MI Size Research Articles

Full left ventricular coverage is essential for the accurate quantification of the area-at-risk by T1 and T2 mapping

T2-weighted cardiovascular magnetic resonance (CMR) using a 3-slice approach has been shown to accurately quantify the edema-based area-at-risk (AAR) in ST-segment elevation myocardial infarction (STEMI). We aimed to compare the performance of a 3-slice approach to full left ventricular (LV) coverage for the AAR by T1 and T2 mapping and MI size. Forty-eight STEMI patients were prospectively recruited and underwent a CMR at 4 ± 2 days. There was no difference between the AARfull LV and AAR3-slices by T1 (P = 0.054) and T2-mapping (P = 0.092), with good correlations but small biases and wide limits of agreements (T1-mapping: N = 30, R2 = 0.85, bias = 1.7 ± 9.4% LV; T2-mapping: N = 48, R2 = 0.75, bias = 1.7 ± 12.9% LV). There was also no significant difference between MI size3-slices and MI sizefull LV (P = 0.93) with an excellent correlation between the two (R2 0.92) but a small bias of 0.5% and a wide limit of agreement of ±7.7%. Although MSI was similar between the 2 approaches, MSI3-slices performed poorly when MSI was <0.50. Furthermore, using AAR3-slices and MI sizefull LV resulted in ‘negative’ MSI in 7/48 patients. Full LV coverage T1 and T2 mapping are more accurate than a 3-slice approach for delineating the AAR, especially in those with MSI < 0.50 and we would advocate full LV coverage in future studies.

Quantifying the area-at-risk of myocardial infarction in-vivo using arterial spin labeling cardiac magnetic resonance

T2-weighted cardiovascular magnetic resonance (T2-CMR) of myocardial edema can quantify the area-at-risk (AAR) following acute myocardial infarction (AMI), and has been used to assess myocardial salvage by new cardioprotective therapies. However, some of these therapies may reduce edema, leading to an underestimation of the AAR by T2-CMR. Here, we investigated arterial spin labeling (ASL) perfusion CMR as a novel approach to quantify the AAR following AMI. Adult B6sv129-mice were subjected to in vivo left coronary artery ligation for 30 minutes followed by 72 hours reperfusion. T2-mapping was used to quantify the edema-based AAR (% of left ventricle) following ischemic preconditioning (IPC) or cyclosporin-A (CsA) treatment. In control animals, the AAR by T2-mapping corresponded to that delineated by histology. As expected, both IPC and CsA reduced MI size. However, IPC, but not CsA, also reduced myocardial edema leading to an underestimation of the AAR by T2-mapping. In contrast, regions of reduced myocardial perfusion delineated by cardiac ASL were able to delineate the AAR when compared to both T2-mapping and histology in control animals, and were not affected by either IPC or CsA. Therefore, ASL perfusion CMR may be an alternative method for quantifying the AAR following AMI, which unlike T2-mapping, is not affected by IPC.

Reperfusion ventricular arrhythmia bursts identify larger infarct size in spite of optimal epicardial and microvascular reperfusion using cardiac magnetic resonance imaging.

Ventricular arrhythmia (VA) bursts following recanalisation in acute ST-elevation myocardial infarction (STEMI) are related to larger infarct size (IS). Inadequate microvascular reperfusion, as determined by microvascular obstruction (MVO) using cardiac magnetic resonance imaging (CMR), is also known to be associated with larger IS. This study aimed to test the hypothesis that VA bursts identify larger infarct size in spite of optimal microvascular reperfusion. All 65 STEMI patients from the Maastricht ST elevation (MAST) study with brisk epicardial flow (TIMI 3), complete ST recovery post-percutaneous coronary intervention and early CMR were included. Using 24-hour Holter registrations from the time of admission, VA bursts were identified against subject-specific Holter background VA rates using a statistical outlier method. MVO and final IS were determined using delayed enhancement CMR. MVO was present in 37/65 (57%) of patients. IS was significantly smaller in the group without MVO (median 9.4% vs. 20.5%; p < 0.001). IS in the group with MVO did not differ depending on VA burst ( n = 28/37; median 20.8% vs. 19.7%; p = 0.64). However, in the group without MVO, VA burst was associated with significantly larger IS ( n = 17/28; median 10.5% vs. 4.1%; p = 0.037). In multivariable analyses, VA burst as well as anterior infarct location remained independent predictors of larger infarct size. In the presence of suboptimal reperfusion with MVO by CMR, VA burst does not further define MI size. However, with optimal TIMI 3 reperfusion and optimal microvascular perfusion (i.e. no MVO), VA burst is associated with larger IS, indicating that VA burst is a marker of additional cell death.

