Surgical placement of implantable cardiac loop recorders in great apes.

Cardiovascular disease is the leading cause of morbidity and mortality in zoologically managed adult great apes, accounting for 29%-77% of adult deaths in the North American population depending on the species. In an effort to better understand the underlying causes of heart disease, implantable loop recorders (ILRs) have been used in some cases to monitor great apes with suspected or known cases of arrhythmia. This is a 10-year review of the Great Ape Heart Project's experience of implanting 21 ILRs in 7 gorillas (Gorilla gorilla gorilla; 9 total ILR devices), 5 chimpanzees (Pan troglodytes, 11 total ILR devices), and 1 orangutan (Pongo abelii, 1 ILR device) in an effort to develop effective methods for surgical implantation and remote collection of the data for analysis.

Blood pressure monitoring in zoologically managed bonobos (Pan paniscus).

In response to the growing evidence that hypertension may play a significant role in the development of cardiovascular disease (CVD) in bonobos, the Great Ape Heart Project established a finger blood pressure (BP) monitoring protocol for zoo-housed bonobos. The ability to monitor BP without the use of anesthesia provides more opportunities to detect potential hypertension in its early stages allowing for therapeutic intervention that may slow the progression of CVD. No BP reference ranges exist for bonobos due to the lack of an established protocol, the difficulty of measuring BP in animals, and small sample size of zoo-housed bonobos. By working with all 8 institutions in North America that care for bonobos, it was possible to (1) investigate the feasibility of using finger BP devices, and (2) establish BP trends for male and female bonobos. Data were collected from May 2016 to March 2019. Zoos were asked to train for and collect BP measurements from any bonobos willing to participate, regardless of age, sex, or health status as well as to report on the quality of the training and measurements obtained. At the start of the study, the North American bonobo population consisted of 74 bonobos ages 5 years and older at 8 institutions. All 8 institutions submitted at total of 3656 BP readings from 50 bonobos (n = 23 females, n = 27 males; ages 5-51 years) representing 67.57% of the trainable population ages 5 years and older. Of the readings submitted, 2845 were determined to be good quality, reliable BP readings (77.81% useful BP measurements) for 36 of the 50 adult bonobos submitted for this study (59.01% of the adult population ages 10-51 years) but showed limitations in the protocol for the younger population. BP trend analysis showed significant differences between bonobos that were not on medication versus those treated with cardiac medications, with those on cardiac mediations having significantly higher systolic arterial pressure, diastolic arterial pressure, and mean arterial pressure (p ≤ 0.001 for all comparisons). Systolic BP generally increased over age classes (10-19, 20-29, 30-39, 40+ years).

MANAGEMENT OF ATRIAL FIBRILLATION, VENTRICULAR ARRHYTHMIA, LEFT VENTRICULAR DYSFUNCTION, AND SUBSEQUENT CARDIOPATHOLOGIC EVALUATION IN AN ORANGUTAN (PONGO PYGMAEUS × ABELII).

A 37-yr-old male vasectomized hybrid orangutan (Pongo pygmaeus × abelii) was diagnosed with left ventricular dysfunction during a preventative health care examination. Treatment was initiated with carvedilol. The following year, this orangutan was evaluated for intermittent lethargy. Following observation of an irregular cardiac rhythm during an echocardiogram, a lead II electrocardiogram revealed atrial fibrillation and ventricular arrhythmia. Additional treatment included amiodarone, furosemide, spironolactone, clopidogrel, and aspirin. An improved activity level was noted, and follow-up testing showed restoration of a sinus rhythm, reduced frequency of ventricular arrhythmia, and improved left ventricular function. The orangutan died 27 mon after initial diagnosis of heart disease, and a complete necropsy was performed. This article describes successful diagnosis and management of structural and arrhythmic heart disease in an orangutan, emphasizing the role of cardiac disease screening and behavioral training in apes, as well as the value of matching thorough antemortem and postmortem cardiac evaluation.

The glycocalyx: a central regulator of vascular function.

The endothelial glycocalyx is a specialized extracellular matrix that covers the apical side of vascular endothelial cells, projecting into the lumen of blood vessels. The composition of the glycocalyx has been studied in great detail, and it is known to be composed of a mixture of proteoglycans, glycosaminoglycans, and glycoproteins. Although this structure was once believed to be a passive physical barrier, it is now recognized as a multifunctional and dynamic structure that participates in many vascular processes, including but not limited to vascular permeability, inflammation, thrombosis, mechanotransduction, and cytokine signaling. Because of its participation in many physiological and pathophysiological states, comprehensive knowledge of the glycocalyx will aid future vascular biologists in their research. With that in mind, this review discusses the biochemical structure of the glycocalyx and its function in many vascular physiological processes. We also briefly review a more recent discovery in glycocalyx biology, the placental glycocalyx.

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.

