Determination of the myocardial area at risk after reperfused acute myocardial infarction with different imaging techniques: cardiac magnetic resonance imaging, multidetector computed tomography and histopathological validation

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Cardioprotective effects of shock wave therapy: A cardiac magnetic resonance imaging study on acute ischemia-reperfusion injury

IntroductionCardioprotection strategies remain a new frontier in treating acute myocardial infarction (AMI), aiming at further protect the myocardium from the ischemia-reperfusion damage. Therefore, we aimed at investigating the mechano-transduction effects induced by shock waves (SW) therapy at time of the ischemia reperfusion as a non-invasive cardioprotective innovative approach to trigger healing molecular mechanisms.MethodsWe evaluated the SW therapy effects in an open-chest pig ischemia-reperfusion (IR) model, with quantitative cardiac Magnetic Resonance (MR) imaging performed along the experiments at multiple time points (baseline (B), during ischemia (I), at early reperfusion (ER) (∼15 min), and late reperfusion (LR) (3 h)). AMI was obtained by a left anterior artery temporary occlusion (50 min) in 18 pigs (32 ± 1.9 kg) randomized into SW therapy and control groups. In the SW therapy group, treatment was started at the end of the ischemia period and extended during early reperfusion (600 + 1,200 shots @0.09 J/mm2, f = 5 Hz). The MR protocol included at all time points LV global function assessment, regional strain quantification, native T1 and T2 parametric mapping. Then, after contrast injection (gadolinium), we obtained late gadolinium imaging and extra-cellular volume (ECV) mapping. Before animal sacrifice, Evans blue dye was administrated after re-occlusion for area-at-risk sizing.ResultsDuring ischemia, LVEF decreased in both groups (25 ± 4.8% in controls (p = 0.031), 31.6 ± 3.2% in SW (p = 0.02). After reperfusion, left ventricular ejection fraction (LVEF) remained significantly decreased in controls (39.9 ± 4% at LR vs. 60 ± 5% at baseline (p = 0.02). In the SW group, LVEF increased quickly ER (43.7 ± 11.4% vs. 52.4 ± 8.2%), and further improved at LR (49.4 ± 10.1) (ER vs. LR p = 0.05), close to baseline reference (LR vs. B p = 0.92). Furthermore, there was no significant difference in myocardial relaxation time (i.e. edema) after reperfusion in the intervention group compared to the control group: ΔT1 (MI vs. remote) was increased by 23.2±% for SW vs. +25.2% for the controls, while ΔT2 (MI vs. remote) increased by +24.9% for SW vs. +21.7% for the control group.DiscussionIn conclusion, we showed in an ischemia-reperfusion open-chest swine model that SW therapy, when applied near the relief of 50′ LAD occlusion, led to a nearly immediate cardioprotective effect translating to a reduction in the acute ischemia-reperfusion lesion size and to a significant LV function improvement. These new and promising results related to the multi-targeted effects of SW therapy in IR injury need to be confirmed by further in-vivo studies in close chest models with longitudinal follow-up

Cardioprotective effects of shock wave therapy: A cardiac magnetic resonance imaging study on acute ischemia-reperfusion injury

International audienceIntroduction Cardioprotection strategies remain a new frontier in treating acute myocardial infarction (AMI), aiming at further protect the myocardium from the ischemia-reperfusion damage. Therefore, we aimed at investigating the mechano-transduction effects induced by shock waves (SW) therapy at time of the ischemia reperfusion as a non-invasive cardioprotective innovative approach to trigger healing molecular mechanisms. Methods We evaluated the SW therapy effects in an open-chest pig ischemia-reperfusion (IR) model, with quantitative cardiac Magnetic Resonance (MR) imaging performed along the experiments at multiple time points (baseline (B), during ischemia (I), at early reperfusion (ER) (∼15 min), and late reperfusion (LR) (3 h)). AMI was obtained by a left anterior artery temporary occlusion (50 min) in 18 pigs (32 ± 1.9 kg) randomized into SW therapy and control groups. In the SW therapy group, treatment was started at the end of the ischemia period and extended during early reperfusion (600 + 1,200 shots @0.09 J/mm2, f = 5 Hz). The MR protocol included at all time points LV global function assessment, regional strain quantification, native T1 and T2 parametric mapping. Then, after contrast injection (gadolinium), we obtained late gadolinium imaging and extra-cellular volume (ECV) mapping. Before animal sacrifice, Evans blue dye was administrated after re-occlusion for area-at-risk sizing. Results During ischemia, LVEF decreased in both groups (25 ± 4.8% in controls ( p = 0.031), 31.6 ± 3.2% in SW ( p = 0.02). After reperfusion, left ventricular ejection fraction (LVEF) remained significantly decreased in controls (39.9 ± 4% at LR vs. 60 ± 5% at baseline ( p = 0.02). In the SW group, LVEF increased quickly ER (43.7 ± 11.4% vs. 52.4 ± 8.2%), and further improved at LR (49.4 ± 10.1) (ER vs. LR p = 0.05), close to baseline reference (LR vs. B p = 0.92). Furthermore, there was no significant difference in myocardial relaxation time (i.e. edema) after reperfusion in the intervention group compared to the control group: Δ T1 (MI vs. remote) was increased by 23.2±% for SW vs. +25.2% for the controls, while Δ T2 (MI vs. remote) increased by +24.9% for SW vs. +21.7% for the control group. Discussion In conclusion, we showed in an ischemia-reperfusion open-chest swine model that SW therapy, when applied near the relief of 50′ LAD occlusion, led to a nearly immediate cardioprotective effect translating to a reduction in the acute ischemia-reperfusion lesion size and to a significant LV function improvement. These new and promising results related to the multi-targeted effects of SW therapy in IR injury need to be confirmed by further in-vivo studies in close chest models with longitudinal follow-up

