The goals of the thesis were to, in pig models, (1) assess manganese-enhanced magnetic resonance imaging (MEMRI) in the characterization of acute and chronic ischemia-induced myocardial infarction (MI), (2) characterize cryoinjury-induced MI with contrast-enhanced MRI and optical methods, and (3) observe the effects of locally released angiogenic factors on the repair of cryoinjury-induced MI. Firstly, after acute MI was established by occlusion of the coronary artery branches, the pig hearts were isolated and mounted onto an ex vivo perfusion system inside a 7T magnet. After administration of MnCl2, T1-weighted MR images showed gradual enhancement of signal intensity within the normal myocardium, whereas the ischemic counterpart remained hypointense. During chronic MI progression, the intensity increased slowly after exposure to MnCl2 within the infarcted myocardium. Secondly, a new MI model was tested via direct 2-min contact of left ventricular epicardium with a liquid nitrogen-cooled aluminum bar. Subsequent in vivo Gd-enhanced MRI showed a uniform hypointense area (~10 mm in depth) surrounded by a hyperintense rim. Histology showed erythrocytes embolism within the cryolesion with a thin necrotic rim neighboring the normal myocardium. Four weeks later, the cryoinjured myocardium was replaced by scar tissue. Thirdly, in vivo MEMRI was tested on this cryoinjury model. After intravenous administration of MnCl2 via intermittent bolus or continuous infusion, normal myocardium showed prolonged hyperintense, which led to significant signal contrast between it and cryoinjured myocardium. Continuous infusion scheme minimized hemodynamic fluctuation. Finally, angiogenic therapy was assessed by anchoring of vascular growth factors-loaded alginate beads or adipose-derived stem cells (ADSCs)-loaded agarose patch on top of the cryoinjured myocardium. Gd-enhanced MRI revealed (1) growth of new tissue wrapping the growth factors-loaded alginate beads and (2) higher perfusion within the ADSCs-treated cryoinjured myocardium as compared with the growth factors-treated counterpart. Histological and fluorescent microsphere examination revealed that ADSCs induced more significant growth of mature microvasculature within the cryoinjured myocardium. These results indicate that MnCl2 could characterize MI ex vivo and in vivo. Epicardial implantation of ADSCs-loaded agarose hydrogel can induce angiogenesis within the cryoinjured myocardium, a form of MI with similar progression features as that induced by ischemia.

The goals of the thesis were to, in pig models, (1) assess manganese-enhanced magnetic resonance imaging (MEMRI) in the characterization of acute and chronic ischemia-induced myocardial infarction (MI), (2) characterize cryoinjury-induced MI with contrast-enhanced MRI and optical methods, and (3) observe the effects of locally released angiogenic factors on the repair of cryoinjury-induced MI. Firstly, after acute MI was established by occlusion of the coronary artery branches, the pig hearts were isolated and mounted onto an ex vivo perfusion system inside a 7T magnet. After administration of MnCl2, T1-weighted MR images showed gradual enhancement of signal intensity within the normal myocardium, whereas the ischemic counterpart remained hypointense. During chronic MI progression, the intensity increased slowly after exposure to MnCl2 within the infarcted myocardium. Secondly, a new MI model was tested via direct 2-min contact of left ventricular epicardium with a liquid nitrogen-cooled aluminum bar. Subsequent in vivo Gd-enhanced MRI showed a uniform hypointense area (~10 mm in depth) surrounded by a hyperintense rim. Histology showed erythrocytes embolism within the cryolesion with a thin necrotic rim neighboring the normal myocardium. Four weeks later, the cryoinjured myocardium was replaced by scar tissue. Thirdly, in vivo MEMRI was tested on this cryoinjury model. After intravenous administration of MnCl2 via intermittent bolus or continuous infusion, normal myocardium showed prolonged hyperintense, which led to significant signal contrast between it and cryoinjured myocardium. Continuous infusion scheme minimized hemodynamic fluctuation. Finally, angiogenic therapy was assessed by anchoring of vascular growth factors-loaded alginate beads or adipose-derived stem cells (ADSCs)-loaded agarose patch on top of the cryoinjured myocardium. Gd-enhanced MRI revealed (1) growth of new tissue wrapping the growth factors-loaded alginate beads and (2) higher perfusion within the ADSCs-treated cryoinjured myocardium as compared with the growth factors-treated counterpart. Histological and fluorescent microsphere examination revealed that ADSCs induced more significant growth of mature microvasculature within the cryoinjured myocardium. These results indicate that MnCl2 could characterize MI ex vivo and in vivo. Epicardial implantation of ADSCs-loaded agarose hydrogel can induce angiogenesis within the cryoinjured myocardium, a form of MI with similar progression features as that induced by ischemia.