NEOPLASIA IN SNAKES AT ZOO ATLANTA DURING 1992-2012.

A retrospective study was conducted to review neoplasia of captive snakes in the Zoo Atlanta collection from 1992 to 2012. Of 255 snakes that underwent necropsy and histopathologic examination at Zoo Atlanta during the study period, 37 were observed with neoplasia at necropsy. In those 37 snakes, 42 neoplastic lesions of 18 primary cell types were diagnosed. Thirty-five of those neoplasms (83.3%) were malignant, and of those, 19 were of mesenchymal origin, whereas 14 were of epithelial origin. The median annual rate of neoplasia at necropsy was 12.5% (interquartile range = 2.8-19.5%) over the 21-yr study period. The mean estimated age at death for snakes with neoplasia was 13.2 yr (range, 1-24 yr). Investigating the incidence and clinical significance of neoplasia in captive snakes is vital for developing effective preventative and treatment regimes.

ASSESSMENT OF SERUM 25-HYDROXYVITAMIN D CONCENTRATIONS IN TWO COLLECTIONS OF CAPTIVE GORILLAS (GORILLA GORILLA GORILLA).

Serum 25-hydroxyvitamin D concentrations were assessed in subadult to adult captive lowland gorillas ( Gorilla gorilla gorilla) (n = 26) at two institutions with different husbandry and management practices. Serum 25-hydroxyvitamin D (25[OH]D) concentrations for gorillas managed predominantly indoors was low (14.2 ± 5.9 ng/ml), despite consuming commercial biscuits fortified with vitamin D3. Concentrations of 25(OH)D in gorillas with near daily outdoor access were significantly higher than gorillas managed indoors, although many individuals still had serum values below concentrations recommended for adult humans. Consideration should be given to assessing 25(OH)D concentrations in all captive gorillas and providing specific supplementation, particularly to juveniles without access to direct sunlight.

Clinical canine parvovirus type 2C infection in a group of Asian small-clawed otters (Aonyx cinerea).

Despite the occurrence of clinical disease in a wide range of carnivore hosts, only vague accounts of clinical canine parvovirus type 2 (CPV-2) in any otter species have been reported in the literature. Over the course of 25 days, nine Asian small-clawed otters (Aonyx cinerea) presented for evaluation of inappetence, lethargy, vomiting, and diarrhea. A diagnosis of canine parvovirus type 2c was made based on electron microscopy, polymerase chain reaction, and DNA sequencing of group fecal samples. Supportive care was provided based on individual clinical assessment and included subcutaneous crystalline fluid therapy, antiemetics, antibiotics, appetite stimulants, and a neuraminidase inhibitor. Five of the nine otters exhibited moderate to severe disease requiring treatment, and one case was fatal despite supportive efforts. In light of this case report, CPV-2 should be recognized as a potential cause of gastrointestinal disease in Asian small-clawed otters.

Adipocyte endothelin B receptor activation inhibits adiponectin production and causes insulin resistance in obese mice.

AIMS: Endothelin-1 (ET-1) is elevated in patients with obesity and adipose tissue of obese mice fed high-fat diet (HFD); however, its contribution to the pathophysiology of obesity is not fully understood. Genetic loss of endothelin type B receptors (ETB) improves insulin sensitivity in rats and leads to increased circulating adiponectin, suggesting that ETB activation on adipocytes may contribute to obesity pathophysiology. We hypothesized that elevated ET-1 in obesity promotes insulin resistance by reducing the secretion of insulin sensitizing adipokines, via ETB receptor. METHODS: Male adipocyte-specific ETB receptor knockout (adETBKO), overexpression (adETBOX), or control littermates were fed either normal diet (NMD) or high-fat diet (HFD) for 8 weeks. RESULTS: RNA-sequencing of epididymal adipose (eWAT) indicated differential expression of over 5500 genes (p < 0.05) in HFD compared to NMD controls, and changes in 1077 of these genes were attenuated in HFD adETBKO mice. KEGG analysis indicated significant increase in metabolic signaling pathway. HFD adETBKO mice had significantly improved glucose and insulin tolerance compared to HFD control. In addition, adETBKO attenuated changes in plasma adiponectin, insulin, and leptin that is observed in HFD versus NMD control mice. Treatment of primary adipocytes with ET-1 caused a reduction in adiponectin production that was attenuated in cells pretreated with an ETB antagonist. CONCLUSION: These data indicate elevated ET-1 in adipose tissue of mice fed HFD inhibits adiponectin production and causes insulin resistance through activation of the ETB receptor on adipocytes.

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.

Echocardiographic parameters of captive western lowland gorillas (Gorilla gorilla gorilla).

