The ability of multidetector computed tomography (MDCT) to detect stress-induced myocardial perfusion abnormalities is of great clinical interest as a potential tool for the combined evaluation of coronary stenosis and its significance. However, stress testing requires repeated scanning, which is associated with additional radiation exposure and iodine contrast. Our goal was to determine the effects of reduced tube voltage and contrast dose on the ability to detect perfusion abnormalities. We studied 40 patients referred for CT coronary angiography (CTCA). Images were acquired at rest and during regadenoson stress (256-channel scanner, Philips) using 120kV tube voltage with 80–90 ml contrast in 20 patients and 100kV with 55–70 ml contrast in the remaining 20 patients. Custom software was used to define 3D myocardial segments and measure segmental x-ray attenuation. In each group of patients, myocardial attenuation was averaged for segments supplied by arteries with stenosis causing >50% narrowing on CTCA, and separately for segments supplied by arteries without significant stenosis. In both groups, myocardial attenuation was equally reduced in segments supplied by diseased arteries, despite the 74% reduction in radiation and the 28% reduction in contrast. Regadenoson stress MDCT imaging can detect hypoperfused myocardium even when imaging settings are optimized to provide a significant reduction in radiation and contrast doses.
Background: Transthoracic Doppler echocardiography (TTDE) assessment of coronary flow velocity reserve (CFVR) has been validated in Asian and European centers. This methodology has not gained acceptability in the United States due to the bias that coronary flow velocity (CFV) by TTDE might be difficult in an obese population with relatively poor acoustic windows. Methods: Baseline CFV in the left anterior descending coronary artery (LAD) by TTDE was obtained in 67 nonselected American patients. A subset of 38/67 received adenosine infusion for measuring CFVR of the LAD. Purpose: The aim of this study was twofold: (1) to determine the feasibility of measuring CFV and CFVR in the LAD by TTDE in a relatively obese American population, and (2) to compare CFV and CFVR values in this population with those previously obtained in a group of Japanese patients. Results: The mean body mass index (BMI) of the American population (28 ± 6 kg/m 2 , range: 18–46 kg/m 2 ) was significantly higher than that of the Japanese group (23 ± 4 kg/m 2 , range: 15–37 kg/m 2 ). Twenty‐five American patients were classified as obese (BMI >30kg/m 2 ). Baseline CFV was obtained in 60/67 patients (feasibility: 90%) with a 10% need for intravenous contrast agent to enhance the delineation of the CFV envelope. The success rate in recording CFVR in American patients (92%) was nearly identical to that of a Japanese group (99%). The time‐averaged peak diastolic coronary flow velocity increased from 15.6 ± 5.5 cm/sec at baseline to 47.1 ± 17.9 cm/sec during adenosine infusion, and CFVR was calculated to be 3.22 ± 1.15 (range: 0.94–5.69). Intraobserver and interobserver variability for the CFV recording was 4.7 and 6.2%, respectively. Conclusions: These results suggest that the noninvasive measurement of CFV and CFVR of the LAD is feasible even in a relatively obese American population. Furthermore, the success rates for recording CFV and CFVR are similar to those measured in a Japanese population. This methodology has the potential to provide useful physiological information on the coronary circulation in American patients.
We tested the hypothesis that quantitative 3D analysis of myocardial perfusion from MDCT images obtained during regadenoson stress would more accurately detect the presence of significant coronary artery disease (CAD) than the same analysis when performed on resting MDCT images. Fifty consecutive patients referred for CT coronary angiography (CTCA) underwent additional imaging with regadenoson (0.4mg, Astellas) using prospective gating (256-channel, Philips). Custom software was used to calculate for each myocardial segment an index of severity and extent of perfusion abnormality, Qh, which was compared to perfusion defects predicted by the presence and severity of coronary stenosis on CTCA. In segments supplied by arteries with luminal narrowing >50%, myocardial attenuation was slightly reduced compared to normally perfused segments at rest (91±21 vs. 93±26 HU, NS), and to a larger extent at stress (102±21 vs. 112±20 HU, p<0.05). In contrast, index Qh was significantly increased in these segments at rest (0.40±0.48 vs. 0.26±0.41, p<0.05) and reached a nearly 3-fold difference at stress (0.66±0.74 vs. 0.28±0.51, p<0.05). The addition of regadenoson improved the diagnosis of CAD, as reflected by an increase in sensitivity (from 0.57 to 0.91) and improvement in accuracy (0.65 to 0.77). In conclusion, quantitative 3D analysis of MDCT images allows objective detection of CAD, the accuracy of which is improved by regadenoson stress.
