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In this pilot study, we compared the infarct and edema size in acute myocardial infarction (MI) patients treated by nicorandil with those treated by nitrate, using cardiac magnetic resonance (CMR) imaging. Fifty-two acute MI patients who underwent emergency percutaneous coronary intervention (PCI) were enrolled, and were assigned to receive nicorandil or nitrate at random just before reperfusion. For the assessment of infarct and edema areas, short-axis delayed enhancement (DE) and T2-weight (T2w) CMR images were acquired 6.1 ± 2.4 days after the onset of MI. A significant correlation was observed between the peak creatinine kinase (CK) level and the infarct size on DE CMR (r = 0.62, p

Objective— Light-type caldesmon ( l -CaD) is a potent cytostatic and antiangiogenic protein that regulates cell growth and survival via modulation of the cell shape and cytoskeleton. The aim of this study is to explore the potential value of l -CaD for use as a cytostatic agent to inhibit neointimal formation after angioplasty by suppressing vascular smooth muscle cell (VSMC) growth and migration. Methods and Results— We tested the cytostatic function of l -CaD in cultured VSMCs using assays for apoptosis, cell proliferation, and migration, and evaluated the expression pattern of relevant signaling proteins (focal adhesion kinase [FAK] and mitogen-activated protein kinases) in VSMCs. Transfection of adenoviral vector encoding l -CaD (Ad- l -CaD) resulted in progressive loss of actin stress fibers and cell retraction. Enzyme-linked immunosorbent assay demonstrated that Ad- l -CaD transfection increased the apoptosis rate by 75% and reduced BrdU uptake by 49%. Furthermore, transfection of Ad- l -CaD inhibited migration of VSMCs induced by platelet-derived growth factor-BB (PDGF) by 36% ( P l -CaD overexpression reduced PDGF-induced phosphorylation of both FAK and extracellular signal regulated-kinase (ERK). In balloon-injured rat carotid arteries, Ad- l -CaD transfection inhibited neointimal formation by 37% ( P Conclusions— Overexpression of l -CaD suppressed cell growth and survival in VSMCs and inhibited neointimal formation after experimental angioplasty, partly by regulating the cytoskeletal tension-FAK-ERK axis.

Cardiogenic shock developed in a 72-year-old Japanese woman during combination therapy with verapamil and atenolol for recurrent supraventricular arrhythmia. She had coronary atherosclerosis, liver cirrhosis and brady-cardia-tachycardia syndrome. Despite of the high-dose catecholamines and counterpulsation, she progressively deteriorated. Bolus administration of intravenous calcium chloride (CaCl2) immediately resolved her hemodynamic collapse.

To differentiate acute from chronic damage to the myocardium in patients with myocardial infarction (MI) using DE and T2w MR. Short-axis T2w and DE MR images were acquired twice after the onset of MI in 36 patients who successfully underwent emergency coronary revascularisation. The areas of infarct and oedema were measured. The oedema-infarct ratio (O/I) of the left ventricular area was calculated by dividing the oedema by the infarct area. The oedema size on T2w MR was significantly larger than the infarct size on DE MR in the acute phase. Both the oedema size on T2w MR and the infarct size on DE MR in the acute phase were significantly larger than those in the chronic phase. The O/I was significantly greater in the acute phase compared with that in the chronic phase (P

Background— Circulating endothelial progenitor cells (EPCs) are known to be involved in vasculogenesis and mobilized after acute myocardial infarction (AMI). To test the hypothesis that the angiogenic function of EPCs affects post-myocardial infarction (MI) myocardial salvage, we evaluated the number and potential differentiation of EPCs and compared these data with clinical parameters 6 months after MI. Methods and Results— Consecutive 51 patients (age, 61±8 years, mean±SD) with primary AMI who were successfully treated with stenting were enrolled. EPC identified as CD45 low , CD34 + , CD133 + , and VEGFR2 + was quantified by a flow cytometry. The potential of EPCs to differentiate into endothelial cells (EPC differentiation) was also confirmed by the upregulation of CD31 and VEGFR2 after 7 days of culture. According to the proportion of EPC fraction, patients were divided into 2 groups (cut-off value=median). Although no difference was seen in myocardial damage shown by mean peak CK leakage and mean area at risk between the differentiated group (n=26) and nondifferentiated group (n=25), the number of attached cell was greater in differentiated group than in the nondifferentiated group ( P =0.023). Left ventricular function and ischemic damaged area were assessed by scintigraphic images of 123 I-BMIPP in the acute phase and 99m Tc-tetrofosmin in the chronic phase. We found that a greater increase in myocardial salvage ( P =0.0091), decrease in end-systolic volume ( P =0.012), and recovery of ejection fraction ( P =0.011) occurred in the group with differentiated EPCs than in the nondifferentiated group. Conclusions— In patients with primary AMI, the capability of EPCs to differentiate influences the functional improvement and infarct size reduction, indicating that manipulation of EPCs could be a novel therapeutic target to salvage ischemic damage.

Objective Prostacyclin (PGI2) is a potent ligand of peroxisome proliferator-activated receptor δ (PPARδ) that regulates cell growth and differentiation. The aim of this study was to elucidate how endogenous PGI2 overexpression affects the expressions of PPARδ and mitogen-activated protein kinases (MAPKs) in the development of neointimal formation in experimental angioplasty with adenovirus-mediated PGI2 synthase (Ad-PGIS) gene transfer. Methods and results In human aortic smooth muscle cells, protein blotting analysis showed that PGI2 overproduction decreased the levels of phosphorylated p38 MAPK (P-p38 MAPK) (2.0-fold versus 0.83-fold relative to control). Immunohistochemical analysis in balloon-injured arteries revealed diffuse expression of PPARδ in the neointima of control vessels, with no expression in uninjured vessels. The level of PPARδ expression was lower in Ad-PGIS-treated arteries than in control vessels, with the PPARδ localized in the neointima adjacent to endothelium. Staining of P-p38 MAPK showed a similar pattern to PPARδ among the three groups. Morphometric analysis at day 14 revealed that Ad-PGIS reduced the intima-to-media ratio by up to 59%. Conclusions Ad-PGIS gene transfer reduced PPARδ expression and inhibited neointimal formation after balloon injury in accordance with the reduction in the phosphorylation of p38 MAPK.