American journal of physiology. Heart and circulatory physiology
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Am. J. Physiol. Heart Circ. Physiol. · May 2008
Angiopoietin-1 inhibits intrinsic apoptotic signaling and vascular hyperpermeability following hemorrhagic shock.
Studies from our laboratory demonstrated the involvement of intrinsic apoptotic signaling in hyperpermeability following hemorrhagic shock (HS). Angiopoietin 1 (Ang-1), a potent inhibitor of hyperpermeability, was recently shown to inhibit apoptosis. The purpose of our study was to determine the effectiveness of Ang-1 in attenuating HS-induced hyperpermeability and its relationship to apoptotic signaling. ⋯ Ang-1 attenuated HS and BAK (BH3) peptide-induced collapse of DeltaPsi(m), smac release, cytochrome c release, activation of caspase-3, and vascular hyperpermeability. In vivo, BAK (BH3) induced vascular hyperpermeability that was attenuated by Ang-1 (P < 0.05). These findings suggest that Ang-1's role in maintaining microvascular endothelial barrier integrity involves the intrinsic apoptotic signaling cascade.
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Am. J. Physiol. Heart Circ. Physiol. · May 2008
Progressive nature of chronic mitral regurgitation and the role of tissue Doppler-derived indexes.
The aim of this study was to determine whether severe mitral regurgitation (MR) is progressive and whether tissue-Doppler (TD)-derived indexes can detect early left ventricular (LV) dysfunction in chronic severe MR. Percutaneous rupture of mitral valve chordae was performed in pigs (n = 8). Before MR (baseline), immediately after MR (post-MR), and at 1 and 3 mo after MR, cardiac function was assessed using conventional and TD-derived indexes. ⋯ With the increase in LV dimensions, the forward stroke volume remained unchanged, but the mitral annular dimensions, EROA, and regurgitant fraction increased (EROA = 41 +/- 2 and 51 +/- 2 mm(2) post-MR and at 3 mo, respectively, P < 0.01). Peak systolic myocardial velocities, strain, and strain rate increased acutely post-MR and remained elevated at 1 mo but declined by 3 mo (anterior strain rate = 2.9 +/- 0.1 and 2.4 +/- 0.2 s(-1) post-MR and at 3 mo, respectively, P < 0.001). Therefore, in a chronic model of MR, serial echocardiography demonstrated that MR begets MR and that those TD-derived indexes that initially increased post-MR decreased to baseline before any changes in LV ejection fraction.