Contractility and Pump Function of In Vivo Left Ventricle and Its Coupling with Arterial Load: Testing the Assumptions

Author(s):  
Kiichi Sagawa ◽  
David A. Kass ◽  
Seiryo Sugiura ◽  
Daniel Burkhoff ◽  
Joe Alexander
2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Irene Cuadrado ◽  
Maria Jose Garcia Miguel ◽  
Irene Herruzo ◽  
Mari Carmen Turpin ◽  
Ana Martin ◽  
...  

Extracellular matrix metalloproteinase inducer EMMPRIN, is highly expressed in patients with acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including MMP-9 and MMP-13. To prevent Extracellular matrix degradation and cardiac cell death we targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles with an EMMPRIN binding peptide AP9 conjugated (NAP9), or an AP9 scramble peptide as a negative control (NAPSC). NAP9 binds to endogenous EMMPRIN as detected by confocal microscopy of cardiac myocytes and macrophages incubated with NAP and NAPSC in vitro, and in vivo in mouse hearts subjected to left anterior descending coronary artery occlusion (IV injection 50mγ/Kg NAP9 or NAP9SC). Administration of NAP9 at the same time or 1 hour after AMI reduced infarct size over a 20% respect to untreated and NAPSC injected mice, recovered left ventricle ejection fraction (LVEF) similar to healthy controls, and reduced EMMPRIN downstream MMP9 expression. In magnetic resonance scans of mouse hearts 2 days after AMI and injected with NAP9, we detected a significant gadolinium enhancement in the left ventricle respect to non-injected mice and to mice injected with NAPSC. Late gadolinium enhancement assays exhibited NAP9-mediated left ventricle signal enhancement as early as 30 minutes after nanoprobe injection, in which a close correlation between the MRI signal enhancement and left ventricle infarct size was detected. Taken together, these results point EMMPRIN targeted nanoprobes as a new tool for the treatment of AMI.


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Liudmila Zakharova ◽  
Hikmet Nural ◽  
James R Nimlos ◽  
Snjezana Popovic ◽  
Lorraine Feehery ◽  
...  

A pilot clinical study using autologous c-Kit+ cells showed improvement in cardiac functions in congestive heart failure (CHF), however, it is unclear if c-Kit+ cells isolated from CHF hearts are equally as potent as cells from controls. To test the potency of CHF c-Kit+ cells, myocardial infarction (MI) was created by permanent ligation of the left anterior descending coronary artery. Six weeks after MI, animals with left ventricle end-diastolic pressure (LVEDP) ≥20 mmHg and scar size ≥30% of left ventricle (LV) were designated as CHF rats. We found that CHF atrial explants generated less c-Kit+ cells compared to shams (15.7% vs. 11% sham vs. CHF). CHF c-Kit+ cells exhibited elevated levels of epicardial to mesenchymal transition markers, including Snail (2.5 fold) and Pai1 (3 fold), while the expression level of epithelial marker, E-cadherin was 3 fold lower in CHF c-Kit+ cells. Moreover, CHF c-Kit+ cells exhibited reduced gene expressions of pluripotency markers; 2.1 fold decrease in Nanog and 4.5 fold decrease in Sox 2 compared to sham cells. To evaluate the potency of the c-Kit+ cells, 1 x 10 6 cells isolated from CHFs or shams were delivered to 3 weeks post-MI CHF hearts. Cells were pre-labeled with GFP to enable their tracing in vivo and delivered to the infarcted myocardium via left coronary vein by a retrograde coronary sinus cell infusion (RCI). RCI delivery resulted in a cell distribution of LV (30%), right atrium (30%) and right ventricle (20%), while only 10% of cells were found in a left atrium. Three weeks after cells delivery, rats transplanted with sham c-Kit+ cells showed improved LVEDP (29.4 ± 6 vs. 11.7 ± 3.5 mmHg, CHF vs. CHF+ sham c-Kit+ cells) and a rise in peak rate of pressure (dPdt max) (3988 ± 520 vs. 5333 ± 597 mmHg/s). In contrast, no functional improvement was detected in rats transplanted with CHF c-Kit+ cells. Histological analysis demonstrated that transplanted c-Kit+/GFP+ cells were mostly incorporated into blood vessels and co-localized with endothelial marker vWf, and α-smooth muscle actin. Our results showed that left coronary vein is an efficient route for c-Kit+ cell delivery and that c-Kit+ cells isolated from CHF rats are less potent when transplanted in chronic heart failure rat model compared to those isolated from control.


