Background-Inflammatory mediators that originate in vascular and extravascular tissues promote coronary lesion formation. Adipose tissue may function as an endocrine organ that contributes to an inflammatory burden in patients at risk of cardiovascular complications. In this study, we sought to compare expression of inflammatory mediators in epicardial and subcutaneous adipose stores in patients with critical CAD. Methods and Results-Paired samples of epicardial and subcutaneous adipose tissues were harvested at the outset of elective CABG surgery (nϭ42; age 65Ϯ10 years).

Patients with ULMCA disease treated with PCI had favorable early outcomes in comparison with the CABG group. At 1 year, LVEF had improved significantly only in the PCI group. After more than 2 years, MACCE-free survival was similar in both groups with a trend toward improved survival after PCI.

The maximal exercise capacity of patients with chronic heart failure is frequently reduced. To investigate whether this exercise intolerance is caused by inadequate nutritive flow to skeletal muscle, we compared cardiac outputs, leg blood flow, and leg metabolism during maximal bicycle exercise in seven patients with normal maximal oxygen uptake (V02) (>20 ml/min/kg; group A), eight patients with heart failure and moderately reduced maximal V02 (15 to 18 ml/min/kg; group B), and eight patients with heart failure and markedly reduced maximal V02 (<14 ml/min/kg; group C). As the severity of exercise intolerance increased from group A to group C there was a progressive decline in cardiac output and leg blood flow at any given workload accompanied by a progressive decline in maximal cardiac output (liters/min) (A, 12.4 + 1.0; B, 8.7 ± 0.9; C, 5.5 ± 0.7), maximal leg flow (liters/min) (A, 4.0 0.3; B, 2.6 + 0.4; C, 1.4 + 0.2), and maximal leg V02 (ml/min) (A, 564 + 49; B, 403 + 41; C, 213 ± 35 ml/min). All patients terminated exercise because of severe leg fatigue. At termination of exercise, all three groups exhibited similar marked levels of leg 02 extraction (%) (A, 80 ± 2; B, 83 + 3; C, 89 + 1) and high femoral-arterial lactate gradients (mg/dl) (A, 15.4 + 2.6; B, 18.3 ± 3.5; C, 19.2 ± 3.6), suggesting that exercise was limited when a critical level of muscle underperfusion was reached. These data suggest that the reduced maximal exercise capacity of patients with chronic heart failure is primarily due to impaired nutritive flow to skeletal muscle and resultant muscular fatigue. Circulation 69, No. 6, 1079No. 6, -1087No. 6, , 1984. THE MAXIMAL exercise capacity of patients with chronic heart failure is frequently reduced.'-1 It has recently been suggested that this exercise intolerance is primarily caused by inadequate blood flow to working skeletal muscle,3'4 since patients with heart failure have reduced cardiac outputs, early increases in lactate concentration, and augmented limb 02 extraction during exercise.3 6 However, it has yet to be directly demonstrated that perfusion of working skeletal muscle is impaired during upright maximal exercise in such patients.Accordingly, this study was undertaken to determine whether blood flow in skeletal muscle is reduced during maximal exercise in patients with chronic heart

Background-Multiple pathways contribute to accelerated coronary atherosclerosis in diabetics, including increased oxidative stress and inflammatory burden. Accordingly, the mechanisms of abnormal formation of reactive oxygen species and the changes in inflammatory gene expression were examined in diabetic coronary arteries. Methods and Results-In pigs with streptozotocin-induced diabetes, superoxide formation was augmented in coronary media and adventitia because of increased NAD(P)H oxidase activity (3 months) accompanied by upregulated expression of its cytosolic subunit, p22 phox . Diabetes-induced oxidative stress resulted in the inflammatory response in the adventitia (increased expression of interleukin-6, tumor necrosis factor-␣, monocyte chemotactic protein-1, vascular cell adhesion molecule-1 [VCAM-1]) and in the media (VCAM-1). To examine the mechanisms of these changes, studies with isolated coronary fibroblasts were undertaken. Advanced glycation end products (AGEs), rather than glucose itself, upregulated expression of interleukin-6, VCAM-1, and monocyte chemotactic protein-1 mRNAs. These results were paralleled by increased interleukin-6 secretion (PϽ0.01) and augmented leukocyte adhesion to AGEstimulated coronary cells (PϽ0.001). AGEs increased expression of phosphorylated forms of mitogen-activated protein kinases in coronary cells (ERK1/2 and JNK) and resulted in redox-sensitive expression of inflammatory genes that was inhibited by several inhibitors of oxidative pathways [NAD(P)H oxidase inhibitors, N-acetylcysteine, and pyrrolidine dithiocarbamate]. Conclusions-Diabetes