1 Division of Cardiothoracic Surgery, Department of Surgery, and 2 Department of Physiology, University of Pennsylvania School of Medicine; and 3 Institute for Medicine and Engineering, School of ...Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania
Submitted 26 September 2005
; accepted in final form 30 January 2006
Cellular therapy for myocardial injury has improved ventricular function in both animal and clinical studies, though the mechanism of benefit is unclear. This study was undertaken to examine the effects of cellular injection after infarction on myocardial elasticity. Coronary artery ligation of Lewis rats was followed by direct injection of human mesenchymal stem cells (MSCs) into the acutely ischemic myocardium. Two weeks postinfarct, myocardial elasticity was mapped by atomic force microscopy. MSC-injected hearts near the infarct region were twofold stiffer than myocardium from noninfarcted animals but softer than myocardium from vehicle-treated infarcted animals. After 8 wk, the following variables were evaluated: MSC engraftment and left ventricular geometry by histological methods, cardiac function with a pressure-volume conductance catheter, myocardial fibrosis by Masson Trichrome staining, vascularity by immunohistochemistry, and apoptosis by TdT-mediated dUTP nick-end labeling assay. The human cells engrafted and expressed a cardiomyocyte protein but stopped short of full differentiation and did not stimulate significant angiogenesis. MSC-injected hearts showed significantly less fibrosis than controls, as well as less left ventricular dilation, reduced apoptosis, increased myocardial thickness, and preservation of systolic and diastolic cardiac function. In summary, MSC injection after myocardial infarction did not regenerate contracting cardiomyocytes but reduced the stiffness of the subsequent scar and attenuated postinfarction remodeling, preserving some cardiac function. Improving scarred heart muscle compliance could be a functional benefit of cellular cardiomyoplasty.
cell transplantation; myocardial remodeling
Address for reprint requests and other correspondence: H. L. Sweeney, Dept. of Physiology, Univ. of Pennsylvania School of Medicine, A700 Richards Bldg., 3700 Hamilton Walk, Philadelphia, PA 19104-6085 (e-mail: lsweeney{at}mail.med.upenn.edu )
Time-locked sequences of neural activity can be found throughout the vertebrate forebrain in various species and behavioral contexts. From "time cells" in the hippocampus of rodents to cortical ...activity controlling movement, temporal sequence generation is integral to many forms of learned behavior. However, the mechanisms underlying sequence generation are not well known. Here, we describe a spatial and temporal organization of the songbird premotor cortical microcircuit that supports sparse sequences of neural activity. Multi-channel electrophysiology and calcium imaging reveal that neural activity in premotor cortex is correlated with a length scale of 100 µm. Within this length scale, basal-ganglia-projecting excitatory neurons, on average, fire at a specific phase of a local 30 Hz network rhythm. These results show that premotor cortical activity is inhomogeneous in time and space, and that a mesoscopic dynamical pattern underlies the generation of the neural sequences controlling song.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely ...heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying peripheral interfacing technologies. Here, we present a microscale implantable device - the nanoclip - for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high signal-to-noise ratio recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation within the confines of the small device can achieve multi-dimensional control of a small nerve. These results highlight the potential of new microscale design and fabrication techniques for realizing viable devices for long-term peripheral interfacing.
Apelin has been shown ex vivo to be a potent cardiac inotrope. This study was undertaken to evaluate the in vivo effects of apelin on cardiac function in native and ischemic cardiomyopathic rat ...hearts using a novel combination of a perivascular flow probe and a conductance catheter.
Native rats (n =32) and rats in heart failure 6 weeks after left anterior descending coronary artery ligation (n =22) underwent median sternotomy with placement of a perivascular flow probe around the ascending aorta and a pressure volume conductance catheter into the left ventricle. Compared with sham-operated rats, the ligated rats had significantly decreased baseline Pmax and max dP/dt. Continuous infusion of apelin at a rate of 0.01 microg/min for 20 minutes significantly increased Pmax and max dP/dt compared with infusion of vehicle alone in both native and failing hearts. Apelin infusion increased cardiac contractility, indicated by a significant increase in stroke volume (SV) without a change in left ventricular end diastolic volume (102+/-16% change from initial SV versus 26+/-20% for native animals, and 110+/-30% versus 26+/-11% for ligated animals), as well as an increase in preload recruitable stroke work (180+/-24 mm Hg versus 107+/-9 mm Hg for native animals).