Quantification of both the area-at-risk and acute myocardial infarct size in ST-segment elevation myocardial infarction using T1-mapping

BackgroundA comprehensive cardiovascular magnetic resonance (CMR) in reperfused ST-segment myocardial infarction (STEMI) patients can be challenging to perform and can be time-consuming. We aimed to investigate whether native T1-mapping can accurately delineate the edema-based area-at-risk (AAR) and post-contrast T1-mapping and synthetic late gadolinium (LGE) images can quantify MI size at 1.5 T. Conventional LGE imaging and T2-mapping could then be omitted, thereby shortening the scan duration.MethodsTwenty-eight STEMI patients underwent a CMR scan at 1.5 T, 3 ± 1 days following primary percutaneous coronary intervention. The AAR was quantified using both native T1 and T2-mapping. MI size was quantified using conventional LGE, post-contrast T1-mapping and synthetic magnitude-reconstructed inversion recovery (MagIR) LGE and synthetic phase-sensitive inversion recovery (PSIR) LGE, derived from the post-contrast T1 maps.ResultsNative T1-mapping performed as well as T2-mapping in delineating the AAR (41.6 ± 11.9% of the left ventricle [% LV] versus 41.7 ± 12.2% LV, P = 0.72; R2 0.97; ICC 0.986 (0.969–0.993); bias −0.1 ± 4.2% LV). There were excellent correlation and inter-method agreement with no bias, between MI size by conventional LGE, synthetic MagIR LGE (bias 0.2 ± 2.2%LV, P = 0.35), synthetic PSIR LGE (bias 0.4 ± 2.2% LV, P = 0.060) and post-contrast T1-mapping (bias 0.3 ± 1.8% LV, P = 0.10). The mean scan duration was 58 ± 4 min. Not performing T2 mapping (6 ± 1 min) and conventional LGE (10 ± 1 min) would shorten the CMR study by 15–20 min.ConclusionsT1-mapping can accurately quantify both the edema-based AAR (using native T1 maps) and acute MI size (using post-contrast T1 maps) in STEMI patients without major cardiovascular risk factors. This approach would shorten the duration of a comprehensive CMR study without significantly compromising on data acquisition and would obviate the need to perform T2 maps and LGE imaging.

Early or late intervention in patients with transient ST-segment elevation acute coronary syndrome: Subgroup analysis of the ELISA-3 trial.

To investigate incidence and patient characteristics of transient ST-segment elevation (TSTE) ACS and to compare outcome of early versus late invasive treatment. Optimal timing of treatment in TSTE-ACS patients is not outlined in current guidelines and no prospective randomized trials have been done so far. Post hoc subgroup analysis of patients with TSTE randomized in the ELISA 3 trial. This study compared early (<12 h) versus late (>48 h) angiography and revascularization in 542 patients with high-risk NSTE-ACS. Primary endpoint was incidence of death, reinfarction, or recurrent ischemia at 30 days follow-up. TSTE was present in 129 patients (24.2%) and associated with male gender, smoking and younger age. The primary endpoint occurred in 8.9% of patients with and 13.0% of patients without TSTE (RR = 0.681, P = 0.214). Incidence of death or MI after 2 year follow-up was 5.7 and 14.6% respectively (RR = 0.384, P = 0.008). Within the group of patients with TSTE, incidence of the primary endpoint was 5.8% in the early and 12.7% in the late treatment group (RR = 0.455, P = 0.213), driven by reduction in recurrent ischemia. Enzymatic infarct size, bleeding and incidence of death or recurrent MI at 2 years follow-up was comparable between the treatment groups. In high-risk patients with NSTE-ACS, TSTE is frequently seen. Similar to findings in patients with high-risk NSTE-ACS, immediate angiography and revascularization in these patients is feasible but not superior to later treatment. Prospective randomized trials are needed to provide more evidence in the optimal timing of treatment in patients with TSTE-ACS. © 2016 Wiley Periodicals, Inc.

