Background/Objectives: This study aimed to compare changes in functional and strain parameters in young and old mice using cardiac MRI before and shortly after myocardial infarction. Methods: In this prospective experimental study, 7 young mice and 10 old mice underwent a cardiac MRI 5 days before and 2 days after myocardial infarction by LAD ligation. Functional parameters such as EDV, ESV, EF, SV, and Strain were determined. Results: EDV in the young mice before LAD ligation was significantly lower than in the old mice (p-value 0.002). EDV significantly increased after infarction in both groups. ESV was significantly lower in young mice before infarction than in old mice (9.7 ± 2.6 vs. 13.8 ± 3.9 [µL], p = 0.029). After infarction, the mean value was still lower but no longer significant. There was no significant difference between young and old mice either before or after infarction for the EF. But again, the decrease was significant for both groups (old: p < 0.0001 and young: p = 0.0009). Each global strain showed deterioration after infarction. This difference was significant in both subgroups for young mice and old mice for each strain. There were no differences either before or after infarction between the young and old mice. Conclusions: There were differences in functional parameters between young and old mice in EDV, SV, and CO. Changes in strain parameters in the acute phase post-myocardial infarction did not differ significantly between young and old mice, while there was a clear deterioration in strain parameters after infarction in both groups.

Angiogenesis is crucial in myocardial healing after myocardial infarction (MI). The αvβ3-integrin, a key regulator of angiogenesis, is targeted by RGD-based PET tracers like [68Ga]Ga-NODAGA-RGD. Yet, angiogenesis imaging using RGD-based tracers is seriously hampered by the lack of true specificity of the αvβ3-integrin for angiogenic cells. Therefore, our study aimed to identify the cell type with the highest αvβ3-integrin expression in the process of myocardial healing in order to determine the actual value of the PET tracer [68Ga]Ga-NODAGA-RGD for imaging post-MI angiogenesis. Cardiac magnetic resonance imaging (CMR) was used to assess cardiac function and morphology after 28 days in two groups: permanent ligation (PL) of the left anterior descending coronary artery and transient occlusion for 30 min (I/R). Following these measurements, hearts were excised for histological and immunohistological examinations to evaluate scar formation, capillary density, and cellular composition. PET imaging with [68Ga]Ga-NODAGA-RGD was conducted on day 5 and day 7 post-MI. Single-nucleus transcriptomics were performed to identify cell clusters expressing αvβ3-integrin. Both infarct models induced scar formation, with the PL group developing large infarcts accompanied by massive left ventricular dilation and hypertrophy of cardiomyocytes, while the I/R group exhibited small intramural scars without significant changes in LV geometry or function. PET imaging revealed significantly higher tracer accumulation in the infarct area of the PL group compared to the I/R group. Single-nucleus transcriptomics performed 5 days post-MI revealed that angiogenesis markers were enriched in the I/R group, while the highest αvβ3-integrin mRNA expression was identified in the fibroblast cluster, indicating an activated phenotype. Activated fibroblasts are the primary target cells of [68Ga]Ga-NODAGA-RGD, rather than angiogenic cells. In this regard, [68Ga]Ga-NODAGA-RGD is most probably not a valid tracer for imaging angiogenesis during the first days post-MI.

Background The initial idea of functional tissue replacement has shifted to the concept that injected cells positively modulate myocardial healing by a non-specific immune response of the transplanted cells within the target tissue. This alleged local modification of the scar requires assessment of regional properties of the left ventricular wall in addition to commonly applied measures of global morphological and functional parameters. Hence, we aimed at investigating the effect of cardiac cell therapy with cardiovascular progenitor cells, so-called cardiac induced cells, on both global and regional properties of the left ventricle by a multimodal imaging approach in a mouse model. Methods Myocardial infarction was induced in mice by ligation of the left anterior descending artery, the therapy group received an intramyocardial injection of 1 × 10 6 cardiac induced cells suspended in matrigel, the control group received matrigel only. [ 18 F]FDG positron emission tomography imaging was performed after 17 days, to assess regional glucose metabolism. Three weeks after myocardial infarction, cardiac magnetic resonance imaging was performed for morphological and functional assessment of the left ventricle. Following these measurements, hearts were excised for histological examinations. Results Cell therapy had no significant effect on global morphological parameters. Similarly, there was no difference in scar size and capillary density between therapy and control group. However, there was a significant improvement in contractile function of the left ventricle – left ventricular ejection fraction, stroke volume and cardiac output. Regional analysis of the left ventricle identified changes of wall properties in the scar area as the putative mechanism. Cell therapy reduced the thinning of the scar and significantly improved its radial contractility. Furthermore, the metabolic defect, assessed by [ 18 F]FDG, was significantly reduced by the cell therapy. Conclusion Our data support the relevance of extending the assessment of global left ventricular parameters by a structured regional wall analysis for the evaluation of therapies targeting at modulation of healing myocardium. This approach will enable a deeper understanding of mechanisms underlying the effect of experimental regenerative therapies, thus paving the way for a successful translation into clinical application.

