Non-invasive characterization of the area-at-risk using magnetic resonance imaging in chronic ischaemia.

AIMS: we investigated the performance of quantitative stress perfusion magnetic resonance imaging (MRI) as a basis for identifying and characterizing the area-at-risk subtending a chronic coronary artery (CA) stenosis. METHODS AND RESULTS: pigs underwent a percutaneous copper-coated stent implantation in the circumflex CA (n = 11) or a sham operation (n = 5). After 6 weeks, angiography and MRI were performed including cine (rest, low- and high-dose dobutamine stress), dual-bolus first-pass perfusion (rest and adenosine stress), and contrast-enhanced imaging to quantify myocardial infarction (MI). Myocardial blood flow (MBF) was quantified based on Fermi-model deconvolution and compared with microsphere measurements. On the basis of Evan's blue staining, MBF thresholds to define the area-at-risk were determined by receiver-operating characteristic (ROC) analysis. CA stenosis was 94 ± 7% and infarct size (IS) 7.3 ± 3.1% of left ventricular mass. Segmental thresholds of hyperaemic MBF yielded the best performance for detecting area-at-risk. There was a good correlation between MRI and microsphere perfusion (r(2) = 0.84, P < .0001). The area-at-risk presented a mixed substrate of non-infarcted (non-MI), <50% infarcted (MI+), and >50% infarcted (MI++) segments. MBF was reduced in at-risk vs. remote segments at rest (non-MI, 0.50 ± 0.21; MI+, 0.47 ± 0.14; MI++, 0.42 ± 0.14; remote, 0.84 ± 0.25 mL/min/g) and during stress (non-MI, 0.69 ± 0.09; MI+, 0.66 ± 0.14; MI++, 0.51 ± 0.11; remote, 1.70 ± 0.36 mL/min/g). Segmental wall thickening showed different responses to stress (remote, progressive increase during incremental stress; non-MI, increase at low-dose and discontinued at high-dose; MI+, initial increase and decrease at high-dose; MI++, progressive decrease). CONCLUSION: quantitative hyperaemic perfusion MRI accurately defines segments in the area-at-risk in chronic ischaemia, which present with different functional response to stress related to segmental IS.

Ultrastructural and functional remodeling of the coupling between Ca2+ influx and sarcoplasmic reticulum Ca2+ release in right atrial myocytes from experimental persistent atrial fibrillation.

RATIONALE: Persistent atrial fibrillation (AF) has been associated with structural and electric remodeling and reduced contractile function. OBJECTIVE: To unravel mechanisms underlying reduced sarcoplasmic reticulum (SR) Ca(2+) release in persistent AF. METHODS: We studied cell shortening, membrane currents, and [Ca(2+)](i) in right atrial myocytes isolated from sheep with persistent AF (duration 129+/-39 days, N=16), compared to matched control animals (N=21). T-tubule density, ryanodine receptor (RyR) distribution, and local [Ca(2+)](i) transients were examined in confocal imaging. RESULTS: Myocyte shortening and underlying [Ca(2+)](i) transients were profoundly reduced in AF (by 54.8% and 62%, P<0.01). This reduced cell shortening could be corrected by increasing [Ca(2+)](i). SR Ca(2+) content was not different. Calculated fractional SR Ca(2+) release was reduced in AF (by 20.6%, P<0.05). Peak Ca(2+) current density was modestly decreased (by 23.9%, P<0.01). T-tubules were present in the control atrial myocytes at low density and strongly reduced in AF (by 45%, P<0.01), whereas the regular distribution of RyR was unchanged. Synchrony of SR Ca(2+) release in AF was significantly reduced with increased areas of delayed Ca(2+) release. Propagation between RyR was unaffected but Ca(2+) release at subsarcolemmal sites was reduced. Rate of Ca(2+) extrusion by Na(+)/Ca(2+) exchanger was increased. CONCLUSIONS: In persistent AF, reduced SR Ca(2+) release despite preserved SR Ca(2+) content is a major factor in contractile dysfunction. Fewer Ca(2+) channel-RyR couplings and reduced efficiency of the coupling at subsarcolemmal sites, possibly related to increased Na(+)/Ca(2+) exchanger, underlie the reduction in Ca(2+) release.

The correlation between the SOS in trabecular bone and stiffness and density studied by finite-element analysis.

For the clinical assessment of osteoporosis (i.e., a degenerative bone disease associated with increased fracture risk), ultrasound has been proposed as an alternative or supplement to the dual-energy X-ray absorptiometry (DEXA) technique. However, the interaction of ultrasound waves with (trabecular) bone remains relatively poorly understood. The present study aimed to improve this understanding by simulating ultrasound wave propagation in 15 trabecular bone samples from the human lumbar spine, using microcomputed tomography-based finite-element modeling. The model included only the solid bone, without the bone marrow. Two structural parameters were calculated: the bone volume fraction (BV/TV) and the structural (apparent) elastic modulus (E(s)), and the ultrasound propagation parameter speed of sound (SOS). Relations between BV/TV and E(s) were similar to published experimental relations. At 1 MHz, correlations between SOS and the structural parameters BV/TV and Es were rather weak, but the results can be explained from the specific features of the trabecular structure and the intrinsic material elastic modulus E(i). In particular, the systematic differences between the three main directions provide information on the trabecular structure. In addition, at 1 MHz the correlation found between the simulated SOS values and those calculated from the simple bar equation was poor when the three directions are considered separately. Hence, under these conditions, the homogenization approach-including the bar equation-is not valid. However, at lower frequencies (50-300 kHz) this correlation significantly improved. It is concluded that detailed analysis of ultrasound wave propagation through the solid structure in various directions and with various frequencies, can yield much information on the structural and mechanical properties of trabecular bone.