Abca1 deficiency protects the heart against myocardial infarction-induced injury

Background and aimsWe explored the role of ATP-binding cassette transporter A1 (Abca1), in post-myocardial infarction (MI) cardiac injury. MethodsIn Abca1–/– mice, wild type (WT) mice, and WT mice transplanted with Abca1–/– or WT bone marrow, an MI was induced in vivo. Furthermore, an ex vivo MI was induced in isolated Abca1–/– and WT hearts. ResultsTwenty-four hours and two weeks after in vivo MI induction, MI size was reduced in Abca1–/– (−58%, p = 0.007; −59%, p = 0.03) compared to WT. Ex vivo MI induction showed no effect of Abca1–/– on infarct size. Interestingly, two weeks after MI, Abca1–/– mice showed higher circulating levels of B-cells (+3.0 fold, p = 0.02) and T-cells (+4.2 fold, p = 0.002) compared to WT. Bone marrow-specific Abca1–/– tended to reduce infarct size (−43%, p = 0.12), suggesting a detrimental role for hematopoietic Abca1 after MI. ConclusionsAlthough Abca1 has a protective role in atherosclerosis, it exerts detrimental effects on cardiac function after MI.

The Probability of Inconstancy in Assessment of Cardiac Function Post-Myocardial Infarction in Mice.

In the present study, we explore the inherent variability that leads to overlaps in cardiac functional parameters between control and post-myocardial infarction (MI) mice. Heart failure was induced by Left Coronary Artery (LCA) ligation in mice. Average Ejection Fraction (EF) measured by echocardiography was lower in MI mice compared to control, but exhibited higher Standard Deviation (SD) and Standard Error (SEM), notably in 2D mode. Fractional Shortening (FS) showed a higher degree of overlap between MI and control mice even though the mean values were significantly different. Hemodynamic measurements of EF resulted in greater SD, SEM, ± 95% confidence intervals, and effect size. In comparing echocardiography at different time points, EF and FS were consistent by mean, but had apparent fluctuation in individual tracks, which were more obvious in MI than control mice. Hemodynamic measurements showed more complexity in data collection in mice in vivo. MI size showed variability that correlated with severity of cardiac function. These studies show that there is inherent variability in functional cardiac parameters after induction of heart failure by MI in mice. Analysis of these parameters by traditional statistical methods is insufficient, and we propose a more robust statistical analysis for proper data interpretation.

Abstract 11594: Reduction in Subtypes and Sizes of Myocardial Infarction With Ticagrelor in PEGASUS-TIMI 54

Objective: Ticagrelor reduced the risk of CV death, MI or stroke (MACE) in stable patients with prior MI in PEGASUS-TIMI 54. We investigated the efficacy of ticagrelor in reducing different subtypes and sizes of MI. Methods: MIs were adjudicated by the blinded TIMI Clinical Events Committee with definitions consistent with the Third Universal Definition of MI. Each MI was categorized by subtype and fold elevation of peak troponin (Tn) over the upper limit of normal (ULN). Results for both doses of ticagrelor were pooled in comparison to placebo. Results: A total of 1042 MIs occurred in the 21,162 randomized patients over a median follow up of 33 months. The majority (76%) of the MIs were spontaneous (Type 1), with demand MI (Type 2) and PCI-related (Type 4) accounting for 13% and 10% respectively (Figure Left); sudden death MI (Type 3) and CABG-related MI (Type 5) each accounted for &lt;1%. Using fold elevation in Tn, half of MIs (520, 50%) had a peak Tn ≥10x ULN and 21% of MIs (220) had a peak Tn ≥100x ULN (Figure Right). A total of 21% (224) were STEMI. Overall ticagrelor reduced MI at 3 yrs (4.47% vs 5.25%, HR 0.83, 95% CI 0.72 - 0.95, p=0.0055). The benefit was highly consistent among the different subtypes of MI (Figure left) and with increasing size of MI by fold elevation of Tn (Figure right) and for STEMI (HR 0.60, 95% CI 0.46 - 0.78, p=0.0002). Conclusion: In stable outpatients with a history of MI the majority of recurrent MI events are spontaneous and associated with a high biomarker elevation. Ticagrelor significantly reduces the incidence of MI consistently among different subtypes and biomarker sizes, with the greatest absolute reduction in spontaneous MIs, large MIs, and STEMI.

