Cardiovascular radiation medicine最新文献

Objective

Cell therapy is becoming a viable strategy to improve revascularization and myocardial function after myocardial injury. We evaluated the effect of bone marrow-derived mononuclear cell (BMMNC) transplantation on collateral vessel development and myocardial function in a porcine model of chronically infarcted heart.

Methods

Myocardial infarction was produced in 13 domestic swine. At 4 weeks, animals were randomized to receive transepicardial injections of autologous BMMNCs (approximately 24×10⁶ cells, n=8) or phosphate buffered saline (PBS; control, n=5) into infarcted and border regions. Collateral growth, angiogenesis, and infarct size were assessed by angiography, immunohistochemistry, and histomorphometry.

Results

Regional contractility was assessed by transepicardial echocardiography at baseline and 4 weeks following treatment. Angiography revealed a trend toward increased collateral growth in the BMMNC group. Wall motion score index (myocardial function) was similar in both groups at baseline (1.63±0.16 vs. 1.25±0.25, P=.21) and at 4 weeks (1.83±0.22 vs. 1.63±0.38, P=.62). α-Actin-positive smooth muscle cells (SMCs) and Factor VIII positive endothelial cells were significantly greater in the BMMNC-injected animals (314.8±37.4/0.1 vs. 167.1±11.9/0.1 mm² in controls, P=.02, and 363.3±28.2 cells/0.1 mm² vs. 254.4±28.1 cells/0.1 mm² in controls, P=.03, respectively). The number of blood vessels >50 μm in diameter was significantly increased in the BMMNC group (317.9±54.9 vs. 149.1±6.1, P<.05). The size of the infarct area was smaller in the BMMNC-transplanted group than in the controls (P=.015).

Conclusion

BMMNC transplantation appears to improve angiogenesis and reduce infarct size yet results in no improvement in left ventricular function in a chronically infarcted heart.

Purpose

When radioactive sources are used to treat restenosis, the blood vessels are usually curved. In catheter-based intravascular brachytherapy systems, this curvature introduces dose deviations from the idealized situation used for treatment planning, in which both blood vessels and sources are assumed to be straight. Because of the different depth characteristics of different radionuclides, it is foreseeable that the curvature effects on dosimetry might vary with the different types of radionuclides. In this study, curvature effects on dose distributions along and around a blood vessel were investigated for different gamma and beta emitters.

Materials/Methods

A blood vessel was modeled as a cylinder that could be curved as a circular arc of different degrees. Dose calculations were performed on the cylindrical surfaces of the model vessel for the radioactive sources of ¹⁹²Ir, ¹²⁵I, ¹⁰³Pd, ¹⁸⁸Re, ³²P, and ⁹⁰Y/Sr. The radius of the vessel was assumed to be 1.0, 1.5, 2.0, and 2.5 mm, respectively. A catheter-based radiation delivery system was simulated to consist of a line source with a length of 2 cm. The dose rate at a point in space produced by the radioactive source was computed by integrating the point dose rate kernel of the corresponding radionuclide over the entire radioactive line, which was assumed to curve with the blood vessel along its central axis. Dosimetric calculations were performed for different curvature angles. The curvature effects on the dosimetry were characterized with two quantities, LDU and ADU, where LDU described the longitudinal dose uniformity (LDU) along blood vessels and ADU described the azimuthal dose uniformity (ADU) from the expected delivery dose around blood vessels.

Results

Vessel and source curvatures barely changed the LDU for the gamma emitters (within 2%). The curvature effects on the LDU were relatively larger for the beta emitters (less than 5%). The dose deviations caused by curvature around a blood vessel were more significant. Depending on the radius of the vessel and degree of curvature, the deviation could be as much as 25% for the gamma emitters and 30% for the beta emitters. The curvature effects became larger with the increase of vessel radius and, obviously, with the increase of curvature. There seemed to be no significant differences in the curvature effects among different types of gamma emitters and among different types of beta emitters.

Conclusions

Curvature-induced effects on dose distribution are similar for both the gamma and the beta emitters. The LDU along the vessels does not change significantly with curvature. The dose changes around the vessels are more pronounced and can be as high as 30%.

Purpose

We determined if human aortic endothelial cells (HAEC) enhanced proliferative and angiogenic phenotypes within gas-plasma treated bioresorbable D,L-polylactic acid (D,L-PLA) three-dimensional scaffolds.

