Perfusion defect size predicts engraftment but not early retention of intra-myocardially injected cardiosphere-derived cells after acute myocardial infarction

Therapeutic cell retention and engraftment are critical for myocardial regeneration. Underlying mechanisms, including the role of tissue perfusion, are not well understood. In Wistar Kyoto rats, syngeneic cardiosphere-derived cells (CDCs) were injected intramyocardially, after experimental myocardial infarction. CDCs were labeled with [18F]-FDG (n = 7), for quantification of 1-h retention, or with sodium-iodide-symporter gene (NIS; n = 8), for detection of 24-h engraftment by reporter imaging. Perfusion was imaged simultaneously. Infarct size was 37 ± 9 and 38 ± 9% of LV in FDG and NIS groups. Cell signal was located in the infarct border zone in all animals. No significant relationship was observed between infarct size and 1-h CDC retention (r = −0.65; P = 0.11). However, infarct size correlated significantly with 24-h engraftment (r = 0.75; P = 0.03). Residual perfusion at the injection site was not related to cell retention/engraftment. Larger infarcts are associated with improved CDC engraftment. This observation encourages further investigation of microenvironmental conditions after ischemic damage and their role in therapeutic cell survival

Nonalcoholic Fatty Liver Disease: Rapid Evaluation of Liver Fat Content with In-Phase and Out-of-Phase MR Imaging

Purpose: To evaluate in-phase and out-of-phase magnetic resonance (MR) imaging in the estimation of liver fat content (LFC) in patients with nonalcoholic fatty liver disease (NAFLD), with hydrogen (H-1) MR spectroscopy as the reference standard. Materials and Methods: Written informed consent was obtained from all subjects, and the local ethics committee approved this prospective study protocol. A total of 33 patients with type 2 diabetes mellitus who were at high risk for NAFLD (23 men, 10 women; overall mean age, 62.8 years +/- .3 [standard deviation]; age range, 48-77 years) underwent 1.5-T MR imaging with H-1 MR spectroscopy and in-phase and out-of-phase imaging of the liver. Three fat indexes were calculated from the signal intensity (SI) measured on the images. Two radiologists independently graded SI changes between in-phase and out-of-phase images by means of visual inspection. The Pearson correlation coefficient was used to study the relationship between the obtained parameters of SI change and LFC measured with H-1 MR spectroscopy. Results: Fat indexes calculated from in-phase and out-of-phase images correlated linearly with LFC measured with H-1 MR spectroscopy (P Conclusion: In-phase and out-of-phase imaging can be used to rapidly estimate the LFC in patients with NAFLD. The cutoff value of 5.1% enables objective rapid and reliable discrimination of normal LFC from elevated LFC. (C) RSNA, 200

Inverse association between liver fat content and hepatic glucose uptake in patients with type 2 diabetes mellitus

The objective of this research was to study (1) the mutual relationship between liver fat content (LFC) and hepatic glucose uptake (HGU) in patients with type 2 diabetes mellitus and (2) the relationship between changes in LFC and HGU uptake induced by rosiglitazone in these patients. Liver fat was measured with proton magnetic resonance spectroscopy and insulin-stimulated HGU with [F-18]-labeled 2-fluoro-2-deoxyglucose positron emission tomography in 54 patients with type 2 diabetes mellitus and 8 healthy Subjects. Measurements were repeated in diabetic patients after a 16-week intervention period with rosiglitazone (n = 27) or placebo (n = 27). Patients with diabetes had lower HGU (24.5 +/- 14.2 vs 35.6 +/- 9.7 mu mol/[kg min], P <.01) and higher LFC (10.9% +/- 9.2% vs 2.5% +/- 1.4%, P <.001) compared with healthy subjects. Liver fat was inversely associated with HGU (r = -0.31, P <.05). but more strongly with whole-body insulin sensitivity and adiponectin levels. Rosiglitazone treatment reduced liver fat by 24.8% (P = .01 vs placebo) and increased HGU by 29.2% (P = .013 vs placebo). This decrease in LFC was best explained by the increment in suppression of nonesterified fatty acid levels during hyperinsulinemia (P <.001) and improved glycemic control (P = .034), but not by changes in HGU. A significant inverse relationship between LFC and HGU was observed, but changes were not related. This suggests that the beneficial effects of rosiglitazone on liver metabolism are indirect and can be partly explained by increased suppression of nonesterified fatty acid levels, leading to reduced liver fat. (C) 2008 Elsevier Inc. All rights reserved

Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [O-15]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2[F-18]fluoro-D-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 +/- 2.0%) and high (17.4 +/- 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level (P = 0.012) and muscle (P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake (P = 0.040) and glucose extraction rate (P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 (P <0.05) and lower coronary flow reserve (P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function