Novel therapeutic strategies aiming at improving the healing process after an acute myocardial infarction are currently under intense investigation. The mouse model plays a central role for deciphering the underlying mechanisms on a molecular and cellular level. Therefore, we intended to assess in-vivo post-infarct remodeling as comprehensively as possible using an expedient native magnetic resonance imaging (MRI) in the two most prominent infarct models, permanent ligation (PL) of the left anterior descending artery (LAD) versus ischemia reperfusion (I/R). Mice were subjected to either permanent or transient (45 min) occlusion of the LAD. After 3 weeks, examinations were performed with a 7-Tesla small animal MRI system. Data analysis was performed with the freely available software Segment. PL resulted in a massive dilation of the left ventricle, accompanied by hypertrophy of the non-infarcted myocardium and a decline of contractile function. These effects were less pronounced following I/R compared to healthy animals. Single plane assessments were not sufficient to capture the specific differences of left ventricular (LV) properties between the two infarct models. Bulls-eye plots were found to be an ideal tool for qualitative LV wall assessment, whereas a multi-slice sector-based analysis of wall regions is ideal to determine differences in hypertrophy, lateral wall thinning and wall thickening on a quantitative level. We combine the use of polar map-based analysis of LV wall properties with volumetric measurements using simple CINE CMR imaging. Our strategy represents a versatile and easily available tool for serial assessment of the LV during the remodeling process. Our study contributes to a better understanding of the effects of novel therapies targeting the healing of damaged myocardium.

Main problems of the tissue engineering of complex tissue constructs are based on the limited possibilities to arrange cells in a three dimensional matrix with a high grade of purity of the respective cell type and the insufficient nutrition of the cells after implantation. Aim of the here presented study was to engineer three dimensional tissue constructs with the help of laser-induced forward transfer (LIFT). For this purpose cultivated skin cell lines (keratinocytes, fibroblasts) and human mesenchymal stem cells (MSC) have been transferred by LIFT and have been evaluated for immediate survival, viability, apoptosis and DNA damage. Furthermore MSC have been analyzed by flow cytometry for potential induction of differentiation after LIFT.

Various studies demonstrate erythropoietin (EPO) as a cardioprotective growth hormone. Recent findings reveal EPO in addition might induce proliferation cascades inside myocardium. We aimed to evaluate whether a single high-dose intramyocardial EPO administration safely elevates early intracardiac cell proliferation after myocardial infarction (MI). Following permanent MI in rats EPO (3000 U/kg) in MI EPO-treatment group (n=99) or saline in MI control group (n=95) was injected along the infarction border. Intramyocardial EPO injection activated the genes of cyclin D1 and cell division cycle 2 kinase (cdc2) at 24 h after MI (n=6, P<0.05) evaluated by real time-PCR. The number of Ki-67+ intracardiac cells analyzed following immunohistochemistry was significantly enhanced by 45% in the peri-infarction zone at 48 h after EPO treatment (n=6, P<0.001). Capillary density was significantly enhanced by 17% as early as seven days (n=6, P<0.001). After six weeks, left ventricular performance assessed by conductance catheters was restored under baseline and dobutamine induced stress conditions (n=11-14, P<0.05). No thrombus formation was observed in the heart and in distant organs. No deleterious systemic adverse effects were apparent. Single high-dose intramyocardial EPO delivery proved safety and promoted early intracardiac cell proliferation, which might in part have contributed to an attenuated myocardial functional decline.