Postconditioning inhibits mPTP opening independent of oxidative phosphorylation and membrane potential

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Postconditioning by Delayed Administration of Ciclosporin A: Implication for Donation after Circulatory Death (DCD)

International audienceHeart transplantation is facing a shortage of grafts. Donation after Circulatory Death (DCD) would constitute a new potential of available organs. In the present work, we aimed to evaluate whether Postconditioning (ischemic or with ciclosporin-A (CsA)) could reduce ischemia-reperfusion injury in a cardiac arrest model when applied at the start of reperfusion or after a delay. An isolated rat heart model was used as a model of DCD. Hearts were submitted to a cardiac arrest of 40 min of global warm ischemia (37 °C) followed by 3 h of 4 °C-cold preservation, then 60 min reperfusion. Hearts were randomly allocated into the following groups: control, ischemic postconditioning (POST, consisting of two episodes each of 30 s ischemia and 30 s reperfusion at the onset of reperfusion), and CsA group (CsA was perfused at 250 nM for 10 min at reperfusion). In respective subgroups, POST and CsA were applied after a delay of 3, 10, and 20 min. Necrosis was lower in CsA and POST versus controls (p < 0.01) whereas heart functions were improved (p < 0.01). However, while the POST lost its efficacy if delayed beyond 3 min of reperfusion, CsA treatment surprisingly showed a reduction of necrosis even if applied after a delay of 3 and 10 min of reperfusion (p < 0.01). This cardioprotection by delayed CsA application correlated with better functional recovery and higher mitochondrial respiratory index. Furthermore, calcium overload necessary to induce mitochondrial permeability transition pore (MPTP) opening was similar in all cardioprotection groups, suggesting a crucial role of MPTP in this delayed protection of DCD hearts

Adaptive noise reduction for power Doppler imaging using SVD filtering in the channel domain and coherence weighting of pixels

International audienceAbstract Objective . Ultrafast power Doppler (UPD) is an ultrasound method that can image blood flow at several thousands of frames per second. In particular, the high number of data provided by UPD enables the use of singular value decomposition (SVD) as a clutter filter for suppressing tissue signal. Notably, is has been demonstrated in various applications that SVD filtering increases significantly the sensitivity of UPD to microvascular flows. However, UPD is subjected to significant depth-dependent electronic noise and an optimal denoising approach is still being sought. Approach . In this study, we propose a new denoising method for UPD imaging: the Coherence Factor Mask (CFM). This filter is first based on filtering the ultrasound time-delayed data using SVD in the channel domain to remove clutter signal. Then, a spatiotemporal coherence mask that exploits coherence information between channels for identifying noisy pixels is computed. The mask is finally applied to beamformed images to decrease electronic noise before forming the power Doppler image. We describe theoretically how to filter channel data using a single SVD. Then, we evaluate the efficiency of the CFM filter for denoising in vitro and in vivo images and compare its performances with standard UPD and with three existing denoising approaches. Main results . The CFM filter gives gains in signal-to-noise ratio and contrast-to-noise ratio of up to 22 dB and 20 dB, respectively, compared to standard UPD and globally outperforms existing methods for reducing electronic noise. Furthermore, the CFM filter has the advantage over existing approaches of being adaptive and highly efficient while not requiring a cut-off for discriminating noise and blood signals nor for determining an optimal coherence lag. Significance . The CFM filter has the potential to help establish UPD as a powerful modality for imaging microvascular flows

Regional myocardial function after myocardial infarction in mice: a follow-up study by strain rate imaging.

