Left ventricular function of the isolated, genetically obese rat's heart

Paradise, NF; Pilati, C F; Payne, Warren; Finkelstein, JA

doi:10.1152/ajpheart.1985.248.4.h438

Cited by 20 publications

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“…8,18 However, noninvasive methods such as echocardiography are limited in the extent to which mechanisms underlying these abnormalities can be identified. Animal models of obesity also have yielded little concrete information on the potential role of obesity in altering diastolic compliance, because of either contradictory results 19,20 or use of an animal model with many characteristics that are clearly different from human obesity. 19 -21 The rabbit model has been shown to be useful in the study of obesity-related hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Diastolic Compliance Is Reduced in Obese Rabbits

et al. 1999

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Abstract-Obesity often leads to symptoms of cardiopulmonary congestion associated with normal systolic but abnormal diastolic function. This study analyzed alterations in passive diastolic compliance in obesity using the rabbit model. New Zealand White rabbits were fed a normal (nϭ8) or 10% added fat diet (nϭ8 Key Words: heart Ⅲ stroke volume Ⅲ obesity Ⅲ computer modeling Ⅲ diastolic pressure-volume relationship O besity is independently associated with an increase in morbidity and mortality, resulting primarily from increased incidence of cardiovascular diseases such as stroke, coronary artery disease, and congestive heart failure. 1 The precise mechanisms leading to greater risk for developing congestive heart failure in obesity are unknown but may stem from the increased work load on the heart imposed by the combination of increased cardiac output, increased intravascular volume, hypertension, and cardiac hypertrophy. 2 Interestingly, some obese patients with symptoms of systemic and pulmonary congestion present with normal systolic function; however, diastolic function is often abnormal. 3 In fact, it has been estimated that 35% to 40% of patients with congestive heart failure present with diastolic dysfunction only. 4 Diastolic dysfunction may be simply described as a condition in which diastolic filling is impeded. However, diastolic filling of the left ventricle is a complex process determined by the interaction of several factors, including active ventricular relaxation and passive properties influencing left ventricular compliance. Active relaxation is related to calcium reuptake by the sarcoplasmic reticulum, whereas passive ventricular filling properties are determined by ventricular wall thickness, the dimensions of the ventricular cavities, and the structural properties of the cardiac tissue itself. A few studies have attempted to examine the diastolic pressurevolume relationship, 5,6 and the data suggested that morbidly obese patients exhibit abnormalities in diastolic filling, with or without the presence of hypertension or cardiac hypertrophy. 7,8 Although there is evidence that diastolic filling is altered in obesity, 7 it is difficult to determine from clinical studies what role altered diastolic compliance plays in diastolic dysfunction. Little is known about the mechanisms underlying abnormal diastolic function in obesity or the relative contributions of decrements in active versus passive relaxation to filling abnormalities. In addition, little is known about how quickly diastolic dysfunction becomes manifest during the development of obesity. Therefore, our purpose was to examine the passive end-diastolic pressure-volume relationship in isolated hearts of obese and control rabbits to determine the presence and extent of obesity-related decrements in passive diastolic compliance. In addition, we used computer models of circulatory function to predict systemic effects resulting from reduced compliance both at rest and during exercise.

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Section: Discussionmentioning

confidence: 99%

Diastolic Compliance Is Reduced in Obese Rabbits

et al. 1999

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“…Paradise et al, 7 studying the same model at 11 to 13 months, found diminished values of unnormalized wall stress, suggesting either reduced intrinsic contractility or dilation, whereas LV chamber compliance was not different from that of controls. LV hypertrophy was suggested by an increased ratio of LV mass to tibial length.…”

Section: Previous Studies In Animal Models Of Obesitymentioning

confidence: 93%

“…Nevertheless, such studies are limited. [5][6][7][8] Furthermore, most rodent models of obesity display features that are atypical of human disease, such as reduced fertility, altered linear growth, elevated levels of corticosteroids, and reduced lean body mass. These peculiarities limit their relevance for studies of cardiovascular pathophysiology.…”

