Cell transplantation has recently emerged as a novel therapy for ischemic heart disease. The presented study investigated the effect of intramyocardial transfer of human endothelial progenitor cells (EPCs) and stromal-cell derived factor-1alpha (SDF-1alpha) on left ventricular function in a chronic setting after myocardial infarction in cyclosporine treated rats. BrdU-labeled EPCs (10(6)), 10 microg SDF-1alpha, EPCs+SDF-1alpha or placebo medium were injected directly into the border infarct zone 4 weeks after acute myocardial infarction. Eight weeks after transplantation, echocardiography identified significantly improved fractional shortening after EPC or EPCs+SDF-1alpha injection as compared with injection of placebo medium. Investigating isolated hearts revealed a significant increase in left ventricular developing pressure after transplantation of SDF-1alpha or EPCs+SDF-1alpha. Furthermore, coronary flow rates were significantly elevated, especially after transplantation of EPCs+SDF-1alpha (under catecholamine stress 24.2 +/- 1.55 ml/min vs. 13.1 +/- 1 ml/min in the control) correlating with increased density of CD31+ vessel structures in the EPC as well as EPCs+SDF-1alpha groups, thus defining a higher rate of neovascularization. Notably, SDF-1alpha injected hearts showed only a trend towards improvement in coronary flow. BrdU+ signals were detected in infarct areas, partially integrating into vascular networks. The rate of apoptotic cells as well as the amount of inflammatory cells was significantly elevated in the placebo control group. In conclusion, transplantation of EPCs as well as EPCs+SDF-1alpha associated with improvement in cardiac function after infarction, which was attributable to enhanced neovascularization and decreased inflammation. These results imply a combined benefit of EPCs+SDF-1alpha in the treatment of myocardial infarction.
The respiratory component of heart rate variability (respiratory sinus arrhythmia, RSA) has been associated with improved pulmonary gas exchange efficiency in humans via the apparent clustering and scattering of heart beats in time with the inspiratory and expiratory phases of alveolar ventilation, respectively. However, since human RSA causes only marginal redistribution of heart beats to inspiration, we tested the hypothesis that any association between RSA amplitude and pulmonary gas exchange efficiency may be indirect. In 11 patients with fixed-rate cardiac pacemakers and 10 healthy control subjects, we recorded R-R intervals, respiratory flow, end-tidal gas tension and the ventilatory equivalents for carbon dioxide (V E /V CO 2 ) and oxygen (V E /V O 2 ) during 'fast' (0.25 Hz) and 'slow' paced breathing (0.10 Hz). Mean heart rate, mean arterial blood pressure, mean arterial pressure fluctuations, tidal volume, endtidal CO 2 ,V E /V CO 2 andV E /V O 2 were similar between pacemaker and control groups in both the fast and slow breathing conditions. Although pacemaker patients had no RSA and slow breathing was associated with a 2.5-fold RSA amplitude increase in control subjects (39 ± 21 versus 97 ± 45 ms, P < 0.001), comparableV E /V CO 2 (main effect for breathing frequency, F(1,19) = 76.54, P < 0.001) andV E /V O 2 reductions (main effect for breathing frequency, F(1,19) = 23.90, P < 0.001) were observed for both cohorts during slow breathing. In addition, the degree ofV E /V CO 2 (r = −0.36, P = 0.32) andV E /V O 2 reductions (r = −0.29, P = 0.43) from fast to slow breathing were not correlated to the degree of associated RSA amplitude enhancements in control subjects. These findings suggest that the association between RSA amplitude and pulmonary gas exchange efficiency during variable-frequency paced breathing observed in prior human work is not contingent on RSA being present. Therefore, whether RSA serves an intrinsic physiological function in optimizing pulmonary gas exchange efficiency in humans requires further experimental validation.
Modeling driven by small-angle X-ray scattering (SAXS) combines low-resolution data with computational modeling to predict the structure of biomolecular assemblies. A new protocol, ATTRACT-SAXS, has been developed and tested on a large protein-protein docking benchmark with simulated SAXS data. For 88% of cases, high-quality solutions were generated using SAXS data alone without a physiochemical force field (interface-RMSD ≦ 2 Å or ligand-RMSD ≦ 5 Å; and more than 30% native contacts). ATTRACT-SAXS gave significant improvements compared with previous approaches that filter by SAXS a posteriori. When combining SAXS and interface properties for scoring, the protocol placed high-quality models in 70% of cases among the top-ranked 100 clusters. ATTRACT-SAXS also gave good results when tested on experimental data if the native complex structure was compatible with the SAXS profile. Our results show that, in principle, SAXS on its own can contain enough information to generate high-quality models of protein-protein complexes.
As a novel and promising therapeutic strategy for heart failure, the application of different cell types is the subject of increasing research interest. In this study we investigated the effect of several cell types and microspheres (uniform polystyrene microspheres, 10 microm diameter) transplanted 4 weeks after induction of myocardial infarction in a rat model. Eight weeks after intramyocardial application of fibroblasts and microspheres, left ventricular function was significantly improved as demonstrated by isolated heart studies (Langendorff) and echocardiographic findings (LVDP fibroblasts 129 +/- 32.9 mmHg, LVDP microspheres 119.2 +/- 24.1 mmHg, fractional shortening (FS) microspheres 38.9 +/- 4.6%, FS fibroblasts 36.84 +/- 6.05%) in contrast to injection of macrophages or medium alone (LVDP medium 67 +/- 22.6 mmHg, LVDP macrophages 75.9 +/- 24.8 mmHg, FS macrophages 29.16 +/- 8.7%, FS medium 27.2 +/- 7.2%, P < 0.05). Signals of Bromodesoxy-Uridine (BrdU) labeled transplanted fibroblasts were detected in infarcted areas. Microspheres were recorded abundantly by autofluorescence. Significantly more apoptotic cells were observed in infarcted areas of macrophage (328.6 +/- 37.4 cells/mm(2)) and medium (338.7 +/- 16.5 cells/mm(2); P < 0.05) treated hearts compared to microsphere (233.2 +/- 16.8 cells/mm(2)) and fibroblast (232.2 +/- 19.1 cells/mm(2)) injected hearts. Neovascularization, as reflected by the density of CD 31 positive vessels in the infracted area, did not differ between the four groups studied. The increased number of macrophages in infarcted areas after fibroblast and microsphere injection (fibroblasts 94.7 +/- 7.1 cells/mm(2), microspheres 82.2 +/- 3.0 cells/mm(2), macrophages 56.02 +/- 9.93 cells/mm(2), medium 46.35 +/- 9.03 cells/mm(2), P < 0.05) suggests that the underlying mechanism of augmented left ventricular function might be based on inflammatory processes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.