Abstract 17313: Multiparametric Cardiac MRI Documents Reduced LV Remodeling and Improved Contractile Function in Regions Adjacent to the Infarct After Pharmacologic Immunomodulation via Adenosine 2a Receptor Stimulation

Introduction: Agonists of the Adenosine 2a Receptor (A2aR) are used clinically as pharm-stress agents for perfusion imaging, but they are also potent immunomodulators that reduce the size of acute MI when administered at reperfusion in both large and small animal models of MI. Hypothesis: Sustained administration of an A2aR agonist can reduce post-MI LV remodeling and improve cardiac strain even when treatment is withheld until after infarct size has stabilized. Methods: Two groups of mice were studied: C57BL/6 mice treated with Vehicle or a highly selective A2aR agonist (ATL313). All mice received 1h coronary occlusion and 28d of reperfusion. ATL313 was administered for 28 days by subcutaneous micro-osmotic pumps implanted after MI. All mice underwent 7T CMR imaging at baseline and 2, 7 &amp; 28 days post-MI. CMR included short-axis black-blood cines covering the entire heart, with mid-ventricular cine DENSE for circumferential strain (Ecc). Late Gd-enhanced (LGE) inversion recovery imaging was performed on Days 2&amp;7 and molecular imaging with a collagen-targeted Gd contrast agent (EP3533) on Days 14&amp;28. Mice with Day 2 LGE infarct sizes less than 22% or &gt;42% LV mass were excluded from analysis. Results: Examples of LGE and DENSE analysis are shown in Panels A&amp;B. Day 2 infarct size was similar between groups (ATL313 (n=9): 35±2 vs Vehicle (n=8): 34±2, mean±SEM, p=NS). In panel C, ATL313 significantly improved LV end-systolic volume as early as 2 days post-MI (mean±SEM, *p&lt;0.05 vs Vehicle). In panel D, ATL313 improved Day 2 Ecc in adjacent zones vs. Vehicle (-10±2 vs -6±2%, *p&lt;0.05). In panel E, ATL313 reduced LV mass at Day 28 vs Vehicle (121±7 vs 143±7mg, *p&lt;0.05). Conclusions: Pharmacologic immunomodulation with an A2aR agonist inhibits LV remodeling, improves contractile function in infarct-adjacent regions at Day 2 post-MI and reduces LV mass at Day 28. Combined with previous work, these results suggest that A2aR stimulation may prove beneficial in both acute and sub-acute MI.

Clinicopathological significance of c-KIT mutation in gastrointestinal stromal tumors: a systematic review and meta-analysis.

Many types of KIT mutations have been observed in gastrointestinal stromal tumors (GISTs), but their prognostic and predictive significance are still unclear. A meta-analysis and literature review were conducted to estimate the contribution of KIT mutations in prognostic parameters and clinic-pathological significance of GISTs. A total of 18 relevant articles from PubMed, EMBASE and Web of Science databases were included in this study. The frequency of KIT mutation was significantly increased in the GIST patients with higher mitosis (≥5/50 high-power fields (HPFs) and larger size (≥5 cm) of tumors than in those with lower MI (≤5/50HPFs) and smaller size (≤5 cm) of GISTs respectively. The rate of KIT mutation was not significantly changed between GISTs in stomachs and in small intestines. KIT mutational status has prognostic significance for patients’ outcome. GIST patients with KIT exon 9 mutations have higher risk of progression than those with exon 11 mutations. 5 year relapse-free survival (RFS) rate was significantly higher in patients with KIT exon 11 deletion than in those with other type of KIT exon 11 mutations. The deletion involving KIT exon 11, particularly codons 557–558, is a valuable predictor of prognosis for patients with GISTs.

