Pathophysiology of Contractile Dysfunction in Heart Failure

Dhalla, Naranjan S.; Wang, Jingwei; Guo, Xiaobing

doi:10.1007/978-0-585-29191-8_1

Cited by 1 publication

(1 citation statement)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nonetheless, on the basis of an association of antihypertrophic action of both SAR and CIL with improved cardiac function of the infarcted animals, it can be argued that the improvement in cardiac performance by these agents may be due to a reduction in the extent of cardiac hypertrophy. However, such a view is in contrast to the general concept that cardiac hypertrophy is beneficial in compensating cardiac function due to the loss of viable myocardium in the infarcted heart [45]. On the other hand, cardiac hypertrophy over a prolonged period is known to exert deleterious action on heart function as a consequence of subcellular remodelling under different pathophysiological conditions [9,10] and the beneficial effect of SAR and CIL on cardiac function may be due to attenuation of subcellular remodelling.…”

Section: Sar and Cil As Antiplatelet Agents In Chfmentioning

confidence: 99%

Antiplatelet therapy attenuates subcellular remodelling in congestive heart failure

Sanganalmath

Babick

Barta

et al. 2008

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

Antiplatelet agents, sarpogrelate (SAR), a 5-HT2A receptor antagonist, and cilostazol (CIL), a phosphodiesterase III (PDE-III) inhibitor, are used for the treatment of peripheral vascular disease. We tested whether these agents affect cardiac function and subcellular remodelling in congestive heart failure (CHF) induced by myocardial infarction (MI). Three weeks after MI, rats were treated daily with 5 mg/kg SAR or CIL as well as vehicle for 5 weeks. Sham-operated animals served as controls. At end of the treatment period, haemodynamic measurements were performed and the left ventricle was processed for the determination of sarcoplasmic reticulum (SR) Ca2+-uptake and -release activities, and expression of SR Ca2+-pump, phospholamban and ryanodine receptors, as well as myofibrillar ATPase activities, expression of α- and β-myosin heavy chain (MHC) isoforms, and phosphorylation of phospholamban and cardiac troponin-I (c Tn-I). Marked haemodynamic changes in the MI-induced CHF were associated with depressions in SR Ca +-uptake and -release activities as well as in protein content and gene expression for SR proteins. Furthermore, myofibrillar Ca2+-stimulated ATPase activity, as well as protein content and gene expression for α-MHC were decreased whereas those for β-MHC were increased in the failing heart. Also, phosphorylation levels of phospholamban and cTn-I were reduced in failing hearts. The MI-associated changes in cardiac function, SR and myofibillar activities, as well as SR and myofibrillar protein and gene expression were attenuated by treatment with SAR or CIL. The results suggest that SAR and CIL improve cardiac function by ameliorating subcellular remodelling in the failing heart and indicate the potential therapy of CHF with antiplatelet agents.

show abstract

Section: Sar and Cil As Antiplatelet Agents In Chfmentioning

confidence: 99%