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confidence: 99%

Cardiovascular Abnormalities in Transgenic Mice With Reduced Brown Fat

et al. 1999

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Background-A new model of murine obesity has recently been developed through transgenic ablation of brown adipose tissue that manifests typical metabolic complications of obesity, including insulin resistance and non-insulin-dependent diabetes mellitus. The cardiovascular phenotype has not been defined. Methods and Results-Transthoracic echocardiography, aortic catheterization, isolated whole-heart studies, and morphometric histology defined cardiac structure and function in 30 transgenic mice with reduced brown fat and 30 matched wild-type controls. Obesity was indicated by a 77% increase in body weight and was accompanied by elevated systemic pressures (mean aortic blood pressure 85Ϯ1 versus 66Ϯ2 mm Hg; PϽ0.01), left ventricular dilation and hypertrophy (mass/body weight 4.0Ϯ0.2 versus 2.7Ϯ0.3 mg/g; PϽ0.01), and high cardiac output (cardiac index 3.2Ϯ0.4 versus 2.4Ϯ0.1 mL ⅐ kg Ϫ1 ⅐ min

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“…Each of the F 2 (SHR ϫ BN) rats in our population was phenotyped for BWadj-HW, which shows a strong correlation with blood pressure in rat models (43,55), including segregating populations of rats (reviewed in Ref. 47).…”

Section: Discussionmentioning

confidence: 99%

Linkage analysis of neointimal hyperplasia and vascular wall transformation after balloon angioplasty

Nestor

Cicila

Karol

et al. 2006

Physiological Genomics

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age analysis of neointimal hyperplasia and vascular wall transformation after balloon angioplasty. Physiol Genomics 25: 286 -293, 2006. First published January 24, 2006 doi: 10.1152/physiolgenomics.00135.2005.-Neointimal hyperplasia (NIH), a result of vascular injury, is due to the migration and proliferation of smooth muscle cells through the media and internal elastic lamina leading to vascular occlusion. We used a rat model to find the genetic regions controlling NIH after endothelial denudation in two divergent inbred strains of rats. The Brown Norway (BN) and spontaneously hypertensive rat (SHR) strains have a 2.5-fold difference in injury-induced NIH. A population of 301 F2 (SHR ϫ BN) rats underwent a standard vascular injury followed by phenotyping 8 wk after injury to identify quantitative trait loci (QTL) responsible for this strain difference. Interval mapping identified two %NIH QTL on rat chromosomes 3 and 6 [logarithm of odds (LOD) scores 2.5, 2.2] and QTL for other injured vascular wall changes on rat chromosomes 3, 4, and 15 (LOD scores 2.0 -4.6). Also, QTL for control vessel media width (MW) and media area (MA) were found on chromosome 6 with LOD scores of 2.3 and 2.5, suggesting that linkage exists between these control vessel parameters and NIH production. These results represent the first genetic analysis for the identification of NIH QTL and QTL associated with the vascular injury response.quantitative trait loci; restenosis; vascular injury; inbred strains; Brown Norway rat; spontaneously hypertensive rat INTERVENTIONS IN THE CARDIOVASCULAR system such as arterial grafts, stents, and balloon angioplasties often fail because of the development of neointimal hyperplasia (NIH). There are no effective therapies to prevent or treat this complication. For example, restenosis secondary to NIH occurs in 30 -40% of patients after balloon angioplasty for coronary artery disease (27). Drug-eluting stents reduce the occurrence of short-term NIH to 20 -30%, but the long-term efficacy of these devices is not known (27). NIH is also associated with the development of significant restenosis in 20% of patients undergoing carotid endarterectomy (1) and is a major contributor to graft failure in coronary and peripheral arteries (24).NIH is triggered by vascular endothelial cell (VEC) disruption and injury that leads to smooth muscle cell (SMC) migration to subendothelial injury sites, followed by SMC proliferation and apoptosis. Significant neointimal thickening and decreased lumen areas are seen within 2 wk after vascular injury (16, 32). However, vascular occlusion can continue after 2 wk as SMC size increases (16, 32) and proteoglycan matrix deposits continue to thicken the neointima (8,28,36,37,45). Many factors are involved in, and possibly responsible for, genetically determined variations in the NIH injury response between different strains of animals and among individual patients (1). We postulate that heritable variations in the genes for these vascular injury response elements are possible candidate...

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Left ventricular function of the isolated, genetically obese rat's heart

Cited by 20 publications

References 0 publications

Diastolic Compliance Is Reduced in Obese Rabbits

Diastolic Compliance Is Reduced in Obese Rabbits

Cardiovascular Abnormalities in Transgenic Mice With Reduced Brown Fat

Linkage analysis of neointimal hyperplasia and vascular wall transformation after balloon angioplasty

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