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1.  An Electrically Coupled Tissue Engineered Cardiomyocyte Scaffold Improves Cardiac Function in Rats with Chronic Heart Failure 
Varying strategies are currently being evaluated to develop tissue-engineered constructs for the treatment of ischemic heart disease. This study examines an angiogenic and biodegradable cardiac construct seeded with neonatal cardiomyocytes for the treatment of chronic heart failure (CHF).
We evaluated a neonatal cardiomyocyte (NCM)-seeded three-dimensional fibroblast construct (3DFC) in vitro for the presence of functional gap junctions and the potential of the NCM-3DFC to restore left ventricular (LV) function in an in vivo rat model of CHF at 3 weeks after permanent left coronary artery ligation.
The NCM-3DFC demonstrated extensive cell-to-cell connectivity following dye injection. At 5 days in culture, the patch contracted spontaneously in a rhythmic and directional fashion, at 43±3 beats/min with a mean displacement of 1.3±0.3 mm and contraction velocity of 0.8±0.2 mm/sec. The seeded patch could be electrically paced at near physiological rates (270±30 beats/min) while maintaining coordinated, directional contractions. Three weeks after implantation, the NCM-3DFC improved LV function by increasing (p<0.05) ejection fraction 26%, cardiac index 33%, dP/dt(+) 25%, dP/dt(−) 23%, and peak developed pressure (PDP) 30%, while decreasing (p<0.05) LV end diastolic pressure 38% and the time constant of relaxation (Tau) 16%. Eighteen weeks post implantation, the NCM-3DFC improved LV function by increasing (p<0.05) ejection fraction 54%, mean arterial pressure 20%, dP/dt(+) 16%, dP/dt(−) 34% and PDP 39%.
This study demonstrates that a multicellular, electromechanically organized, cardiomyocyte scaffold, constructed in vitro by seeding NCM onto 3DFC, can improve LV function long-term when implanted in rats with CHF.
PMCID: PMC3966928  PMID: 24560982
Chronic heart failure; ventricular function ventricles; ejection fraction; cardiomyocytes; cell therapy
2.  Utility of nuclear stress imaging for detecting coronary artery bypass graft disease 
The value of Single Photon Emission Computed Tomography stress myocardial perfusion imaging (SPECT-MPI) for detecting graft disease after coronary artery bypass surgery (CABG) has not been studied prospectively in an unselected cohort.
Radial Artery Versus Saphenous Vein Graft Study is a Veterans Affairs Cooperative Study to determine graft patency rates after CABG surgery. Seventy-nine participants agreed to SPECT-MPI within 24 hours of their coronary angiogram, one-year after CABG. The choice of the stress protocol was made at the discretion of the nuclear radiologist and was either a symptom-limited exercise test (n = 68) or an adenosine infusion (n = 11). The SPECT-MPI results were interpreted independent of the angiographic results and estimates of sensitivity, specificity and accuracy were based on the prediction of a graft stenosis of ≥70% on coronary angiogram.
A significant stenosis was present in 38 (48%) of 79 patients and 56 (22%) of 251 grafts. In those stress tests with an optimal exercise heart rate response (>80% maximum predicted heart rate) (n = 26) sensitivity, specificity and accuracy of SPECT-MPI for predicting the graft stenosis was 77%, 69% and 73% respectively. With adenosine (n = 11) it was 75%, 57% and 64%, respectively. Among participants with a suboptimal exercise heart rate response, the sensitivity of SPECT-MPI for predicting a graft stenosis was <50%. The accuracy of SPECT-MPI for detecting graft disease did not vary significantly with ischemic territory.
Under optimal stress conditions, SPECT-MPI has a good sensitivity and accuracy for detecting graft disease in an unselected patient population 1 year post-CABG.
