A model of chronic heart failure in spontaneous hypertensive rats                (SHR)

“…Although susceptible to preload and afterload conditions in general, the peak rate of increase and decrease in LV pressure (LV dP/dt max and dP/dt min ) represents contractile and diastolic performance, respectively [9]. Additionally, significant declines in fractional shortening (FS) and ejection fraction (EF)-both expressed in percentage values-indicate systolic dysfunction; progressive decreases are prognostic of decompensation and death from HF [23]. For instance, in a large human cohort study, every incremental 5% decrease in EF below 45% corresponded with a 15% increase in risk of death within 2 years [24].…”

Section: Functional Structural and Hemodynamic Indicatorsmentioning

confidence: 99%

Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure

et al. 2011

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Heart failure (HF) is characterized as a limitation to cardiac output that prevents the heart from supplying tissues with adequate oxygen and predisposes individuals to pulmonary edema. Impaired cardiac function is secondary to either decreased contractility reducing ejection (systolic failure), diminished ventricular compliance preventing filling (diastolic failure), or both. To study HF etiology, many different techniques have been developed to elicit this condition in experimental animals, with varying degrees of success. Among rats, surgically induced HF models are the most prevalent, but they bear several shortcomings, including high mortality rates and limited recapitulation of the pathophysiology, etiology, and progression of human HF. Alternatively, a number of non-invasive HF induction methods avoid many of these pitfalls, and their merits in technical simplicity, reliability, survivability, and comparability to the pathophysiologic and pathogenic characteristics of HF are reviewed herein. In particular, this review focuses on the primary pathogenic mechanisms common to genetic strains (spontaneously hypertensive and spontaneously hypertensive heart failure), pharmacological models of toxic cardiomyopathy (doxorubicin and isoproterenol), and dietary salt models, all of which have been shown to induce left ventricular HF in the rat. Additional non-invasive techniques that may potentially enable the development of new HF models are also discussed.

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“…Permanent occlusion of the left coronary artery close to its origin from the aorta was performed with male Sprague Dawley rats as described [18] . The day after the surgery, animals were randomized in 6 groups and treatment with AVE8134 (1, 3, and 10 mg·kg -1 ·d -1 pressed in chow) started.…”

Section: Myocardial Infarction Induced By Permanent Coronary Ligationmentioning

confidence: 99%

The peroxisome proliferator-activated receptor-α (PPAR-α) agonist, AVE8134, attenuates the progression of heart failure and increases survival in rats

Linz

Wohlfart

Baader³

et al. 2009

Acta Pharmacol Sin

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Aim: To investigate the efficacy of the peroxisome proliferator-activated receptor-α (PPARα) agonist, AVE8134, in cellular and experimental models of cardiac dysfunction and heart failure. Methods: In Sprague Dawley rats with permanent ligation of the left coronary artery (post-MI), AVE8134 was compared to the PPARγ agonist rosiglitazone and in a second study to the ACE inhibitor ramipril. In DOCA-salt sensitive rats, efficacy of AVE8134 on cardiac hypertrophy and fibrosis was investigated. Finally, AVE8134 was administered to old spontaneously hypertensive rats (SHR) at a nonblood pressure lowering dose with survival as endpoint. In cellular models, we studied AVE8134 on hypertrophy in rat cardiomyocytes, nitric oxide signaling in human endothelial cells (HUVEC) and LDL-uptake in human MonoMac-6 cells. Results: In post-MI rats, AVE8134 dose-dependently improved cardiac output, myocardial contractility and relaxation and reduced lung and left ventricular weight and fibrosis. In contrast, rosiglitazone exacerbated cardiac dysfunction. Treatment at AVE8134 decreased plasma proBNP and arginine and increased plasma citrulline and urinary NOx/creatinine ratio. In DOCA rats, AVE8134 prevented development of high blood pressure, myocardial hypertrophy and cardiac fibrosis, and ameliorated endothelial dysfunction. Compound treatment increased cardiac protein expression and phosphorylation of eNOS. In old SHR, treatment with a low dose of AVE8134 improved cardiac and vascular function and increased life expectancy without lowering blood pressure. AVE8134 reduced phenylephrine-induced hypertrophy in adult rat cardiomyocytes. In HUVEC, Ser-1177-eNOS phosphorylation but not eNOS expression was increased. In monocytes, AVE8134 increased the expression of CD36 and the macrophage scavenger receptor 1, resulting in enhanced uptake of oxidized LDL. Conclusion: The PPARα agonist AVE8134 prevents post-MI myocardial hypertrophy, fibrosis and cardiac dysfunction. AVE8134 has beneficial effects against hypertension-induced organ damages, resulting in decreased mortality. The compound exerts its protective properties by a direct effect on cardiomyocyte hypertrophy, but also indirectly via monocyte signaling and increased endothelial NO production.

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A model of chronic heart failure in spontaneous hypertensive rats (SHR)

Cited by 25 publications

References 24 publications

Animal Models of Heart Failure

Animal Models of Heart Failure

Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure

The peroxisome proliferator-activated receptor-α (PPAR-α) agonist, AVE8134, attenuates the progression of heart failure and increases survival in rats

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