Characterization of right ventricular function after monocrotaline-induced pulmonary hypertension in the intact rat

Hessel, Marleen H. M.; Steendijk, Paul; Adel, Brigit den; Schutte, Cindy I.; Laarse, Arnoud van der

doi:10.1152/ajpheart.00369.2006

Cited by 139 publications

(125 citation statements)

References 48 publications

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“…This concept has been confirmed in aortic banding models (9,36), but it is unclear whether it is applicable to the RV. Previous studies, both experimental and clinical, suggested that in the proximal-type pressure overload, increased contractility rather than Frank-Starling mechanism characterizes the RV response (15,30), whereas in the peripheral-type pressure overload, the RV response is limited to the Frank-Starling mechanism and does not increase contractility (21). By direct comparison, however, this study shows that in both proximal-and peripheral-type pressure overload the RV response uses the Frank-Starling mechanism, but additionally depends on increased contractility for maintaining stroke volume.…”

Section: The Rv Responds To Chronic Pressure Overload With Both Frankmentioning

confidence: 98%

Distinct loading conditions reveal various patterns of right ventricular adaptation

Borgdorff

Bartelds

Dickinson

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Borgdorff MA, Bartelds B, Dickinson MG, Steendijk P, de Vroomen M, Berger RM. Distinct loading conditions reveal various patterns of right ventricular adaptation. Am J Physiol Heart Circ Physiol 305: H354 -H364, 2013. First published May 31, 2013 doi:10.1152/ajpheart.00180.2013.-Right ventricular (RV) failure due to chronically abnormal loading is a main determinant of outcome in pulmonary hypertension (PH) and congenital heart disease. However, distinct types of RV loading have been associated with different outcomes. To determine whether the adaptive RV response depends on loading type, we compared hemodynamics, exercise, and hypertrophy in models of pressure overload due to pulmonary artery banding (PAB), pressure overload due to PH, combined pressure and volume overload, and isolated volume load. Ninety-four rats were subjected to either PAB, monocrotaline-induced PH (PH), aortocaval shunt (shunt), or combined monocrotaline and aortocaval shunt (PH ϩ shunt). We performed pressure-volume analysis and voluntary exercise measurements at 4 wk. We compared PAB to PH (part I) and PH ϩ shunt to either isolated PH or shunt (part II). In part I, enhanced contractility (end-systolic elastance and preload recruitable stroke work) was present in PH and PAB, but strongest in PAB. FrankStarling mechanism was active in both PAB and PH. In PAB this was accompanied by diastolic dysfunction (increased end-diastolic elastance, relaxation constant), clinical signs of RV failure, and reduced exercise. These distinct responses were not attributable to differences in hypertrophy. In part II, in PH ϩ shunt the contractility response was blunted compared with PH, which caused pseudonormalization of parameters. Additional volume overload strongly enhanced hypertrophy in PH. We conclude that different types of loading result in distinct patterns of RV adaptation. This is of importance for the approach to patients with chronically increased RV load and for experimental studies in various types of RV failure. right ventricular failure; contractility; pressure-volume analysis; pulmonary hypertension; monocrotaline RIGHT VENTRICULAR FAILURE is a detrimental condition that is associated with significant morbidity and mortality in patients with congenital heart disease and/or pulmonary hypertension (PH) (11,19,34,38). In these conditions, persistent abnormal loading of the right ventricle (RV) leads to RV failure in the long term (17, 50). However, physiological and molecular mechanisms of RV adaptation to these abnormal loading conditions and its derailment into RV failure are largely unknown (3, 50). As a consequence, no heart failure therapy exists that specifically targets the RV. Different animal models have been used to study the abnormally loaded RV, but interpretation of data and translation to the clinical setting are hampered by conceptual concerns.First, distinct types of RV overload are used in experimental models. These include the induction of PH, where the RV interacts with an increased dynamic load due to a highresistance p...

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Section: The Rv Responds To Chronic Pressure Overload With Both Frankmentioning

confidence: 98%

Distinct loading conditions reveal various patterns of right ventricular adaptation

Borgdorff

Bartelds

Dickinson

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…A repeat cardiac catheterization after six months of therapy showed a mild decrease in PAP to 64/39 mmHg, and an increase in cardiac index to 2.6 l/min/m 2 . (Hessel et al, 2006). MCT-induced PH varies among strains and species of animals.…”

Section: Case Studymentioning

confidence: 99%

Idiopathic pulmonary arterial hypertension

Firth

Mandel

Yuan

2010

Disease Models &Amp; Mechanisms

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Despite improved understanding of the pathobiology of pulmonary arterial hypertension (PAH), it remains a severe and progressive disease, usually culminating in right heart failure, significant morbidity and early mortality. Over the last decade, some major advances have led to substantial improvements in the management of PAH. Much of this progress was pioneered by work in animal models. Although none of the current animal models of pulmonary hypertension (PH) completely recapitulate the human disease, they do provide insight into the cellular pathways contributing to its development and progression. There is hope that future work in model organisms will help to define its underlying cause(s), identify risk factors and lead to better treatment of the currently irreversible damage that results in the lungs of afflicted patients. However, the difficulty in defining the etiology of idiopathic PAH (IPAH, previously known as primary pulmonary hypertension) makes this subset of the disease particularly difficult to model. Although there are some valuable existing models that are relevant for IPAH research, the area would value from the development of new models that more closely mimic the clinical pathophysiology of IPAH.

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“…Many experimental animal models of PAH exist and this includes monocrotaline (MCT)-induced and chronic hypoxiainduced rats (9)(10)(11). Although the precise mechanism by which MCT leads to PAH is unknown, the MCT-induced PAH model is a mainstay in evaluating experiments of new therapeutic interventions.…”

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confidence: 99%

Modafinil improves monocrotaline-induced pulmonary hypertension rat model

et al. 2016

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Background: Pulmonary arterial hypertension (PAH) progressively leads to increases in pulmonary vasoconstriction. Modafinil plays a role in vasorelaxation and blocking KCa3.1 channel with a result of elevating intracellular cyclic adenosine monophosphate (cAMP) levels. The purpose of this study is to evaluate the effects on modafinil in monocrotaline (MCT)-induced PAH rat. Methods: The rats were separated into three groups: the control group, the monocrotaline (M) group (MCT 60 mg/kg), and the modafinil (MD) group (MCT 60 mg/kg + modafinil). results: Reduced right ventricular pressure (RVP) was observed in the MD group. Right ventricular hypertrophy was improved in the MD group. Reduced number of intra-acinar pulmonary arteries and medial wall thickness were noted in the MD group. After the administration of modafinil, protein expressions of endothelin-1 (ET-1), endothelin receptor A (ERA) and KCa3.1 channel were significantly reduced. Modafinil suppressed pulmonary artery smooth muscle cell (PASMC) proliferation via cAMP and KCa3.1 channel. Additionally, we confirmed protein expressions such as Bcl-2-associated X, vascular endothelial growth factor, tumor necrosis factor-α, and interleukin-6 were reduced in the MD group. conclusion: Modafinil improved PAH by vasorelaxation and a decrease in medial thickening via ET-1, ERA, and KCa3.1 down regulation. This is a meaningful study of a modafinil in PAH model.

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Characterization of right ventricular function after monocrotaline-induced pulmonary hypertension in the intact rat

Cited by 139 publications

References 48 publications

Distinct loading conditions reveal various patterns of right ventricular adaptation

Distinct loading conditions reveal various patterns of right ventricular adaptation

Idiopathic pulmonary arterial hypertension

Modafinil improves monocrotaline-induced pulmonary hypertension rat model

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