Abstract 259: Xenon-loaded Echogenic Liposomes Provide Cardioprotection in Acute Myocardial Infarction

Background: Acute myocardial infarction (AMI) is a leading cause of sudden cardiac death. Following AMI, left ventricular (LV) remodeling plays an important pathophysiologic role in progression to heart failure (HF). Effective therapeutic approaches to decrease the size of MI can reduce progression to HF. Xenon (Xe), a non-toxic, easily diffusible, noble gas can provide cardiovascular protection. However, delivery of Xe is challenging. Carrier delivery of Xe may be an effective way to deliver this gas to the ischemic area. We have developed Xe-loaded echogenic liposomes (Xe-ELIP) for intravascular delivery of the bioactive gas to the infarct area. Here, we investigate the effect of Xe-ELIP on MI size and LV remodeling in an AMI model. Methods: Xe-ELIP were prepared by a pressurization-freeze method. Rats were randomly divided into 4 groups; sham, AMI control, empty ELIP, and Xe-ELIP at 45 minutes following AMI. AMI was induced by ligating the left anterior descending artery. Liposomes were intravenously administrated immediately after reperfusion. Cardiac function was evaluated by ultrasound at baseline, after AMI, and on day 7. Infarct size was evaluated by TTC staining. Results: Gas chromatography-mass spectrometry demonstrated that 1 mg lipid contains 190 μl Xe. Xe-ELIP treatment decreased end-systolic LV volume (Fig. 1A), improved cardiac output, and reduced infract volume (Fig. 1B, 1C). Conclusion: This novel carrier system allows a therapeutic dose of Xe to reach the ischemic myocardium with resultant all preservation. This methodology can be easily translated for intracoronary injection of Xe-ELIP at the time of coronary intervention at AMI for cellular protection.

Status of Prostacycline-Thromboxane System and Platelet Functional Activities in Patients with Acute Myocardial Infarction Depending on Stages of Heart Failure

Among possible pathogenic and adaptive mechanism of acute myocardial infarction and development of its complications, the system of prostanoids, particularly prostacycline-thromboxane system is of prime importance. But many questions relating the role of prostacycline-thromboxane system in pathogenesis of myocardial infarction associated with heart failure have studied insufficiently. The objective of this work is to study the ststus of prostacycline-thromboxane system in patients of acute myocardial infarction associated with heart failure and its correlation with the platelet functions depending on stages of heart failure. This study was performed in the department of Internal Medicine in Kharkov State Medical Institute, Ukraine in 1985-89. 120 patients with acute myocardial infarction leading to heart failure were studied. The status of prostacycline-thromboxane was considered by the level of stable metabolites of prostacycline and thromboxane - A2 as 6-keto-PGF and TXB2 respectively in venous plasma. 6-Keto-PGF-1a and TXB2 levels were determined by Radio-immunological method with the help of kits manufactured by the English Firm "New England Nuclear". To determine the platelet aggregation properties, the instrument "Bian-120" transmitter was used. It was established clinically that prostacycline- thromboxane activation depends on clinical features of myocardial infarction, i.e. its localization, depth, extension or affected size of MI, first attack or re-infarction. Maximum changes of prostacycline thromboxane system took place in extensive myocardial infarction which was expressed in increased level of TXB2 and significant change of prostanoid imbalance ratio. Parameters of platelet aggregation function and prostacycline thromboxane system were interrelated during heart failure, which were expressed by their changes in aggregation diagram.Medicine Today 2014 Vol.26(2): 83-87

A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model.

AimThere is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction (AMI), for which the effectiveness of interventional reperfusion therapy is hampered by myocardial ischemia-reperfusion (IR) injury. Pretreatment with statins before ischemia is shown to reduce MI size in animals. However, no benefit was found in animals and patients with AMI when administered at the time of reperfusion, suggesting insufficient drug targeting into the IR myocardium. Here we tested the hypothesis that nanoparticle-mediated targeting of pitavastatin protects the heart from IR injury.Methods and ResultsIn a rat IR model, poly(lactic acid/glycolic acid) (PLGA) nanoparticle incorporating FITC accumulated in the IR myocardium through enhanced vascular permeability, and in CD11b-positive leukocytes in the IR myocardium and peripheral blood after intravenous treatment. Intravenous treatment with PLGA nanoparticle containing pitavastatin (Pitavastatin-NP, 1 mg/kg) at reperfusion reduced MI size after 24 hours and ameliorated left ventricular dysfunction 4-week after reperfusion; by contrast, pitavastatin alone (as high as 10 mg/kg) showed no therapeutic effects. The therapeutic effects of Pitavastatin-NP were blunted by a PI3K inhibitor wortmannin, but not by a mitochondrial permeability transition pore inhibitor cyclosporine A. Pitavastatin-NP induced phosphorylation of Akt and GSK3β, and inhibited inflammation and cardiomyocyte apoptosis in the IR myocardium.ConclusionsNanoparticle-mediated targeting of pitavastatin induced cardioprotection from IR injury by activation of PI3K/Akt pathway and inhibition of inflammation and cardiomyocyte death in this model. This strategy can be developed as an innovative cardioprotective modality that may advance currently unsatisfactory reperfusion therapy for AMI.

