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This study investigates the cardioprotective effects of Paeoniflorin (PF) on left ventricular remodeling following acute myocardial infarction (AMI) under conditions of hypobaric hypoxia. Left ventricular remodeling post-AMI plays a pivotal role in exacerbating heart failure, especially at high altitudes. Using a rat model of AMI, the study aimed to evaluate the cardioprotective potential of PF under hypobaric hypoxia. Ninety male rats were divided into four groups: sham-operated controls under normoxia/hypobaria, an AMI model group, and a PF treatment group. PF was administered for 4 weeks after AMI induction. Left ventricular function was assessed using cardiac magnetic resonance imaging. Biochemical assays of cuproptosis, oxidative stress, apoptosis, inflammation, and fibrosis were performed. Results demonstrated PF significantly improved left ventricular function and remodeling after AMI under hypobaric hypoxia. Mechanistically, PF decreased FDX1/DLAT expression and serum copper while increasing pyruvate. It also attenuated apoptosis, inflammation, and fibrosis by modulating Bcl-2, Bax, NLRP3, and oxidative stress markers. Thus, PF exhibits therapeutic potential for left ventricular remodeling post-AMI at high altitude by inhibiting cuproptosis, inflammation, apoptosis and fibrosis. Further studies are warranted to optimize dosage and duration and elucidate PF's mechanisms of action., (© 2024. The Author(s).)

Background: The actual role of the coronary microcirculation, which is massively injured by myocardial infarction (MI), in intramyocardial hemorrhage (IMH) pathophysiology is still not fully understood., Purpose: To determine the change and distribution of microcirculation of myocardial edema (ME), IMH, MI, and the remote area of early reperfusion using 7.0-T cardiovascular magnetic resonance (CMR) in a rat model of acute MI., Material and Methods: Eight rats with 60-min myocardial ischemia followed by reperfusion were investigated. On days 2 and 7, after the acquisition of T2*-mapping and T2-mapping images, late gadolinium enhancement imaging was performed to evaluate the extent of myocardial ischemia after an injection of Gd-DTPA. On days 3 and 8, after the injection of ultrasmall superparamagnetic iron oxide (USPIO), T2*- and T2-mapping images were acquired. The R2 values of ME, IMH, MI, and remote areas were measured., Results: From days 2 to 3, R2 values increased in the IMH, MI, ME, and remote area (all P  < 0.05) following administration of USPIO, while the delta R2 value of IMH and MI was larger than remote area ( P  < 0.05). From day 7 to day 8, there was no significant difference in the IMH, MI, ME, and remote area (all P  > 0.05)., Conclusion: Microvascular injury of IMH and MI is the most severe among all the studied myocardial injuries in the early reperfusion of MI, while microvascular density decreased during follow-up.

Background: In previous studies, haemorrhage occurred only with large infarct sizes, and studies found a moderate correlation between the extent of necrosis and haemorrhage, but the extent of infarction size in these studies was limited. This study aimed to find the correlations between intramyocardial haemorrhage (IMH), myocardial infarction (MI), and myocardial oedema (ME) from small to large sizes of MI in a 7.0-T MR scanner., Methods: Different sizes of myocardial infarction were induced by occluding different sections of the proximal left anterior descending coronary artery (1-3 mm under the left auricle). T2*-mapping, T2-mapping and late gadolinium enhancement (LGE) sequences were performed on a 7.0 T MR system at Days 2 and 7. T2*- and T2-maps were calculated using custom-made software. All areas were expressed as a percentage of the entire myocardial tissue of the left ventricle. The rats were divided into two groups based on the T2* results and pathological findings; MI with IMH was referred to as the + IMH group, while MI without IMH was referred to as the -IMH group., Results: The final experimental sample consisted of 25 rats in the + IMH group and 10 rats in the -IMH group. For the + IMH group on Day 2, there was a significant positive correlation between IMH size and MI size (r = 0.677, P < 0.01) and a positive correlation between IMH size and ME size (r = 0.552, P < 0.01). On Day 7, there was a significant positive correlation between IMH size and MI size (r = 0.711, P < 0.01), while no correlation was found between IMH size and ME size (r = 0.429, P = 0.097). The MI sizes of the + IMH group were larger than those of the -IMH group (P < 0.01)., Conclusions: Infarction size prior to reperfusion is a critical factor in determining IMH size in rats., (© 2022. The Author(s).)