PMCID: PMC3469356  PMID: 22862805
Coronary artery bypass grafts; CABG; Coronary artery imaging; Cardiac catheterization/intervention
3.  Successful coronary angiography with adequate image acquisition using a combination of gadolinium and a power injector in a patient with severe iodine contrast allergy 
A history of severe allergic reaction to iodine contrast leading to anaphylactic shock presents a dilemma in patients requiring cardiac catheterization. As an alternative, gadolinium has been an interesting and potentially useful agent. However, gadolinium produces poor image quality and has been associated with significant arrhythmias in small case series. Furthermore, there is no consensus about the maximal allowable dose that can be administered to a patient. In the present report, a successful combination of gadolinium contrast with a power injector that produced adequate image quality in a patient with severe allergy to iodine contrast is described. The case was complicated by the occurrence of ventricular fibrillation when damping occurred during injection of contrast into the right coronary artery. This complication has been reported previously with intracoronary gadolinium injection. The report is followed by a brief literature review.
PMCID: PMC3383362  PMID: 23204895
Angiography; Complication; Gadolinium use; Iodine contrast allergy; PCI complication; Percutaneous coronary intervention; Stenting; Ventricular fibrillation
4.  Toxicity Assessment of Titanium (IV) Oxide Nanoparticles Using Daphnia magna (Water Flea) 
Titanium dioxide (TiO2), a common nanoparticle widely used in industrial production, is one of nano-sized materials. The purpose of this study was to determine the acute and chronic toxicity of TiO2 using different size and various concentrations on Daphnia magna.
In the acute toxicity test, four concentrations (0, 0.5, 4, and 8 mM) for TiO2 with 250 or 500 nm and five concentrations (0, 0.25, 0.5, 0.75, and 1 mM) for TiO2 with 21 nm were selected to analyze the toxic effect to three groups of ten daphnia neonates over 96 hours. In addition, to better understand their toxicity, chronic toxicity was examined over 21 days using 0, 1, and 10 mM for each type of TiO2.
Our results showed that all organisms died before the reproduction time at a concentration of 10 mM of TiO2. In addition, the exposure of anatase (21 nm) particles were more toxic to D. magna, comparing with that of anatase (250 nm) and rutile (500 nm) particles.
This study indicated that TiO2 had adverse impacts on the survival, growth and reproduction of D. magna after the 21days exposure. In addition, the number of test organisms that were able to reproduce neonates gradually were reduced as the size of TiO2 tested was decreased.
PMCID: PMC3214988  PMID: 22125763
Titanium dioxide; Daphnia magna; Size-dependent toxicity; Acute toxicity; Chronic toxicity
5.  Implantation of a Three-Dimensional Fibroblast Matrix Improves Left Ventricular Function and Blood Flow After Acute Myocardial Infarction 
Cell transplantation  2009;18(3):283-295.
This study was designed to determine if a viable biodegradable three-dimensional fibroblast construct (3DFC) patch implanted on the left ventricle after myocardial infarction (MI) improves left ventricular (LV) function and blood flow. We ligated the left coronary artery of adult male Sprague-Dawley rats and implanted the 3DFC at the time of the infarct. Three weeks after MI, the 3DFC improved LV systolic function by increasing (p < 0.05) ejection fraction (37 ± 3% to 62 ± 5%), increasing regional systolic displacement of the infarcted wall (0.04 ± 0.02 to 0.11 ± 0.03 cm), and shifting the passive LV diastolic pressure volume relationship toward the pressure axis. The 3FDC improved LV remodeling by decreasing (p < 0.05) LV end-systolic and end-diastolic diameters with no change in LV systolic pressure. The 3DFC did not change LV end-diastolic pressure (LV EDP; 25 ± 2 vs. 23 ± 2 mmHg) but the addition of captopril (2mg/L drinking water) lowered (p < 0.05) LV EDP to 12.9 ± 2.5 mmHg and shifted the pressure–volume relationship toward the pressure axis and decreased (p < 0.05) the LV operating end-diastolic volume from 0.49 ± 0.02 to 0.34 ± 0.03 ml. The 3DFC increased myocardial blood flow to the infarcted anterior wall after MI over threefold (p < 0.05). This biodegradable 3DFC patch improves LV function and myocardial blood flow 3 weeks after MI. This is a potentially new approach to cell-based therapy for heart failure after MI.
PMCID: PMC2739416  PMID: 19558777
Acute myocardial infarct; Fibroblasts; Growth factors; Angiogenesis; Extracellular matrix; Bioabsorbable scaffold

Results 1-5 (5)