171 The genetic signature in ischaemic heart disease with myocardial infarction (MI) and significant left ventricular (LV) dysfunction

<h3></h3> The titingene (<i>TTN</i>) is a major determinant of myocardial function, its importance in both familial and ‘idiopathic’ Dilated Cardiomyopathy (DCM) has recently been ascertained. In some instances a second genetic mutation or a physiological perturbation (e.g. pregnancy) may reveal otherwise latent TTN mutation effects. We hypothesise that patients with pronounced LV dysfunction following MI, when controlling for infarct parameters and coronary anatomy, may have a high burden of <i>TTN </i>truncating variants (TTNtvs). We studied a large cohort of post-MI patients prospectively recruited at the Royal Brompton and Harefield NHS Foundation Trust. Gadolinium-enhanced Cardiac Magnetic Resonance was used to characterise cardiac dimensions, function and tissue properties. The size and thickness of MI, wall motion and number of hibernating segments were quantified by two experts blinded to genotype using a standard 17-segment model. Targeted re-sequencing of <i>TTN</i> and other key DCM genes was performed. Genetic variation in DCM genes in 530ethnically matchedhealthy volunteers along with public repositories was used for variant annotation and comparison. Our initial analyses show that out of the 336 post-MI patients, nine (2.7%) had a TTNtv. As hypothesised, TTNtv were significantly enriched in patients with LV ejection fraction (LVEF) &lt;35% (4.6% vs 1.4%, p = 0.01). Patients with a TTNtv had a significantly lower LVEF than those without (31.2 ± 13.9% vs 41.2 ± 14.7%; p = 0.026) Regression models taking into account cardiac, non-cardiac and genetic covariates are in process. These data identify a novel role of large effect size for <i>TTNtv</i>, in post-MI systolic dysfunction. Based on these findings it will be important to explore if genetic stratification of the post-MI patient can inform medical or revascularisation strategies.

Abstract 20665: Cardiac Arterial Spin Labeling MRI as a Novel Approach for in vivo Quantification of the Area-At-Risk

Introduction: T2-weighted cardiac magnetic resonance (CMR) imaging, which detects myocardial edema, has been used to retrospectively delineate the area-at-risk (AAR) in clinical cardioprotection studies. However, some of these cardioprotective interventions have been reported to reduce the extent of myocardial edema, thereby affecting the AAR delineated by T2-CMR. Here, we investigate arterial spin labelling (ASL)-CMR, which measures myocardial perfusion, as an alternative approach to measuring the AAR following acute ischemia-reperfusion injury (IRI). Methods: B6sv129 mice (10-14 weeks old) were subjected to an in vivo left main coronary artery ligation for 30 minutes followed by 72 hours reperfusion following which CMR was performed to determine MI size (late gadolinium enhancement) and the AAR (T2-mapping CMR and ASL CMR). These were then validated against MI size and the AAR measured by ‘gold-standard’ triphenyl tetrazolium chloride and Evan’s blue staining, respectively. Animals were subjected to a standard ischemic preconditioning (IPC) protocol comprising 5 minutes ischemia and reperfusion prior to the index ischemic insult. Results: T2-maps showed clearly defined regions of elevated T2-signal corresponding to the AAR delineated by histology (AAR/LV% in control: T2-CMR 60.4±2.4 versus histology 64.3±2.5:N=6/group;P&gt;0.05). However, in IPC-treated animals, the T2-maps significantly underestimated the AAR (AAR/LV% with IPC: T2-CMR 46.0±13.2 versus histology 59.8±7.8:N=10/group;P&lt;0.05). ASL-CMR also revealed clearly defined regions of attenuated ASL signal (indicated reduced myocardial blood flow) which appeared to correspond to the AAR delineated by histology (AAR/LV% in control: ASL-CMR 60.6±4.3 versus histology 64.3±3.9:N=6/group;P&gt;0.05). Crucially, the estimation of the AAR by ASL-CMR was not affected by IPC (AAR/LV% with IPC: ASL-CMR 53.4±7.9 versus histology 58.0±3.0:N=8/group;P&gt;0.05). Conclusions: We find that ASL-CMR has the potential to retrospectively delineate the AAR in the adult murine heart subjected to acute IRI in a similar manner to T2-mapping CMR. Crucially, unlike T2-mapping CMR however, the AAR delineated by ASL-CMR was not affected by the cardioprotective intervention, IPC.