Rationale : S100A12 is a small calcium binding protein that is a ligand of RAGE (receptor for advanced glycation end products). RAGE has been extensively implicated in inflammatory states such as atherosclerosis, but the role of S100A12 as its ligand is less clear. Objective : To test the role of S100A12 in vascular inflammation, we generated and analyzed mice expressing human S100A12 in vascular smooth muscle under control of the smooth muscle 22α promoter because S100A12 is not present in mice. Methods and Results : Transgenic mice displayed pathological vascular remodeling with aberrant thickening of the aortic media, disarray of elastic fibers, and increased collagen deposition, together with increased latent matrix metalloproteinase-2 protein and reduction in smooth muscle stress fibers leading to a progressive dilatation of the aorta. In primary aortic smooth muscle cell cultures, we found that S100A12 mediates increased interleukin-6 production, activation of transforming growth factor β pathways and increased metabolic activity with enhanced oxidative stress. To correlate our findings to human aortic aneurysmal disease, we examined S100A12 expression in aortic tissue from patients with thoracic aortic aneurysm and found increased S100A12 expression in vascular smooth muscle cells. Conclusions : S100A12 expression is sufficient to activate pathogenic pathways through the modulation of oxidative stress, inflammation and vascular remodeling in vivo.
Gastrointestinal stasis during sepsis may be associated with gastrointestinal smooth muscle dysfunction. Endotoxin [lipopolysaccharide (LPS)] impairs smooth muscle contraction, in part through inducible nitric oxide synthase (NOS II) and enhanced nitric oxide production. We studied the roles of tumor necrosis factor-α (TNF) and interleukin-1 (IL-1) in this process by using TNF binding protein (TNFbp) and IL-1 receptor antagonist (IL-1ra). Rats were treated with TNFbp and IL-1ra, or their vehicles, 1 h before receiving LPS or saline. At 5 h after LPS, contractility was measured in strips of ileal longitudinal smooth muscle, and NOS II activity was measured in full-thickness segments of ileum. LPS decreased maximum stress (mean ± SE) from 508 ± 55 (control) to 355 ± 33 g/cm 2 ( P < 0.05). Pretreatment with TNFbp plus IL-1ra prevented the LPS-induced decrease. Separate studies of TNFbp alone or IL-1ra alone indicated that, at the doses and timing used, TNFbp was more effective. LPS also increased NOS II activity by >10-fold ( P < 0.01) over control. This increase was prevented by TNFbp plus IL-1ra ( P = not significant vs. control). We conclude that the LPS-induced increase in NOS II activity and the decrease in ileal muscle contractility are mediated by TNF and IL-1.
Background: Transthoracic echocardiography (TTE) is ordered frequently in patients with suspected pulmonary embolism (PE). Multiple indices have been suggested to play a useful diagnostic role. We sought to determine the relative predictive accuracy of suggested quantitative indices among patients referred for CT scanning for exclusion of PE. Methods: We retrospectively identified 67 consecutive patients who underwent CT for the exclusion of PE, and had a TTE within 48 hours of CT. Echo indices suggested to play a role in the diagnosis of PE were measured RV/LV area ratio, RV/LV end diastolic dimension ratio, the “McConnell” sign, interventricular septal shift (“D‐sign”), Pulmonary artery diameter, tricuspid regurgitation velocity, and “60/60 sign” (TR velocity < 3.9 m/sec plus pulmonary artery acceleration time < 60 msec). Results: CT confirmed PE in 41 (61%). Mean age was 58 (18–92). Forty‐five were female. Subjects with PE were younger, and more likely to be tachycardic and require ICU admission. Of the echocardiographic indices, RV/LV EDD ratio > 0.7 was the most accurate predictor (sensitivity 66%, specificity 77%). The McConnell sign was the most specific (96%), however, with poor sensitivity (16%). Mean TR velocities did not differ between those with and without PE (270 ± 74 vs. 294 ± 83, P = 0.25). Conclusions: RV/LV EDD ratio > 0.7 has good accuracy for the diagnosis of acute PE. RV/LV area ratio > 0.7 and McConnell sign are specific but not sensitive indicators of acute pulmonary embolism. The presence of these findings should prompt further diagnostic testing for PE.