International audienceBACKGROUND: New therapeutic strategies aim to reduce the extent of myocardial infarction (MI) to decrease long-term left ventricular (LV) remodeling. These innovations are often developed on murine models of MI and have led to the need for a sensitive tool allowing follow-up. The aim of this study was to investigate by strain rate (SR) imaging early and long-term alteration in regional LV function occurring after MI in mice. METHODS: Echocardiography was serially performed during a 4-month follow-up period in 3 groups of C57BL6 male mice: 7 normal, 5 sham operated, and 27 with left coronary artery ligation (the MI group). In addition to conventional measurements, SR was obtained from short-axis views in the anterior wall and posterior wall (PW). Triphenyltetrazolium chloride staining allowed the localization and measurement of the transmural extent of MI. A transmural MI was defined as an extension > 75% of the wall thickness. RESULTS: In the MI group, LV ejection fractions significantly decreased, while LV dimensions and PW thicknesses increased from baseline to 4 months. On day 3, SR could differentiate transmural from nontransmural (1 +/- 1 vs 10 +/- 1 s(-1); P < .05) and noninfarcted myocardium (25 +/- 1 s(-1)). SR values did not significantly change between day 3 and month 4 and could still differentiate those segments at month 4. Wall thickening was not able to differentiate transmural from nontransmural infarcted segments at day 3 (16 +/- 3% vs 21 +/- 3%; P = NS) or at month 4. CONCLUSION: In this murine model of MI, SR was able to predict the transmural extent of MI as early as 3 days after MI, then remained stable and still differentiated them at 4 months

Dose and timing of injections for effective cyclosporine A pretreatment before renal ischemia reperfusion in mice.

There is experimental evidence that lethal ischemia-reperfusion injury (IRI) is largely due to mitochondrial permeability transition pore (mPTP) opening, which can be prevented by cyclosporine A (CsA). The aim of our study is to show that a higher dose of CsA (10 mg/kg) injected just before ischemia or a lower dose of CsA (3 mg/kg) injected further in advance of ischemia (1 h) protects the kidneys and improves mitochondrial function.All mice underwent a right unilateral nephrectomy followed by 30 min clamping of the left renal artery. Mice in the control group did not receive any pharmacological treatment. Mice in the three groups treated by CsA were injected at different times and with different doses, namely 3 mg/kg 1 h or 10 min before ischemia or 10 mg/kg 10 min before ischemia. After 24 h of reperfusion, the plasma creatinine level were measured, the histological score was assessed and mitochondria were isolated to calculate the calcium retention capacity (CRC) and level of oxidative phosphorylation.Mortality and renal function was significantly higher in the CsA 10 mg/kg-10 min and CsA 3mg/kg-1 h groups than in the CsA 3mg/kg-10 min group. Likewise, the CRC was significantly higher in the former two groups than in the latter, suggesting that the improved renal function was due to a longer delay in the opening of the mPTP. Oxidative phosphorylation levels were also higher 24 h after reperfusion in the protected groups.Our results suggest that the protection afforded by CsA is likely limited by its availability. The dose and timing of the injections are therefore crucial to ensure that the treatment is effective, but these findings may prove challenging to apply in practice

Influence of afterload on left ventricular radial and longitudinal systolic functions: a two-dimensional strain imaging study.

International audienceAIMS: This study aimed to assess the influence of afterload alteration on radial (R) and longitudinal (L) left ventricular (LV) systolic regional functions. METHODS AND RESULTS: We analysed systolic myocardial function by two-dimensional strain (2D-S) and sonomicrometry (SS) in an experimental pig model of aortic banding. Both radial and longitudinal functions were analysed in six open-chest pigs under various loading conditions: baseline and graded aortic banding (subsequent increase in LV pressure of 10, 20, and 40 mmHg). Both systolic 2D-S(long) and 2D-S(rad) were significantly correlated with SS(long) and SS(rad) (r = 0.63, P < 0.001 and r = 0.65, P < 0.01, respectively). At a low increase in LV afterload, 2D-S(rad) was still preserved whereas 2D-S(long) significantly decreased. When LV afterload was subsequently increased, both 2D-S(rad) and 2D-S(long) significantly decreased. Difference in dependence to wall stress might explain these different behaviours. CONCLUSION: 2D-S shows a different response in longitudinal and radial functions to increased afterload. Longitudinal function is early impaired, whereas radial function remains preserved. This finding justifies the combined assessment of both radial and longitudinal regional myocardial functions to characterize myocardial dysfunction and might help to better identify the transition to heart failure in pressure-overload cardiomyopathy