Background: This study investigates the segmental myocardial strain of the early phase of intramyocardial hemorrhage (IMH) caused by reperfused myocardial infarction (MI) in rats by low-dose dobutamine (LDD) cardiovascular magnetic resonance (CMR) feature-tracking., Methods: Nine sham rats and nine rats with 60-min myocardial ischemia followed by 48-h reperfusion were investigated using CMR, including T2*-mapping sequence and fast imaging with steady-state precession (FISP)-cine sequence. Another FISP-cine sequence was acquired after 2 min of dobutamine injection; the MI, IMH, and Non-MI (NMI) areas were identified. The values of peak radial strains (PRS) and peak circumferential strains (PCS) of the MI, IMH and NMI segments were acquired. The efficiency of PRS and PCS (EPRS and EPCS, respectively) were calculated on the basis of the time of every single heartbeat., Results: The PRS, PCS, EPRS, and EPCS of the sham group increased after LDD injection. However, the PRS, PCS, EPRS, and EPCS of the IMH segment did not increase. Moreover, the PRS and PCS of the MI and NMI segments did not increase, but the EPRS and EPCS of these segments increased. The PRS, PCS, EPRS, and EPCS of the IMH segment were lower than those of the MI and NMI segments before and after LDD injection, but without a significant difference between MI segment and NMI segment before and after LDD injection., Conclusions: LDD could help assess dysfunctions in segments with IMH, especially using the efficiency of strain. IMH was a crucial factor that decreased segmental movement and reserved function., (© 2021. The Author(s).)

Objective: A failed electrocardiography (ECG)-trigger often leads to a long acquisition time (TA) and deterioration in image quality. The purpose of this study was to evaluate and optimize the technique of self-gated (SG) cardiovascular magnetic resonance (CMR) for cardiac late gadolinium enhancement (LGE) imaging of rats with myocardial infarction/reperfusion., Materials and Methods: Cardiovascular magnetic resonance images of 10 rats were obtained using SG-LGE or ECG with respiration double-gating (ECG-RESP-gating) method at 7T to compare differences in image interference and TA between the two methods. A variety of flip angles (FA: 10°-80°) and the number of repetitions (NR: 40, 80, 150, and 300) were investigated to determine optimal scan parameters of SG-LGE technique based on image quality score and contrast-to-noise ratio (CNR)., Results: Self-gated late gadolinium enhancement allowed successful scan in 10 (100%) rats. However, only 4 (40%) rats were successfully scanned with the ECG-RESP-gating method. TAs with SG-LGE varied depending on NR used (TA: 41, 82, 154, and 307 seconds, corresponding to NR of 40, 80, 150, and 300, respectively). For the ECG-RESP-gating method, the average TA was 220 seconds. For SG-LGE images, CNR (42.5 ± 5.5, 43.5 ± 7.5, 54 ± 9, 59.5 ± 8.5, 56 ± 13, 54 ± 8, and 41 ± 9) and image quality score (1.85 ± 0.75, 2.20 ± 0.83, 2.85 ± 0.37, 3.85 ± 0.52, 2.8 ± 0.51, 2.45 ± 0.76, and 1.95 ± 0.60) were achieved with different FAs (10°, 15°, 20°, 25°, 30°, 35°, and 40°, respectively). Optimal FAs of 20°-30° and NR of 80 were recommended., Conclusion: Self-gated technique can improve image quality of LGE without irregular ECG or respiration gating. Therefore, SG-LGE can be used an alternative method of ECG-RESP-gating.