THE ADULT MURINE HEART IS PROTECTED AGAINST ISCHEMIA-REPERFUSION INJURY IN THE ABSENCE OF BOTH MITOFUSIN (MFN) PROTEINS

BackgroundCardiac-specific ablation of both Mfn1 and Mfn2 in the adult heart results in mitochondrial fragmentation and a lethal cardiomyopathy after about 6 weeks. The effect of combined Mfn1 and Mfn2...

Imaging of cardiac and renal perfusion in a rat model with 13N-NH 3 micro-PET.

Cardiac dysfunction leads to decreased organ perfusion. We aimed to measure cardiac and renal perfusion simultaneously with the use of (13)N-NH3-microPET in different rat models. Ten male Wistar rats underwent sham surgery (n=5) or permanent coronary artery ligation to induce myocardial infarction (MI, n=5). Eleven weeks later (13)N-NH3-microPET scan was performed to study the cardiac and renal perfusion. Cardiac perfusion was significantly reduced in MI group, directly correlated with ejection fraction and inversely correlated with MI size (r=0.89; p<0.001 and r=-0.86; p<0.001 respectively). Renal perfusion showed a notional 17% non-significant reduction in MI group when compared to sham (3.44±0.40 vs. 4.12±0.48ml/g/min). There was a trend towards greater reduction of perfusion in cortical than medullar region. Cortex perfusion was negatively correlated with histological changes. (13)N-NH3-microPET may be a potential tool for evaluation of cardiac and renal functional and perfusion changes in presence of cardiac dysfunction in rat models.

CMRSegTools: an Osirix plugin for myocardial infarct sizing on DE-CMR images

Background CMR is an established method for the diagnosis and assessment of myocardial infarction in routine exams. In addition, there has been a growing interest in using infarct size as a surrogate endpoint for clinical trials assessing the efficacy of acute MI reperfusion treatments and MI size is reported to be a stronger predictor of outcome than LVEF and LV volumes[1].Various methods have been proposed for infarct size (IS) measurement without reference standard method and side-by-side comparison among them. The goal was to develop a user-friendly cardiac segmentation toolbox implemented as a plugin in the open-source OsiriX software with a set a commonly proposed semi-automatic algorithms

Transcriptional profiling of left ventricle and peripheral blood mononuclear cells in a rat model of postinfarction heart failure

BackgroundMyocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. The aim of this study was to investigate gene expression in the LV and to evaluate their reflection in peripheral blood mononuclear cells (PBMCs).MethodsMI was induced in rats by ligation of the proximal left coronary artery. Rats with small, moderate, and large MI size were included into the experiment two months after the operation. The development of heart failure was estimated by echocardiography and catheterization. Microarrays were used to compare the LV and PBMCs transcriptomes of control and experimental animals.ResultsOnly rats with a large MI developed extensive LV remodeling and heart failure. 840 transcripts were altered in LV of failing hearts, and especially numerous were those associated with the extracellular matrix. In contrast, no significant gene expression changes were seen in LVs of rats with moderate or small MI that had compensated LV injury. We showed that ceruloplasmin was similarly overexpressed in the heart and blood in response to HF, whereas downregulation of tetraspanin 12 was significant only in the PBMCs.ConclusionA large size of infarcted area is critical for progression of LV remodeling and HF development, associated with altered gene expression in the heart. Ceruloplasmin and tetraspanin 12 are potential convenient markers in readily obtainable PBMCs.

GW24-e1190 The Therapeutic Potential of Gene Modified by Adeno-Associated Virus Combined with PDGF-BB in MI

ObjectivesTo explore the feasibility, safety, and anti-apoptosis effect and to investigate the therapeutic potential of gene modified by adeno-associated virus combined with PDGF-BB in MI.MethodsThe neonatal cardiomyocytes were isolated, cultured,...