A total of 163 echocardiographic studies on western lowland gorillas (Gorilla gorilla gorilla) were submitted for evaluation; 140 from 99 animals were suitable for analysis. Of these, 81 studies (42 studies from 35 males ranging in age from 11-41+ yr and 39 studies from 31 females ranging in age from 11-41+ yr) are reported here. Three studies from 3 females and 56 studies from 30 males were excluded from this report due to cardiac abnormalities. Cardiac parameters measured were aortic root (Ao Rt) diameter and left atrial (L atrium) size. Left ventricular (LV) measurements included left ventricular internal diameter in systole (LVID(s)) and diastole (LVID(d)) as well as diastolic septal (IVS) and posterior wall thickness (LVPW). Values considered to be normal in females > 11 yr of age were: Ao Rt < 3.5 cm, L atrium < 4.0 cm, LVID(d) < 5.0 cm, IVS < 1.4 cm, LVPW < 1.4 cm, and ejection fraction (EF) > 60%. The data from male gorillas show a separation in animals based on three cardiac parameters: systolic function, LV cavity size, and LV wall thickness. Male gorillas > 11 yr of age fall into two groups; unaffected and affected. Unaffected animals are defined as those with no echocardiographic abnormalities and a consistent Ao Rt of < 4.0 cm, LVID(d) of < 6.0 cm, IVS and LVPW of <1.5 cm, and an EF of > 58%. The affected group consisted of male gorillas that exhibited changes in echocardiographic parameters representing the presence of cardiovascular disease. The results determined in this database, gathered from data collected from 1999-2009, suggest a sex-based difference between males and females with predominantly males demonstrating evidence of cardiac disease. The most striking finding seen in this study is that of progressive LV hypertrophy and depressed LV EF in affected adult male gorillas.

Proliferative endometrial lesions in a group of Seba's short-tailed bats (Carollia perspicillata).

An unusually high prevalence of uterine changes was observed on necropsy in a group of 169 female Seba's short-tailed bats (Carollia perspicillata). In this case study, 27 animals were affected from 1997 to 2007, representing 16% of the group population. All bats were of an indeterminate age and originated from the same facility, but were housed in three different zoological institutions. Deaths occurred year round. Most animals were found dead, with no previous clinical signs. Clinical signs, when present, included a markedly distended abdomen, extended periods of time perched on the exhibit floor, lethargy, and anorexia. Histologic changes included florid segmental to diffuse endometrial hyperplasia and occasional hemorrhage and adenomyosis. The cause for this condition has not been determined.

Cardiac disease is linked to adiposity in male gorillas (Gorilla gorilla gorilla).

Cardiac disease is a major cause of morbidity and mortality for adult gorillas. Previous research indicates a sex-based difference with predominantly males demonstrating evidence of left ventricular hypertrophy. To evaluate these findings, we analyzed serum markers with cardiac measures in a large sample of gorillas. The study sample included 44 male and 25 female gorillas housed at American Association of Zoo and Aquariums (AZA)-accredited zoos. Serum samples were collected from fasted gorillas during routine veterinary health exams and analyzed to measure leptin, adiponectin, IGF-1, insulin, ferritin, glucose, triglycerides, and cholesterol. Cardiac ultrasonography via transthoracic echocardiogram was performed simultaneously. Three echocardiographic parameters were chosen to assess cardiac disease according to parameters established for captive lowland gorillas: left ventricular internal diameter, inter-ventricular septum thickness, and left ventricular posterior wall thickness. Our data revealed that high leptin, low adiponectin, and lowered cholesterol were significantly and positively correlated with measures of heart thickness and age in males but not in females. Lowered cholesterol in this population would be categorized as elevated in humans. High leptin and low adiponectin are indicative of increased adiposity and suggests a potential parallel with human obesity and cardiovascular disease in males. Interestingly, while females exhibited increased adiposity with age, they did not progress to cardiac disease.

Diagnosing cardiovascular disease in western lowland gorillas (Gorilla gorilla gorilla) with brain natriuretic peptide.

Cardiovascular disease is a leading cause of death in zoo-housed great apes, accounting for 41% of adult gorilla death in North American zoological institutions. Obtaining a timely and accurate diagnosis of cardiovascular disease in gorillas is challenging, relying on echocardiography which generally requires anesthetic medications that may confound findings and can cause severe side effects in cardiovascularly compromised animals. The measurement of brain natriuretic peptide (BNP) has emerged as a modality of interest in the diagnosis, prognosis and treatment of human patients with heart failure. This study evaluated records for 116 zoo-housed gorillas to determine relationships of BNP with cardiovascular disease. Elevations of BNP levels correlated with the presence of visible echocardiographic abnormalities, as well as reported clinical signs in affected gorillas. Levels of BNP greater 150 pb/mL should alert the clinician to the presence of myocardial strain and volume overload, warranting medical evaluation and intervention.

Passive transfer of maternal antibodies to West Nile virus in flamingo chicks (Phoenicopterus chilensis and Phoenicopterus ruber ruber).