The present study is the first to show that apelin has positive inotropic effects in vivo in both normal rat hearts and rat hearts in failure after myocardial infarction. Apelin may have use as an acute inotropic agent in patients with ischemic heart failure.
This report describes a 3D microelectrode array integrated on a thin-film flexible cable for neural recording in small animals. The fabrication process combines traditional silicon thin-film ...processing techniques and direct laser writing of 3D structures at micron resolution via two-photon lithography. Direct laser-writing of 3D-printed electrodes has been described before, but this report is the first to provide a method for producing high-aspect-ratio structures. One prototype, a 16-channel array with 300 µm pitch, demonstrates successful electrophysiological signal capture from bird and mouse brains. Additional devices include 90 µm pitch arrays, biomimetic mosquito needles that penetrate through the dura of birds, and porous electrodes with enhanced surface area. The rapid 3D printing and wafer-scale methods described here will enable efficient device fabrication and new studies examining the relationship between electrode geometry and electrode performance. Applications include small animal models, nerve interfaces, retinal implants, and other devices requiring compact, high-density 3D electrodes.
The mission of the American Heart Association/American Stroke Association includes increasing access to high-quality, evidence-based care that improves patient outcomes such as health-related quality ...of life and is consistent with the patients’ values, preferences, and goals. Awareness of and access to palliative care interventions align with the American Heart Association/American Stroke Association mission. The purposes of this policy statement are to provide background on the importance of palliative care as it pertains to patients with advanced cardiovascular disease and stroke and their families and to make recommendations for policy decisions. Palliative care, defined as patient- and family-centered care that optimizes health-related quality of life by anticipating, preventing, and treating suffering, should be integrated into the care of all patients with advanced cardiovascular disease and stroke early in the disease trajectory. Palliative care focuses on communication, shared decision making about treatment options, advance care planning, and attention to physical, emotional, spiritual, and psychological distress with inclusion of the patient’s family and care system. Our policy recommendations address the followingreimbursement for comprehensive delivery of palliative care services for patients with advanced cardiovascular disease and stroke; strong payer-provider relationships that involve data sharing to identify patients in need of palliative care, identification of better care and payment models, and establishment of quality standards and outcome measurements; healthcare system policies for the provision of comprehensive palliative care services during hospitalization, including goals of care, treatment decisions, needs of family caregivers, and transition to other care settings; and health professional education in palliative care as part of licensure requirements.
Objective. Chronic neural recording in behaving animals is an essential method for studies of neural circuit function. However, stable recordings from small, densely packed neurons remains ...challenging, particularly over time-scales relevant for learning. Approach. We describe an assembly method for a 16-channel electrode array consisting of carbon fibers (<5 µm diameter) individually insulated with Parylene-C and fire-sharpened. The diameter of the array is approximately 26 µm along the full extent of the implant. Main results. Carbon fiber arrays were tested in HVC (used as a proper name), a song motor nucleus, of singing zebra finches where individual neurons discharge with temporally precise patterns. Previous reports of activity in this population of neurons have required the use of high impedance electrodes on movable microdrives. Here, the carbon fiber electrodes provided stable multi-unit recordings over time-scales of months. Spike-sorting indicated that the multi-unit signals were dominated by one, or a small number of cells. Stable firing patterns during singing confirmed the stability of these clusters over time-scales of months. In addition, from a total of 10 surgeries, 16 projection neurons were found. This cell type is characterized by sparse stereotyped firing patterns, providing unambiguous confirmation of single cell recordings. Significance. Carbon fiber electrode bundles may provide a scalable solution for long-term neural recordings of densely packed neurons.
•Quartic force fields of the highest level provide rotational constants to within, on average, 34 MHz of experiment.•Tetraatomic species with low anharmonicities can be within 20 MHz.•These same ...methods provide vibrational frequencies to within, on average, 5.8 cm−1.
The CcCR quartic force field (QFF) methodology is capable of computing B0 and C0 rotational constants to within 35 MHz (0.14%) of experiment for triatomic and larger molecules with at least two heavy atoms. Additionally, the same constants for molecules with four or more atoms agree to within 20 MHz (0.12%) of experiment for the current test set. This work also supports previous claims that the same QFF methodology can produce fundamental vibrational frequencies with a deviation less than 5.7 cm−1 from experiment. Consequently, this approach of augmenting complete basis set extrapolated energies with treatments of core electron correlation and scalar relativity produces some of the most accurate rovibrational spectroscopic data available.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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