Cardiovascular System

Greaves, Peter

doi:10.1016/b978-0-444-53856-7.00007-5

Cited by 9 publications

(19 citation statements)

References 331 publications

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“…Published reports describe this predominantly in the papillary muscle and the subendocardial areas (Ruben et al 2000;Greaves 2011), though it is also found in the left ventricle and septum (Jokinen et al 2011). This supports the hypothesis that this change could be the consequence of local vascular dysfunction, as these areas have a higher blood flow or oxygen requirement, and thus are most at risk for ischemia.…”

Section: Introductionsupporting

confidence: 72%

“…Because it is a typically progressive change, all these terms are accurate at some point in the development of the lesion (Jokinen et al 2011;Greaves 2011). This cardiomyopathy classically starts with focal necrosis of individual/isolated cardiomyocytes, followed by an inflammatory cell infiltration (may be mixed in nature in the early stage then mainly mononuclear).…”

Section: Discussionmentioning

confidence: 99%

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Spontaneous Cardiomyopathy in Young Sprague-Dawley Rats

et al. 2013

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Cardiovascular safety signals in nonclinical studies remain among the main reasons for drug attrition during pharmaceutical research and development. Drug-induced changes can be functional and/or associated with morphological alterations in the normal heart histology. It is therefore crucial to understand the normal variations in histology to discriminate test article-related changes from background lesions. Rodent progressive cardiomyopathy is probably the most commonly encountered change in control animals of nonclinical toxicity studies. A multisite study mimicking standard short-term toxicity studies using young male Sprague-Dawley rats was performed to better characterize this finding. Using an enhanced sectioning method for this research study, it was observed that the incidence of background cardiomyopathy was 100%. The vast majority of the microscopic findings were inflammatory in nature, with associated necrotic changes (defined as necrosis/inflammatory cell infiltrate) and these changes were mainly located in the myocardium of the mid region of the ventricles (the left side being predominantly affected). The monitored environmental factors in this study (multiple facilities, study duration, handling) did not have an effect on the incidence or severity of the spontaneous cardiomyopathy. In addition, cardiac-specific serum troponin levels were measured and were within the published control range.

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Section: Introductionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Spontaneous Cardiomyopathy in Young Sprague-Dawley Rats

et al. 2013

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“…The pathogenesis of cardiomyopathy in laboratory rats is suspected to be the result of focal ischemia from vascular function abnormalities, since lesions are associated with regions of the myocardium most sensitive to hypoxia. 11 The cause of cardiomyopathy in this population of wild rats remains undetermined.…”

Section: Discussionmentioning

confidence: 99%

“…Associations between right ventricular hypertrophy and cardiomyopathy are inconsistently described in the laboratory rat literature. 11,23 Studies of the physiology of wild Norway rats have found that heart weight was higher in males and females in the winter compared to the summer. 1,13 In one study, this increased heart weight was attributed to ventricular hypertrophy and was thought to be a physiologic adaptation to cold weather and/or the presence of renal pathology, although factors such as age and sexual maturity were not controlled for in the analysis.…”

Section: Discussionmentioning

confidence: 99%

“…24 The combination of myocarditis, myocardial fibrosis, and myocardial degeneration is characteristic of cardiomyopathy in laboratory rats, which are a domesticated strain of R. norvegicus. 7,11,15,23 Cardiomyopathy is a common spontaneous change that most often affects older males, although lesions can develop in rats as young as 3 months of age. 27 This is consistent with the results in this study population, in which the odds of cardiomyopathy increased with increasing weight (a proxy for age) 9 and male sex.…”

Section: Discussionmentioning

confidence: 99%

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Survey of Cardiovascular Pathology in Wild Urban Rattus norvegicus and Rattus rattus

et al. 2014

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Norway (Rattus norvegicus) and black rats (Rattus rattus) are common commensal pests, yet little is known about the ecology of wild rats, including their natural diseases. We describe microscopic cardiovascular pathology in a subset of a sample of 725 wild urban rats. Changes observed in the pulmonary blood vessels (n ¼ 199) included arteriolar medial hypertrophy (20.1%, n ¼ 40) and blood vessel mineralization (19.1%, n ¼ 38). Microscopic changes in the heart (n ¼ 200) included myocarditis (33.5%, n ¼ 67), fibrosis (6.0%, n ¼ 12), mineralization (9.5%, n ¼ 19), myocardial degeneration (22.0%, n ¼ 44), and right ventricular hypertrophy (4.5%, n ¼ 9). Rats with myocarditis, fibrosis, or myocardial degeneration were grouped into a composite variable: cardiomyopathy. Statistical analysis showed that the odds of being affected by cardiomyopathy were greater in male rats (odds ratio [OR] ¼ 2.49; 95% confidence interval [CI] ¼ 1.12-5.55) and heavier rats (OR ¼ 1.14; 95% CI ¼ 1.09-1.20). The odds of pulmonary arteriolar medial hypertrophy was greater in sexually mature rats (OR ¼ 2.35; 95% CI ¼ 0.75-7.36), while the odds of pulmonary vessel mineralization were greater in heavier rats (OR ¼ 1.07; 95% CI ¼ 1.03-1.11) and in black rats (OR ¼ 5.35; 95% CI ¼ 1.62-17.69) compared to Norway rats. To our knowledge, this is the first detailed description of pathology in the cardiovascular system of wild rats and demonstrates that cardiovascular disease is common. The impact of these lesions on individual and population health remains to be investigated. Keywords animals, cardiovascular diseases, disease, heart, pathology, pulmonary artery, rats, Rattus norvegicus, Rattus rattus, wild Norway and black rats (Rattus norvegicus and Rattus rattus) are among the most abundant and widespread mammalian species, inhabiting all continents except Antarctica.9 These rats are especially well adapted to living in close proximity to humans, making use of human harborage, refuse, and agricultural crops.9 This adaptation has resulted in a number of negative consequences for people, ranging from economic losses through food consumption to health risks associated with the transmission of zoonotic diseases.9,14 Despite humankind's long-standing association with Norway and black rats, there is still a number of significant gaps in our understanding of the ecology of these species. Perhaps the most notable gap is related to causes of natural morbidity and mortality.The life span of wild urban rats is short, with few individuals living beyond 1 year. 9 In contrast, the expected life span of laboratory rats ranges from 2 to 3 years. 22 The reason for this rapid population turnover in wild rats is unclear. Research has shown that predation does not significantly reduce population size.9 Similarly, long-term population effects of rat control activities, such as trapping and poisoning, are limited because of these rodents' high fecundity rates.9 Additionally, competition for food, habitat, and other resources has been suggested as a cause of rat m...

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