Passive transfer of maternal antibodies against West Nile virus (WNV) was studied in a captive population of Chilean (Phoenicopterus chilensis) and Caribbean flamingos (Phoenicopterus ruber ruber). Transfer of WNV antibodies from hens to chicks was documented and measured by plaque-reduction neutralization test. Hen titers were significantly correlated to chick titers. Mean half-life of maternal WNV antibodies was 13.4 days in chicks for which half-life was measurable.

Implications of simian retroviruses for captive primate population management and the occupational safety of primate handlers.

Nonhuman primates can be naturally infected with a plethora of viruses with zoonotic potential, including retroviruses. These simian viruses present risks to both captive nonhuman primate populations and persons exposed to nonhuman primates. Simian retroviruses, including simian immunodeficiency virus, simian type D retrovirus, simian T-lymphotropic virus, and gibbon ape leukemia virus, have been shown to cause clinical disease in nonhuman primates. In contrast, simian foamy virus, a retrovirus that is highly prevalent in most nonhuman primates, has not been associated with clinical disease in naturally infected primates. Although it has been shown that human retrovirus infections with human T-lymphotropic virus and human immunodeficiency virus originated through multiple independent introductions of simian retroviruses into human populations that then spread globally, little is known about the frequency of such zoonotic events. In this article, exogenous simian retroviruses are reviewed as a concern for zoo and wildlife veterinarians, primate handlers, other persons in direct contact with nonhuman primates, and other nonhuman primates in a collection. The health implications for individual animals as well as managed populations in zoos and research institutions are discussed, the cross-species transmission and zoonotic disease potential of simian retroviruses are described, and suggestions for working safely with nonhuman primates are provided.

Uterine leiomyomas in three captive eastern Bongo (Tragelaphus eurycerus isaaci).

Uterine leiomyomas occurred in three eastern bongo (Tragelaphus eurycerus isaaci) 10, 15, and 16 yr of age at three separate zoological institutions. Two animals were nulliparous, and one had given birth to 14 calves over its lifetime. Two of the leiomyomas originated in the cervix. The third originated in the uterine wall and incorporated the body of the uterus and both uterine horns. The tumors in the two animals that had never calved were large and nonresectable. They were associated with gastrointestinal clinical signs including diarrhea, anorexia, and the inability to defecate. The tumor in the animal that had calved was an incidental finding at necropsy. Uterine leiomyomas have not been previously documented in the literature on eastern bongo.

Direct DNA hybridization at disposable graphite electrodes modified with carbon nanotubes.

The performance of glassy carbon (GCE) and graphite pencil electrodes (PGE) modified with multiwalled carbon nanotubes (CNTs) are compared, based on the direct electrochemical detection of nucleic acids. This is accomplished by monitoring the differential pulse voltammetry changes of the guanine signal. CNT-modified PGE compares favorably to that of the commonly used CNT-modified GCE owing to the intrinsic improved performance of the supporting PGE. The better intrinsic characteristics of the PGE are related to its composite structure and higher level of porosity compared to GCE. The performance characteristics of the direct DNA hybridization on the disposable CNT-modified PGE are studied in terms of optimum analytical conditions such as probe concentration, target concentration, hybridization time, and selectivity. The new DNA biosensor described here has shown some important advantages such being inexpensive, sensitive, selective, and able to generate reproducible results using a simple and direct electrochemical protocol.

Molecular characterization of a novel simian immunodeficiency virus lineage (SIVtal) from northern talapoins (Miopithecus ogouensis).

Simian immunodeficiency viruses (SIVs) are found in an extensive number of African primates, and humans continue to be exposed to these viruses by hunting and handling of primate bushmeat and following occupational exposures to captive nonhuman primates. Here, we report the molecular characterization of a new SIV lineage, SIVtal, from wild-caught and captive talapoin monkeys (Miopithecus ogouensis) from Cameroon and U.S. zoos, respectively. Phylogenetic tree analyses of a small fragment in the pol gene indicated that all SIVtal strains clustered together forming a single species-specific lineage. Full-length sequence analysis for two strains, SIVtal-00CM266 and SIVtal-01CM8023, from wild-caught animals in Cameroon confirmed that SIVtal was distinct from all primate lentiviruses isolated so far and represents a new SIV lineage. Phylogenetic analyses in different viral genes showed a significant clustering of the SIVtal lineage with the Cercopithecus-specific SIVs. In addition, SIVtal and Cercopithecus-specific SIVs share functional motifs in Gag and Env that distinguish them from other primate lentiviruses. Like SIVsyk and SIVdeb, a vpu gene homologue was also absent in SIVtal. Although northern talapoins belong to the Miopithecus genus, their SIVs belong to the Cercopithecus SIV lineage, suggesting evolution from a common ancestor or cross-species transmission between both primate genera.