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Vertebral Heart Score in Rhesus Macaques (Macaca mulatta): Generating Normal Reference Intervals and Assessing its Validity for Identifying Cardiac Disease.

ABSTRACT: Vertebral heart scoring (VHS) is a semiquantitative method to assess the presence and severity of cardiomegaly by using thoracic radiographs. VHS in rhesus macaques (Macaca mulatta) has not been validated or used routinely in the clinical or research setting. We hypothesized that rhesus macaques with cardiac disease diagnosed by using echocardiography would have higher VHS than animals without cardiac disease. A total of 150 rhesus macaques were enrolled in this study. All animals underwent echocardiography and thoracic radiography (right lateral [RL], dorsoventral [DV], and ventrodorsal [VD] views).According to echocardiography, 121 rhesus macaques had no cardiac disease and were used to establish reference intervals for VHS. The remaining 29 macaques had hypertrophic cardiomyopathy (n = 20) or other cardiac disease (n = 9). Results showed that VHS of RL and VD views were significantly higher in macaques with any of the identified cardiac diseases and in the cardiac disease group that excluded hypertrophic cardiomyopathy. VHS of animals with HCM was not significantly different than that of control animals. In the RL view, VHS was moderately accurate for predicting the presence of cardiac disease, with an AUC of 0.71 and an optimal cut-off value of 10.25 (sensitivity: 62%, specificity: 77%). In the VD view, VHS was a mildly accurate test for cardiac disease, with an AUC of 0.654 and an optimal cut-off value of 10.65 (sensitivity, 66%;specificity, 63%). Study results indicated that VHS could be a useful screening tool for clinically identifying rhesus macaques with cardiac disease. However, VHS is unlikely to replace echocardiographic examination for determining the presence, type,and severity of cardiac disease in this species.

SUBMITTER: Williams AR

PROVIDER: S-EPMC7338866 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Echocardiography is commonly used for assessing cardiac structure and function in various species including non-human primates. A few previous studies reported normal echocardiographic reference intervals of clinically healthy rhesus macaques under sedation. However, these studies were under-powered, and the techniques were not standardized. In addition, body weight, age, and sex matched reference intervals should be established as echocardiographic measurements are commonly influenced by these variables. The purpose of this study was to establish reference intervals for complete echocardiographic parameters based on a large cohort of clinically healthy rhesus macaques with wide ranges of weight and age distributions using allometric scaling. RESULTS:A total of 823 rhesus macaques (ages 6?months to 31?years old; body weights 1.4 to 22.6?kg) were enrolled. Of these rhesus macaques, 421 were males and 402 were females. They were assessed with a complete echocardiographic examination including structural and functional evaluation under sedation with ketamine hydrochloride. The reference intervals of the key echocardiographic parameters were indexed to weight, age, and sex by calculating the coefficients of the allometric eq. Y?=?aMb. On correlation matrix, body weight, age, sex, and heart rate were significantly correlated with various echocardiographic parameters and some of the parameters were strongly correlated with body weight and age. Multiple regression analysis revealed that heart rate and body weight statistically significantly predicted several echocardiographic parameters. Valve regurgitation including tricuspid, aortic, pulmonic, and mitral regurgitations without other cardiac structural and functional abnormalities are common in clinically healthy rhesus macaques under ketamine sedation. CONCLUSIONS:In this study, the reference intervals of echocardiographic parameters were established by performing complete echocardiographic examinations on a large number of clinical healthy rhesus macaques. In addition, allometric scaling was performed based on their weight, and further indexed to age and sex. These allometrically scaled reference intervals can be used to accurately evaluate echocardiographic data in rhesus macaques and diagnose structural and functional evidence of cardiac disease.

Project description:Rhesus macaques are the most widely utilized nonhuman primate model in biomedical research. Previous efforts have validated fewer than 900 single nucleotide polymorphisms (SNPs) in this species, which limits opportunities for genetic studies related to health and disease. Extensive information about SNPs and other genetic variation in rhesus macaques would facilitate valuable genetic analyses, as well as provide markers for genome-wide linkage analysis and the genetic management of captive breeding colonies.We used the available rhesus macaque draft genome sequence, new sequence data from unrelated individuals and existing published sequence data to create a genome-wide SNP resource for Indian-origin rhesus monkeys. The original reference animal and two additional Indian-origin individuals were resequenced to low coverage using SOLiD™ sequencing. We then used three strategies to validate SNPs: comparison of potential SNPs found in the same individual using two different sequencing chemistries, and comparison of potential SNPs in different individuals identified with either the same or different sequencing chemistries. Our approach validated approximately 3 million SNPs distributed across the genome. Preliminary analysis of SNP annotations suggests that a substantial number of these macaque SNPs may have functional effects. More than 700 non-synonymous SNPs were scored by Polyphen-2 as either possibly or probably damaging to protein function and these variants now constitute potential models for studying functional genetic variation relevant to human physiology and disease.Resequencing of a small number of animals identified greater than 3 million SNPs. This provides a significant new information resource for rhesus macaques, an important research animal. The data also suggests that overall genetic variation is high in this species. We identified many potentially damaging non-synonymous coding SNPs, providing new opportunities to identify rhesus models for human disease.

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Vertebral Heart Score in Rhesus Macaques (Macaca mulatta): Generating Normal Reference Intervals and Assessing its Validity for Identifying Cardiac Disease.

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