Objective: To understand microstructural changes after myocardial infarction (MI), we evaluated myocardial fibers of rhesus monkeys during acute or chronic MI, and identified the differences of myocardial fibers between acute and chronic MI., Materials and Methods: Six fixed hearts of rhesus monkeys with left anterior descending coronary artery ligation for 1 hour or 84 days were scanned by diffusion tensor magnetic resonance imaging (MRI) to measure apparent diffusion coefficient (ADC), fractional anisotropy (FA) and helix angle (HA)., Results: Comparing with acute MI monkeys (FA: 0.59 ± 0.02; ADC: 5.0 ± 0.6 × 10(-4) mm(2)/s; HA: 94.5 ± 4.4°), chronic MI monkeys showed remarkably decreased FA value (0.26 ± 0.03), increased ADC value (7.8 ± 0.8 × 10(-4)mm(2)/s), decreased HA transmural range (49.5 ± 4.6°) and serious defects on endocardium in infarcted regions. The HA in infarcted regions shifted to more components of negative left-handed helix in chronic MI monkeys (-38.3 ± 5.0°-11.2 ± 4.3°) than in acute MI monkeys (-41.4 ± 5.1°-53.1 ± 3.7°), but the HA in remote regions shifted to more components of positive right-handed helix in chronic MI monkeys (-43.8 ± 2.7°-66.5 ± 4.9°) than in acute MI monkeys (-59.5 ± 3.4°-64.9 ± 4.3°)., Conclusion: Diffusion tensor MRI method helps to quantify differences of mechanical microstructure and water diffusion of myocardial fibers between acute and chronic MI monkey's models.

Background: The common T2 mapping is not suitable for the use in rat heart with high heart rate, unless data are acquired in multiple cardiac cycles., Purpose: To evaluate a simplified T2 mapping method for faster assessment of myocardial edema and area at risk in a rat model of myocardial infarction., Material and Methods: The simplified T2 mapping method (TR/TE, 1500 ms/10, 20, 30 ms) was implemented at a 7.0T MRI system. The accuracy of T2 mapping was compared with a standard T2 mapping method (TR, 2500 ms, 16 TEs equally spaced from 11 ms to 176 ms) in thigh muscles in rats (n = 6) and a phantom. This method was further evaluated in normal rats (n = 8) and rats with myocardial infarction (n = 8). Late gadolinium enhancement images were also acquired in the rats with myocardial infarction., Results: T2 values of simplified T2 mapping in the muscles and phantom were 27.3 ± 2 ms and 26.5 ± 1.1 ms, which were similar to the T2 values obtained by the standard T2 mapping method (28.1 ± 1.4 ms, P > 0.05; 26.9 ± 1.7 ms). No significant difference in T2 distribution (different segments and slices from base to apex) in the whole heart was found in normal rats (25.6 ± 3.3 ms, P > 0.05). The mean T2 value in the myocardial edema regions of myocardial infarction rats (37 ± 4.9 ms) was significantly higher than that of the normal rats (25.6 ± 3.3 ms, P < 0.001). The T2 value in the myocardial infarction core of myocardial infarction rats (39.9 ± 3.6 ms) was significantly higher than that of area at risk (34.7 ± 2.9 ms, P < 0.001)., Conclusion: The simplified myocardial T2 mapping is technically feasible and accurate, and can readily detect myocardial edema and area at risk in rats with high heart rate., (© The Foundation Acta Radiologica 2014.)

