Myoblast-seeded biodegradable scaffolds to prevent post-myocardial infarction evolution toward heart failure

OBJECTIVE(S): Even though the mechanism is not clearly understood, direct intramyocardial cell transplantation has demonstrated potential to treat patients with severe heart failure. We previously reported on the bioengineering of myoblast-based constructs. We investigate here the functional outcome of infarcted hearts treated by implantation of myoblast-seeded scaffolds. METHODS: Adult Lewis rats with echocardiography-confirmed postinfarction reduced ejection fraction (48.3% +/- 1.1%) were randomized to (1) implantation of myoblast-seeded polyurethane patches at the site of infarction (PU-MyoB, n = 11), (2) implantation of nonseeded polyurethane patches (PU, n = 11), (3) sham operation (Sham, n = 12), and (4) direct intramyocardial myoblast injection (MyoB, n = 11). Four weeks later, the functional assessment by echocardiography was repeated, and we additionally performed left ventricular catheterization plus histologic studies. RESULTS: The ejection fraction significantly decreased in the PU (39.1% +/- 2.3%; P = .02) and Sham (39.9% +/- 3.5%; P = .04) groups, whereas it remained stable in the PU-MyoB (48.4% +/- 3.1%) and MyoB (47.9% +/- 3.0%) groups during the observation time. Similarly, left ventricular contractility was significantly higher in groups PU-MyoB (4960 +/- 266 mm Hg/s) and MyoB (4748 +/- 304 mm Hg/s) than in groups PU (3909 +/- 248 mm Hg/s, P = .01) and Sham (4028 +/- 199 mm Hg/s, P = .01). Immunohistology identified a high density of myoblasts within the seeded scaffolds without any migration toward the host cardiac tissue and no evidence of cardiac cell differentiation. CONCLUSIONS: Myoblast-seeded polyurethane scaffolds prevent post-myocardial infarction progression toward heart failure as efficiently as direct intramyocardial injection. The immunohistologic analysis suggests that an indirect mechanism, potentially a paracrine effect, may be assumed.

Heart rate variability does not discriminate between different levels of haemodynamic responsiveness during surgical anaesthesia

BACKGROUND: Hypnotic depth but not haemodynamic responsiveness is measured with EEG-based monitors. In this study we compared heart rate variability (HRV) in unstimulated patients and stimulation-induced HRV at different levels of anaesthesia. METHODS: A total of 95 ASA I or II patients were randomly assigned to five groups (Group 1: BIS 45(5), remifentanil 1 ng ml(-1); Group 2: BIS 45(5), remifentanil 2 ng ml(-1); Group 3: BIS 45(5), remifentanil 4 ng ml(-1); Group 4: BIS 30(5), remifentanil 2 ng ml(-1); Group 5: BIS 60(5), remifentanil 2 ng ml(-1)). A time- and frequency-domain analysis of the RR interval (RRI) from the electrocardiogram was performed. HRV before induction, before and after a 5 s tetanic stimulus of the ulnar nerve, and before and after tracheal intubation was compared between groups, between stimuli, and between responders to intubation [systolic arterial pressure (SAP) increase >20 mm Hg, a maximal heart rate (HR) after intubation >90 min(-1) or both] and non-responders (anova). RESULTS: Induction of anaesthesia significantly lowered HR and HRV. Mean RRI before stimulation was higher in G3 than in G1, G2, and G4 (P < 0.001), whereas the other HRV parameters were similar. Intubation induced a greater HRV response than tetanic stimulation. The mean RRI after intubation was lower in G3 compared with the other groups and the sd of the RRI after tetanic stimulation was lower in G3 compared with G5. Otherwise, unstimulated HRV and stimulation-induced HRV were similar in responders and non-responders. CONCLUSION: HRV parameters discriminate between awake and general anaesthesia, are different after tracheal intubation and a 5 s ulnar nerve stimulation, but do not discriminate between different levels of haemodynamic responsiveness during surgical anaesthesia.

