Cellular Imaging of Human Atherosclerotic Lesions by Intravascular Electric Impedance Spectroscopy

Background: Newer techniques are required to identify atherosclerotic lesions that are prone to rupture. Electric impedance spectroscopy (EIS) is able to provide information about the cellular composition of biological tissue. The present study was performed to determine the influence of inflammatory processes in type Va (lipid core, thick fibrous cap) and Vc (abundant fibrous connective tissue while lipid is minimal or even absent) human atherosclerotic lesions on the electrical impedance of these lesions measured by EIS. Methods and Results: EIS was performed on 1 aortic and 3 femoral human arteries at 25 spots with visually heavy plaque burden. Severely calcified lesions were excluded from analysis. A highly flexible micro-electrode mounted onto a balloon catheter was placed on marked regions to measure impedance values at 100 kHz. After paraffin embedding, visible marked cross sections (n = 21) were processed. Assessment of lesion types was performed by Movats staining. Immunostaining for CD31 (marker of neovascularisation), CD36 (scavenger cells) and MMP-3 (matrix metalloproteinase-3) was performed. The amount of positive cells was assessed semi-quantitatively. 15 type Va lesions and 6 type Vc lesions were identified. Lesions containing abundant CD36-, CD31- and MMP-3-positive staining revealed significantly higher impedance values compared to lesions with marginal or without positive staining (CD36+455650 V vs. CD36- 346653 V, p = 0.001; CD31+436643 V vs. CD31- 340655 V, p = 0.001; MMP-3+ 400668 V vs. MMP-3- 323633 V, p = 0.03)

Expansion of the Multi-Link Frontier™ Coronary Bifurcation Stent: Micro-Computed Tomographic Assessment in Human Autopsy and Porcine Heart Samples

BACKGROUND: Treatment of coronary bifurcation lesions remains challenging, beyond the introduction of drug eluting stents. Dedicated stent systems are available to improve the technical approach to the treatment of these lesions. However dedicated stent systems have so far not reduced the incidence of stent restenosis. The aim of this study was to assess the expansion of the Multi-Link (ML) Frontier™ stent in human and porcine coronary arteries to provide the cardiologist with useful in-vitro information for stent implantation and selection. METHODOLOGY/PRINCIPAL FINDINGS: Nine ML Frontier™ stents were implanted in seven human autopsy heart samples with known coronary artery disease and five ML Frontier™ stents were implanted in five porcine hearts. Proximal, distal and side branch diameters (PD, DD, SBD, respectively), corresponding opening areas (PA, DA, SBA) and the mean stent length (L) were assessed by micro-computed tomography (micro-CT). PD and PA were significantly smaller in human autopsy heart samples than in porcine heart samples (3.54±0.47 mm vs. 4.04±0.22 mm, p = 0.048; 10.00±2.42 mm(2) vs. 12.84±1.38 mm(2), p = 0.034, respectively) and than those given by the manufacturer (3.54±0.47 mm vs. 4.03 mm, p = 0.014). L was smaller in human autopsy heart samples than in porcine heart samples, although data did not reach significance (16.66±1.30 mm vs. 17.30±0.51 mm, p = 0.32), and significantly smaller than that given by the manufacturer (16.66±1.30 mm vs. 18 mm, p = 0.015). CONCLUSIONS/SIGNIFICANCE: Micro-CT is a feasible tool for exact surveying of dedicated stent systems and could make a contribution to the development of these devices. The proximal diameter and proximal area of the stent system were considerably smaller in human autopsy heart samples than in porcine heart samples and than those given by the manufacturer. Special consideration should be given to the stent deployment procedure (and to the follow-up) of dedicated stent systems, considering final intravascular ultrasound or optical coherence tomography to visualize (and if necessary optimize) stent expansion

Incidence and electrophysiological characteristics of spontaneous ventricular tachyarrhythmias in high risk coronary patients and prophylactic implantation of a defibrillator