Method

6 × 10³ HAEC (N=120) were incubated for 6, 12 or 18 days within either non-treated control or treated scaffolds. Before removing media, unstained wells were observed for apparent cell densities. Quantitative colorimetric WST-1 mitochondrial assays were determined for pooled conditioned media from both HAEC attached to wells and their respective HAEC-containing scaffolds. Fixed HAEC in scaffolds were examined using non-quantitative laser confocal microcopy with FITC-conjugated consensus, Types-I/II or Type-III β-tubulin.

Results

WST-1 indicated that significantly (p<0.05) less mitochondria were on cell culture plates than inside scaffolds but for different reasons. For example, a 12–18 days comparison between WST-1 and β-tubulin indicated that wells decreased because of overgrowth apotosis; whereas, mitochondrial activity inside treated scaffolds decreased with increased tubulogenesis. Observed with consensus and Type-I/II β-tubulin, HAEC-treated scaffolds exhibited increased cell-cell interconnections and angiogenic cords undergoing tubulogenesis to form vessels with central lumens as well as increased Type-III β-tubulin, predominantly in cells of smaller surface areas. Moreover, β-tubulin inside HAEC-treated scaffolds appeared in discrete cytoskeletal and podial regions; yet, β-tubulin for HAEC-control scaffolds was located in more diffuse cytoplasmic regions especially at 18 days.

Conclusions

HAEC-treated scaffolds undergo increased migration, proliferation, β-tubulin expression and quiescent cord formation. HAEC in scaffolds represent a potential model to study mechanisms for vascular cord progression into tubes. WST-1 does not represent accurate cell densities in three-dimensional scaffold matrices.

Background

Hibernating myocardium is defined as a state of persistently impaired myocardial function at rest due to reduced coronary blood flow that can partially or completely be restored to normal if the myocardial oxygen supply/demand relationship is favorably altered. Percutaneous laser revascularization (PMR) is an emerging catheter-based technique that involves creating channels in the myocardium, directly through a percutaneous approach with a laser delivery system, and has been shown to reduce symptoms in patients with severe refractory angina; however, its effect on improving regional wall motion abnormalities in hibernating myocardium has not been clearly established. We sought to determine the effect of PMR using the Eclipse System (Cardiogenesis) on left ventricular function in a porcine model of hibernating myocardium.

Methods

A model of hibernating myocardium was created by placement of an ameroid constrictor in the proximal left anterior descending artery of a 35 kg male Yorkshire pig. The presence of hibernating myocardium was confirmed with dobutamine stress echocardiography (DSE) and defined as severe hypocontractility at rest, with an improvement in systolic wall thickening with low-dose dobutamine in myocardial regions with a subsequent deterioration in function at peak stress (biphasic response). After the demonstration of hibernating myocardium, PMR was performed in the area of hypocontractile function, and the serial echocardiography was performed. The echocardiograms were reviewed by an experienced echocardiologist blinded to the results, and regional wall motion was assessed using the American Society of Echocardiography Wall Motion Score. Six weeks after PMR, the animal was sacrificed and the heart sent for histopathologic studies.

Results

A comparison of the regional wall motion function of the area distal to the ameroid constrictor and in the contralateral wall at baseline, post-ameroid placement, and post-PMR was performed. Hibernating myocardium was demonstrated 4 weeks after ameroid placement by DSE. Coronary angiography demonstrated a discrete 90%stenosis in the proximal LAD at the site of ameroid constrictor placement without evidence of collaterals. Using PMR, 17 bursts were successfully delivered to the anterior wall distal to the ameroid constrictor. Four weeks after PMR, there was improvement in wall motion function in the region distal to the ameroid placement by echocardiography. Histopathologic analysis demonstrated the absence of myocardial infarction in the anterior wall distal to the ameroid constrictor.

Conclusions

The performance of PMR in a porcine model of hibernating myocardium is feasible and is associated with an improvement regional wall motion function after 4 weeks.

Background

Nonionic radiographic contrast media (CM) is reported to be thrombogenic while performing diagnostic or interventional procedures. To avoid thrombosis, heparin is often added to the CM. Bivalirudin, used to replace heparin during percutaneous coronary intervention (PCI), is reported to be associated with reduced bleeding complications. We aimed to evaluate the impact of adding heparin to the CM during PCI in patients (pts) who underwent sirolimus-eluting stent (SES) implantation when bivalirudin was utilized as the sole antithrombotic agent.