2016 ◽  
Vol 18 (5) ◽  
Author(s):  
Kyle Fricke ◽  
Filip Konecny ◽  
Alexander El-Warrak ◽  
Chad Hodgson ◽  
Heather Cadieux-Pitre ◽  
...  

Circulation ◽  
2005 ◽  
Vol 112 (9_supplement) ◽  
Author(s):  
Tomasz A. Timek ◽  
Julie R. Glasson ◽  
David T. Lai ◽  
David Liang ◽  
George T. Daughters ◽  
...  

Background— A “saddle-shaped” mitral annulus with an optimal ratio between annular height and commissural diameter may reduce leaflet and chordal stress and is purported to be conserved across mammalian species. Whether annuloplasty rings maintain this relationship is unknown. Methods and Results— Twenty-three adult sheep underwent implantation of radiopaque markers on the left ventricle and mitral annulus. Eight animals underwent implantation of a Carpentier-Edwards Physio ring, 7 underwent a Medtronic Duran flexible ring, and 8 served as controls. Animals were studied with biplane videofluoroscopy 7 to 10 days postoperatively. Annular height and commissural width (CW) were determined from 3D marker coordinates, and annular height:CW ratio (AHWCR) was calculated. Annular height was similar in Control and Duran animals but significantly lower in the Physio group at end diastole (8.4±3.8, 6.7±2.3, and 3.4±0.6 mm, respectively, for Control, Duran, and Physio; ANOVA=0.005) and at end systole (14.5±6.2, 10.5±5.5, and 5.8±2.5 mm, respectively, for Control, Duran, and Physio; ANOVA=0.004). Both ring groups reduced CW significantly relative to Control. AHCWR did not differ between Control and Duran but was lower in Physio (23±11%, 24±7%, and 12±2% at end diastole and 42±17%, 37±17%, and 21±10% at end systole, respectively, for Control, Duran, and Physio, respectively; ANOVA <0.05 for both). Conclusions— Mitral annular height and AHWCR of the native valve were unchanged by a Duran ring, whereas the Physio ring led to a lower AHWCR. Theoretically, such a flexible annuloplasty ring may provide better leaflet stress distribution by maintaining normal AHWCR.


Author(s):  
Peter L. M. Kerkhof ◽  
Arjan D. Van Dijk ◽  
Tjong Aouw Jong ◽  
Jan Koops ◽  
Rudolf J. Moene ◽  
...  
Keyword(s):  

2019 ◽  
Vol 141 (9) ◽  
Author(s):  
Yaghoub Dabiri ◽  
Kevin L. Sack ◽  
Nuno Rebelo ◽  
Peter Wang ◽  
Yunjie Wang ◽  
...  

We sought to calibrate mechanical properties of left ventricle (LV) based on three-dimensional (3D) speckle tracking echocardiographic imaging data recorded from 16 segments defined by American Heart Association (AHA). The in vivo data were used to create finite element (FE) LV and biventricular (BV) models. The orientation of the fibers in the LV model was rule based, but diffusion tensor magnetic resonance imaging (MRI) data were used for the fiber directions in the BV model. A nonlinear fiber-reinforced constitutive equation was used to describe the passive behavior of the myocardium, whereas the active tension was described by a model based on tissue contraction (Tmax). isight was used for optimization, which used abaqus as the forward solver (Simulia, Providence, RI). The calibration of passive properties based on the end diastolic pressure volume relation (EDPVR) curve resulted in relatively good agreement (mean error = −0.04 ml). The difference between the experimental and computational strains decreased after segmental strain metrics, rather than global metrics, were used for calibration: for the LV model, the mean difference reduced from 0.129 to 0.046 (circumferential) and from 0.076 to 0.059 (longitudinal); for the BV model, the mean difference nearly did not change in the circumferential direction (0.061) but reduced in the longitudinal direction from 0.076 to 0.055. The calibration of mechanical properties for myocardium can be improved using segmental strain metrics. The importance of realistic fiber orientation and geometry for modeling of the LV was shown.


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