac troponin I (cTnI) concentrations can be used to discriminate cardiac from noncardiac causes of dyspnea in cats. DESIGN: Prospective, multicenter study. ANIMALS: Client-owned cats with dyspnea attributable to congestive heart failure (D-CHF; n=31) or to noncardiac causes (D-NCC; n=12). PROCEDURES: For each cat, plasma cTnI concentration was analyzed by use of a solid-phase radial partition immunoassay; values in cats with D-CHF and D-NCC were compared. A receiver operating characteristic curve was analyzed to determine the accuracy of plasma cTnI concentration for diagnosis of D-CHF. RESULTS: Median plasma concentration of cTnI in cats with D-CHF (1.59 ng/mL; range, 0.20 to 30.24 ng/mL) was significantly higher than in cats with D-NCC (0.165 ng/mL; range, 0.01 to 1.42 ng/mL). With regard to the accuracy of plasma cTnI concentration for diagnosis of D-CHF, the area under the receiver operating characteristic curve was 0.84. At plasma concentrations > or = 0.2 ng/mL, cTnI had 100% sensitivity but only 58% specificity for identification of CHF as the cause of dyspnea. At plasma concentrations > or = 1.43 ng/mL, cTnI had 100% specificity and 58% sensitivity for identification of CHF as the cause of dyspnea. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of the derived diagnostic limits, CHF as the cause of dyspnea could be ruled in or ruled out without additional diagnostic testing in > 50% of the study cats. Measurement of plasma cTnI concentration may be clinically useful for differentiation of cardiac from noncardiac causes of dyspnea in cats. (J Am Vet