Staged bilateral carotid stenting, an effective strategy in high-risk patients - insights from a prospective multicenter trial

OBJECTIVE: To prospectively evaluate outcomes of high-risk patients undergoing bilateral carotid artery stenting (CAS). METHODS: A total of 747 patients at increased risk for carotid endarterectomy (CEA) were enrolled in a prospective registry at 47 US sites of the Boston Scientific EPI: A Carotid Stenting Trial for Risk Surgical Patients (BEACH) trial. Among them, 78 (10.4%) patients underwent contralateral CAS > 30 days after the primary CAS procedure. Patients were followed at 1, 6, and 12 months, and annually thereafter for 3 years. The primary endpoint was the cumulative incidence of non Q-wave myocardial infarction within 24 hours, periprocedural (groups with regard to any of the components of the primary or secondary endpoints. The univariate 1-year major adverse event (MAE) free survival was 93.6% and 91.6% in the bilateral and pivotal groups, respectively (P = .55). Multivariate logistic regression analysis with adjustment for various clinical baseline factors revealed no differences in the primary endpoint when comparing the bilateral with the pivotal groups at 30 days (odds ratio [OR]: 0.8673, 95% confidence interval [CI] 0.4590-1.6389, P = .66) or 1 year (OR: 0.9102, 95% CI 0.5503-1.5053, P = .73). CONCLUSIONS: Bilateral carotid stenting is an effective treatment strategy in patients determined to be at high-risk for CEA with no increase in morbidity or mortality results extended out to one year in a prospective multicenter trial.

The effect of pulsed jet lavage in vertebroplasty on injection forces of polymethylmethacrylate bone cement, material distribution, and potential fat embolism: a cadaver study

STUDY DESIGN: In vitro testing of vertebroplasty techniques including pulsed jet-lavage for fat and marrow removal in human cadaveric lumbar and thoracic vertebrae. OBJECTIVE: To develop jet-lavage techniques for vertebroplasty and investigate their effect on cement distribution, injection forces, and fat embolism. SUMMARY OF BACKGROUND DATA: The main complications of cement vertebroplasty are cement leakage and pulmonary fat embolism, which can have fatal consequences and are difficult to prevent reliably by current vertebroplasty techniques. METHODS: Twenty-four vertebrae (Th8-L04) from 5 osteoporotic cadaver spines were grouped in triplets depending on bone mineral density (BMD). Before polymethylmethacrylate (PMMA) vertebroplasty, a pulsatile jet-lavage for removal of intertrabecular fat and bone marrow was performed in 2 groups with 8 specimens each, performing radial and axial irrigation from the biopsy needles. One hundred mL of Ringer solution were injected through 1 pedicle and regained by low vacuum via the contralateral pedicle. Eight control vertebrae were not irrigated. All specimens underwent standardized PMMA cement augmentation injecting 20% of the vertebral volume. Injection forces, cement distribution, and extravasations were quantified. RESULTS: All irrigation solution could be retrieved with the vacuum applied. A Kruskal-Wallis test revealed significantly higher injection forces of the control group as compared with the irrigated groups (P = 0.021). Dilatation of the syringe at forces above 300 N occurred in 75% of the untreated compared with 12.5% of the lavaged specimens. CT distribution analysis showed more homogenous cement distribution of the cement and significantly less extravasation in the irrigated specimens. CONCLUSION: The developed lavage technique for vertebroplasty showed to be feasible and reproducible. The reduction of injection forces would allow the use of more viscous PMMA cement lowering the risk for cement embolization and results in a safer procedure. The wash-out of bone marrow and the possible reduction of pulmonary fat embolism have to be verified with in vivo models.

