American journal of physiology. Heart and circulatory physiology
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Am. J. Physiol. Heart Circ. Physiol. · Oct 2011
Apelin-13 protects the heart against ischemia-reperfusion injury through inhibition of ER-dependent apoptotic pathways in a time-dependent fashion.
Endoplasmic reticulum (ER) stress is activated during and contributes to ischemia-reperfusion (I/R) injury. Attenuation of ER stress-induced apoptosis protects the heart against I/R injury. Using apelin, a ligand used to activate the apelin APJ receptor, which is known to be cardioprotective, this study was designed to investigate 1) the time course of changes in I/R injury after ER stress; 2) whether apelin infusion protects the heart against I/R injury via modulation of ER stress-dependent apoptosis signaling pathways; and 3) how phosphatidylinositol 3-kinase (PI3K)/Akt, endothelial nitric oxide synthase (eNOS), AMP-activated protein kinase (AMPK), and ERK activation are involved in the protection offered by apelin treatment. ⋯ Administration of apelin at 1 μg/kg not only completely abolished the activation of ER stress-induced apoptosis signaling pathways at 2 h of reperfusion but also significantly attenuated time-related changes at 24 h of reperfusion. Using pharmacological inhibition, we also demonstrated that PI3K/Akt, AMPK, and ERK activation were involved in the protection against I/R injury via inhibition of ER stress-dependent apoptosis activation. In contrast, although eNOS activation played a role in decreasing IS at 2 h of reperfusion, it failed to modify either IS or ER stress-induced apoptosis signaling pathways at 24 h after reperfusion.
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Am. J. Physiol. Heart Circ. Physiol. · Sep 2011
Multicenter StudyEvidence for greater burden of peripheral arterial disease in lower extremity arteries of spinal cord-injured individuals.
Spinal cord injury leads to increased risk for cardiovascular disease and results in greater risk of death. Subclinical markers of atherosclerosis have been reported in carotid arteries of spinal cord-injured individuals (SCI), but the development of lower extremity peripheral arterial disease (PAD) has not been investigated in this population. The purpose of this study was to determine the effect of spinal cord injury on ankle-brachial index (ABI) and intima-media thickness (IMT) of upper-body and lower-extremity arteries. ⋯ Lower extremity IMTs revealed similar thicknesses for both superficial femoral and popliteal arteries, but when normalized for artery diameter, individuals with SCI had greater IMT than controls in the superficial femoral (0.094 ± 0.03 vs. 0.073 ± 0.02 mm/mm lumen diameter, P < 0.01) and popliteal (0.117 ± 0.04 vs. 0.091 ± 0.02 mm/mm lumen diameter, P < 0.01) arteries. The ABI and normalized IMT of SCI compared with controls indicate that subclinical measures of lower-extremity PAD are worsened in individuals with SCI. These findings should prompt physicians to consider using the ABI as a screening method to detect lower-extremity PAD in SCI.
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Am. J. Physiol. Heart Circ. Physiol. · Sep 2011
Comparative StudyValidation of a patient-specific one-dimensional model of the systemic arterial tree.
The aim of this study is to develop and validate a patient-specific distributed model of the systemic arterial tree. This model is built using geometric and hemodynamic data measured on a specific person and validated with noninvasive measurements of flow and pressure on the same person, providing thus a patient-specific model and validation. The systemic arterial tree geometry was obtained from MR angiographic measurements. ⋯ The model predicts pressure and flow waveforms in good qualitative and quantitative agreement with the in vivo measurements, in terms of wave shape and specific wave features. Comparison with a generic one-dimensional model shows that the patient-specific model better predicts pressure and flow at specific arterial sites. These results obtained let us conclude that a patient-specific one-dimensional model of the arterial tree is able to predict well pressure and flow waveforms in the main systemic circulation, whereas this is not always the case for a generic one-dimensional model.
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Am. J. Physiol. Heart Circ. Physiol. · Sep 2011
Comparative StudyA three-dimensional insight into the complexity of flow convergence in mitral regurgitation: adjunctive benefit of anatomic regurgitant orifice area.
Mitral effective regurgitant orifice area (EROA) using the flow convergence (FC) method is used to quantify the severity of mitral regurgitation (MR). However, it is challenging and prone to interobserver variability in complex valvular pathology. We hypothesized that real-time three-dimensional (3D) transesophageal echocardiography (RT3D TEE) derived anatomic regurgitant orifice area (AROA) can be a reasonable adjunct, irrespective of valvular geometry. ⋯ However, in patients with eccentric MR, the bias was larger than in central MR. Intermeasurement variability was higher for the 2D FC technique than for RT3DE-based measurements. With its superior reproducibility, 3D analysis of the AROA is a useful alternative to quantify MR when 2D FC measurements are challenging.
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Current rodent models of ischemia/infarct or pressure-volume overload are not fully representative of human heart failure. We developed a new model of congestive heart failure (CHF) with both ischemic and stress injuries combined with fibrosis in the remote myocardium. Sprague-Dawley male rats were used. ⋯ Perivascular fibrosis in remote myocardium after Ab + I/R + DeAb was associated with decreased cardiac function. We conclude that Ab plus I/R injury with aortic DeAb represents a novel model of CHF with increased fibrosis in remote myocardium. This model will allow the investigation of vascular and fibrotic mechanisms in CHF characterized by low EF, dilated LV, moderate infarction, near-normal aortic diameter, and reperfused coronary arteries.