Methods

A total of 664 pts with 756 lesions underwent standard PCI with SES for various coronary artery lesions. Pts were treated with either bivalirudin only (the bivalirudin group; 0.75 mg/kg bolus and 1.75 mg/kg/h infusion, n=323 pts) or bivalirudin (same dose) plus low-dose heparin added to the CM (the heparin mix group; mean dose=2101.8±882.5 U, n=341 pts) during PCI. The periprocedural, in-hospital, and 30-day clinical outcomes were compared.

Results

Baseline clinical and angiographic parameters were similar between both groups. Periprocedural, in-hospital, and 1-month clinical outcomes, including thrombotic complications, were similar between the two groups. There was no difference in the periprocedural thrombosis rate between the groups. In the heparin mix group, the overall incidence of hematoma was significantly higher (3.8% vs. 8.5%, P=.01), there was a trend toward higher rates of blood transfusion (2.6% vs. 6.6%, P=.06) and overall vascular complications (0.01% vs. 5.3%, P<.001), including pseudoaneurysm (PSA; 0.0% vs. 2.6%, P=.004), and pts who required surgical repair (0.3% vs. 1.8%, P=.07).

Conclusions

The routine addition of low-dose heparin to CM during contemporary PCI does not add any protection value and is associated with higher rates of bleeding and vascular complications.

Autologous skeletal myoblast transplantation may be used to ameliorate the healing process following myocardium infarct and, hopefully, cardiomyopathies. Despite successful animal experimentation, several issues need to be addressed in clinical settings, i.e., the impact of the delivery route, the extent of short- and long-term survival, and differentiation of the injected skeletal myoblasts. The authors offer some new hypotheses resulting from basic research, i.e., where and when to inject the myogenic cells, whatever their source, how to decrease new myofiber atrophy and improve their regeneration. Although these new hypotheses still need to be tested in humans, they may be decisive for future experimental studies and will lead to making endovascular cell implantation a more effective way to treat ischemic heart disease and failure.

Purpose

In intravascular brachytherapy, either photon or beta emitters are often used in a linear arrangement so that blood vessels of lengths in the range of several centimeters can be treated. With a line source, the dose uniformity and the range of doses that various components of the blood vessels receive depend not only on the type of radionuclides used in the treatment but also on the geometric position of radioactive source relative to the blood vessel walls. The aim of this study is to investigate the dose uniformity around the blood vessel and the effects on the uniformity due to the changes of the off-centering of different photon and beta emitters within the lumen.

Materials and methods

Dose distributions were calculated on a cylindrical blood vessel of various radii. The radioactive sources of ¹⁹²Ir, ¹²⁵I, ¹⁰³Pd, ¹⁸⁸Re, ³²P, and ⁹⁰Y/Sr were studied. All the sources were assumed to be in the form of a line and had a length of 2 cm. The dose rate at a point in space produced by a radioactive source was computed by integrating the point dose rate kernel of the corresponding radionuclide over the 2-cm-long radioactive line. The point dose rate kernel was computed with Monte Carlo simulation of radiation transport. Dosimetric calculations were performed for both concentric and nonconcentric radioactive line source locations. Off-centering effects on the dosimetry were characterized with two newly defined quantities LDU and ADU: LDU describes the longitudinal dose uniformity along blood vessels and ADU describes the azimuthal dose uniformity, i.e., the dose deviation from the expected delivery dose around blood vessels.

Results

The longitudinal dose uniformity did not change significantly with the off-center distance. The azimuthal dose uniformity around the blood vessel deteriorated as the off-center distance increased. The ADU was worse for nonconcentric beta emitters than the photon emitters. For example, if the off-center distance was 1 mm and the radial distance was 1.5 mm, the range of dose around the blood vessel on the central transverse plane (normalized to the corresponding dose under the concentric condition) was from 0.55 to 3.3, 0.56 to 3.3, 0.53 to 3.4, 0.43 to 6.0, 0.38 to 4.3, and 0.31 to 4.7 for ¹⁹²Ir, ¹²⁵I, ¹⁰³Pd, ⁹⁰Y/Sr, ¹⁸⁸Re, and ³²P sources, respectively. However, it appeared that there existed a lower limit of underdosing (about 40% of desired delivery dose) caused by the off-centering for the photon emitters. It was also found that both ADU and LDU became almost independent of source length when the length was longer than or equal to 20 mm.

Conclusions

A generalized formalism for expressing the dose uniformity along and around blood ves