Objectives: To assess the incidence and electrophysiological characteristics of spontaneous ventricular tachyarrhythmias after implantable cardioverter-defibrillator (ICD) implantation for primary prevention. Design: Prospective observational study. Patients: 41 consecutive patients, who fulfilled MADIT (multicenter automatic defibrillator implantation trial) I criteria, except for suppressibility by procainamide, and who received a prophylactic ICD. Interventions: Subpectoral implantation of an ICD. Main outcome measures: Incidence of ventricular tachyarrhythmias and their electrophysiological characteristics with respect to timing of the arrhythmia, tachyarrhythmia cycle length, mode of termination, and clinical relevance. Results: During a mean (SD) follow up of 30 (21) months 18 of 41 (43.9%) patients experienced 142 appropriate ICD treatments. The mean (SD) time to first event was 9.6 (15.1) months. One patient had ventricular fibrillation (VF), 12 patients ventricular tachycardia (VT), and five both VT and VF. The mean (SD) cycle length of monomorphic VT was 306 (42) ms. Of 142 episodes, 117 (82.3%) were terminated by antitachycardia pacing and another 25 (17.6%) by ICD discharges. Cumulative survival of hypothetical death, defined as treated VT with a cycle length < 260 ms or VF, was 83.2% after one year and 78.4% after two years. Conclusions: Patients with a left ventricular ejection fraction < 35%, a history of myocardial infarction, non-sustained VT, and inducible VT/VF are at high risk of VT/VF early after implantation. Therefore, implantation of a tiered treatment defibrillator seems to be justified

Effect of intravenous FX06 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction results of the F.I.R.E. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury) trial

OBJECTIVES: The purpose of this study was to investigate whether FX06 would limit infarct size when given as an adjunct to percutaneous coronary intervention. BACKGROUND: FX06, a naturally occurring peptide derived from human fibrin, has been shown to reduce myocardial infarct size in animal models by mitigating reperfusion injury. METHODS: In all, 234 patients presenting with acute ST-segment elevation myocardial infarction were randomized in 26 centers. FX06 or matching placebo was given as intravenous bolus at reperfusion. Infarct size was assessed 5 days after myocardial infarction by late gadolinium enhanced cardiac magnetic resonance imaging. Secondary outcomes included size of necrotic core zone and microvascular obstruction at 5 days, infarct size at 4 months, left ventricular function, troponin I levels, and safety. RESULTS: There were no baseline differences between groups. On day 5, there was no significant difference in total late gadolinium enhanced zone in the FX06 group compared with placebo (reduction by 21%; p = 0.207). The necrotic core zone, however, was significantly reduced by 58% (median 1.77 g [interquartile range 0.0, 9.09 g] vs. 4.20 g [interquartile range 0.3, 9.93 g]; p > 0.025). There were no significant differences in troponin I levels (at 48 h, -17% in the FX06 group). After 4 months, there were no longer significant differences in scar size. There were numerically fewer serious cardiac events in the FX06-treated group, and no differences in adverse events. CONCLUSIONS: In this proof-of-concept trial, FX06 reduced the necrotic core zone as one measure of infarct size on magnetic resonance imaging, while total late enhancement was not significantly different between groups. The drug appears safe and well tolerated. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury [F.I.R.E.]; NCT00326976)

Ecotype Differentiation in the Face of Gene Flow within the Diving Beetle Agabus bipustulatus (Linnaeus, 1767) in Northern Scandinavia

The repeated occurrence of habitat-specific polyphyletic evolved ecotypes throughout the ranges of widely distributed species implies that multiple, independent and parallel selection events have taken place. Ecological transitions across altitudinal gradients over short geographical distances are often associated with variation in habitat-related fitness, these patterns suggest the action of strong selective forces. Genetic markers will therefore contribute differently to differences between ecotypes in local hybrid zones. Here we have studied the adaptive divergence between ecotypes of the water beetle Agabus bipustulatus along several parallel altitudinal gradients in northern Scandinavia. This water beetle is well known for its remarkable morphological variation associated with mountain regions throughout the western Palaearctic. Two morphological ecotypes are recognised: a montane type with reduced flight muscles and a lowland type with fully developed muscles. Using a multilocus survey of allozyme variation and a morphological analysis with landmark-based morphometrics, across thirty-three populations and seven altitudinal gradients, we studied the local adaptive process of gene flow and selection in detail. Populations were sampled at three different elevations: below, at and above the tree line. The results indicate that the levels of divergence observed between ecotypes in morphology and allele frequencies at alpha-Glycerophosphate dehydrogenase relative to those shown by neutral molecular markers reflects local diversifying selection in situ. Four main lines of evidence are shown here: (1) A repeated morphological pattern of differentiation is observed across all altitudinal transects, with high reclassification probabilities. (2) Allele and genotype frequencies at the alpha-Gpdh locus are strongly correlated with altitude, in sharp contrast to the presumable neutral markers. (3) Genetic differentiation is two to three times higher among populations across the tree line than among populations at or below. (4) Genetic differentiation between ecotypes within independent mountain areas is reflected by different sets of allozymes