CHARACTERIZATION OF ASPHALT MATERIALS CONTAINING BIO OIL FROM MICHIGAN WOOD

The objective of this research is to develop sustainable wood-blend bioasphalt and characterize the atomic, molecular and bulk-scale behavior necessary to produce advanced asphalt paving mixtures. Bioasphalt was manufactured from Aspen, Basswood, Red Maple, Balsam, Maple, Pine, Beech and Magnolia wood via a 25 KWt fast-pyrolysis plant at 500 °C and refined into two distinct end forms - non-treated (5.54% moisture) and treated bioasphalt (1% moisture). Michigan petroleum-based asphalt, Performance Grade (PG) 58-28 was modified with 2, 5 and 10% of the bioasphalt by weight of base asphalt and characterized with the gas chromatography-mass spectroscopy (GC-MS), Fourier Transform Infra-red (FTIR) spectroscopy and the automated flocculation titrimetry techniques. The GC-MS method was used to characterize the Carbon-Hydrogen-Nitrogen (CHN) elemental ratio whiles the FTIR and the AFT were used to characterize the oxidative aging performance and the solubility parameters, respectively. For rheological characterization, the rotational viscosity, dynamic shear modulus and flexural bending methods are used in evaluating the low, intermediate and high temperature performance of the bio-modified asphalt materials. 54 5E3 (maximum of 3 million expected equivalent standard axle traffic loads) asphalt paving mixes were then prepared and characterized to investigate their laboratory permanent deformation, dynamic mix stiffness, moisture susceptibility, workability and constructability performance. From the research investigations, it was concluded that: 1) levo, 2, 6 dimethoxyphenol, 2 methoxy 4 vinylphenol, 2 methyl 1-2 cyclopentandione and 4-allyl-2, 6 dimetoxyphenol are the dominant chemical functional groups; 2) bioasphalt increases the viscosity and dynamic shear modulus of traditional asphalt binders; 3) Bio-modified petroleum asphalt can provide low-temperature cracking resistance benefits at -18 °C but is susceptible to cracking at -24 °C; 3) Carbonyl and sulphoxide oxidation in petroleum-based asphalt increases with increasing bioasphalt modifiers; 4) bioasphalt causes the asphaltene fractions in petroleum-based asphalt to precipitate out of the solvent maltene fractions; 5) there is no definite improvement or decline in the dynamic mix behavior of bio-modified mixes at low temperatures; 6) bio-modified asphalt mixes exhibit better rutting performance than traditional asphalt mixes; 7) bio-modified asphalt mixes have lower susceptibility to moisture damage; 8) more field compaction energy is needed to compact bio-modified mixes.

Flotillins interact with PSGL-1 in neutrophils and, upon stimulation, rapidly organize into membrane domains subsequently accumulating in the uropod

BACKGROUND: Neutrophils polarize and migrate in response to chemokines. Different types of membrane microdomains (rafts) have been postulated to be present in rear and front of polarized leukocytes and disruption of rafts by cholesterol sequestration prevents leukocyte polarization. Reggie/flotillin-1 and -2 are two highly homologous proteins that are ubiquitously enriched in detergent resistant membranes and are thought to shape membrane microdomains by forming homo- and hetero-oligomers. It was the goal of this study to investigate dynamic membrane microdomain reorganization during neutrophil activation. METHODOLOGY/PRINCIPAL FINDINGS: We show now, using immunofluorescence staining and co-immunoprecipitation, that endogenous flotillin-1 and -2 colocalize and associate in resting spherical and polarized primary neutrophils. Flotillins redistribute very early after chemoattractant stimulation, and form distinct caps in more than 90% of the neutrophils. At later time points flotillins accumulate in the uropod of polarized cells. Chemotactic peptide-induced redistribution and capping of flotillins requires integrity and dynamics of the actin cytoskeleton, but does not involve Rho-kinase dependent signaling related to formation of the uropod. Both flotillin isoforms are involved in the formation of this membrane domain, as uropod location of exogenously expressed flotillins is dramatically enhanced by co-overexpression of tagged flotillin-1 and -2 in differentiated HL-60 cells as compared to cells expressing only one tagged isoform. Flotillin-1 and -2 associate with P-selectin glycoprotein ligand 1 (PSGL-1) in resting and in stimulated neutrophils as shown by colocalization and co-immunoprecipitation. Neutrophils isolated from PSGL-1-deficient mice exhibit flotillin caps to the same extent as cells isolated from wild type animals, implying that PSGL-1 is not required for the formation of the flotillin caps. Finally we show that stimulus-dependent redistribution of other uropod-located proteins, CD43 and ezrin/radixin/moesin, occurs much slower than that of flotillins and PSGL-1. CONCLUSIONS/SIGNIFICANCE: These results suggest that flotillin-rich actin-dependent membrane microdomains are importantly involved in neutrophil uropod formation and/or stabilization and organize uropod localization of PSGL-1.