Rationale and Objectives: Firefly luciferase (Fluc) reporter gene is an authentic marker for surviving stem cells. However, it is unable to visualize the intramyocardial delivery of stem cells or their impact on cardiac function. The investigators demonstrate that bioluminescence imaging (BLI) combined with magnetic resonance imaging (MRI) allows better assessment of cell delivery and the impact on post-myocardial infarction remodeling., Materials and Methods: Murine embryonic stem cells (0.3 million) were double-labeled with Fluc and superparamagnetic iron oxide particles and injected into the infarct border zone of athymic rat hearts. BLI and MRI were performed serially up to 2 months after injection, followed by immunohistochemistry., Results: Dual-modality imaging was able to verify the initial intramyocardial delivery of the cells and their survival status. Over time, BLI signal increased in seven of nine hearts and disappeared in the other two hearts. The divergence of BLI signal over time was supported by MRI findings. Left ventricular ejection fraction and fractional shortening estimated by MRI suggested that cell engraftment mediated a positive impact on post-myocardial infarction remodeling. Two months after intramyocardial injection, superparamagnetic iron oxide-associated signals facilitated the localization of the injection site., Conclusions: Dual-modality imaging has the unique ability to monitor cell delivery, survival status, graft morphology, and impact on post-myocardial infarction remodeling., (Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.)

Purpose: To use magnetic resonance (MR) imaging and positron emission tomography (PET) dual detection of cardiac-grafted embryonic stem cells (ESCs) to examine (a) survival and proliferation of ESCs in normal and infarcted myocardium, (b) host macrophage versus grafted ESC contribution to serial MR imaging signal over time, and (c) cardiac function associated with the formation of grafts and whether improvement in cardiac function is related to cardiac differentiation of ESCs., Materials and Methods: All animal procedures were approved by the institutional animal care and use committee. Murine ESCs were stably transfected with a mutant version of herpes simplex virus type 1 thymidine kinase, HSV1-sr39tk, and also were labeled with superparamagnetic iron oxide (SPIO) particles. Cells were injected directly in the border zone of the infarcted heart or in corresponding regions of normal hearts in athymic rats. PET and MR imaging were performed longitudinally for 4 weeks in the same animals., Results: ESCs survived and underwent proliferation in the infarcted and normal hearts, as demonstrated by serial increases in 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl) guanine PET signals. In parallel, the hypointense areas on MR images at the injection sites decreased over time. Double staining for host macrophages and SPIO particles revealed that the majority of SPIO-containing cells were macrophages at week 4 after injection. Left ventricular ejection fraction increased in the ESC-treated rats but decreased in culture media-treated rats, and border-zone function was preserved in ESC-treated animals; however, cardiac differentiation of ESCs was less than 0.5%., Conclusion: Dual-modality imaging permits complementary information in regard to cell survival and proliferation, graft formation, and effects on cardiac function., Supplemental Material: http://radiology.rsnajnls.org/cgi/content/full/250/3/821/DC1., (RSNA, 2009)

Purpose: To investigate T2 mapping at 7T magnetic resonance imaging (MRI) for the detection and quantification of reperfused intramyocardial hemorrhage (IMH) in a rat model.Materials and Methods: Myocardial infarction (MI) was induced in 25 female rats. Rats were scanned at a 7T MRI 48 hours after reperfusion, using T2 mapping and late gadolinium enhancement imaging. Gross sections of the left ventricular myocardium and corresponding hematoxylin and eosin staining were assessed for IMH. T2 mapping images were matched with the gross sections. The IMH volume, expressed as a percentage of the left ventricular myocardial volume, of each heart determined by T2 mapping was compared with that calculated by pathological gross examination.Results: Six rats died. In all, 97 gross sections of the left ventricular myocardium from the 19 rats were matched with T2 mapping images. IMH occurred pathologically in 68 gross sections, which was detected as hypointense cores by T2 mapping in 63 images (93% sensitivity). Three T2 mapping images with hypointense cores showed no hemorrhage on pathological sections (90% specificity). The positive and negative predictive values of hemorrhage on T2 mapping were 95% and 84%, respectively. In terms of the IMH volume, there was no significant difference between T2 mapping and pathological gross measurements (4.8 ± 2.4% vs. 5.3 ± 3.2%; P = 0.11).Conclusion: T2 mapping at 7T MRI can reliably detect and quantify IMH in rats in vivo. This may be useful as a noninvasive quantitative approach to investigating the mechanisms and evolution of MI and reperfusion injury. J. Magn. Reson. Imaging 2016;44:194-203. [ABSTRACT FROM AUTHOR]