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Fallon A.M.,CorMatrix Cardiovascular Inc. | Goodchild T.T.,Saint Josephs Translational Research Institute | Cox J.L.,Washington University in St. Louis | Matheny R.G.,CorMatrix Cardiovascular Inc.
Journal of Thoracic and Cardiovascular Surgery | Year: 2014

Objectives A novel bioprosthetic tricuspid valve was constructed from an acellular extracellular matrix (ECM) bioscaffold. The valve's mechanical functionality and potential for histologic regeneration was evaluated in an ovine model. Methods The native tricuspid valves of 4 domestic sheep were excised and replaced with bioprosthetic valves constructed from the ECM bioscaffold material shaped into the form of a tube. In vivo function was assessed over time by transthoracic echocardiography. Animals were euthanized at 3, 5, 8, and 12 months after valve implantation, and explanted valves were examined for gross morphology and by qualitative histopathologic analysis. Results All 4 sheep survived until the specified date. Forward flow by echocardiography was normal with trivial to mild regurgitation. Annular morphology and mobility of the leaflets appeared normal with excellent leaflet coaptation. Explanted valves were grossly normal at all time points and showed evidence of progressive tissue remodeling and integration at the host-tissue interface. Histopathologic analysis demonstrated massive host-cell infiltration, structural reorganization of the ECM bioscaffold, elastin generation at the annulus by 3 months, and increased collagen organization and glycosaminoglycan presence in the leaflets by 5 months, with no evidence of foreign body response. Conclusions When implanted in the form of a tubular valve, the acellular ECM bioscaffold demonstrates feasibility as a biomechanically sound bioprosthetic tricuspid valve replacement with evidence of progressive endothelialization and constructive tissue remodeling. © 2014 by The American Association for Thoracic Surgery. Source

Fallon A.,CorMatrix Cardiovascular Inc. | Goodchild T.,Saint Josephs Translational Research Institute | Wang R.,Georgia Institute of Technology | Matheny R.G.,CorMatrix Cardiovascular Inc.
Journal of Surgical Research | Year: 2012

Background: We evaluated the in vitro strength and in vivo arterial-wall response to an extracellular-matrix-based patch material in a sheep model of carotid artery repair. Materials and Methods: A six-ply sheet of acellular, porcine extracellular matrix (ECM) was subjected to in vitro material strength testing and implanted in 15 sheep for 30, 90, and 180 d. Bovine pericardium was used as a control in some animals. In vivo graft patency was assessed by angiography. Explanted grafts were evaluated by histopathology and burst-strength testing. Results: Mean (SD) in vitro suture retention force of the ECM sheet was 14.5 (3.06) N; tensile strength was 29.7 (6.11) N; and probe burst strength was 185 (22.6) N. In vivo, mild stenosis was observed at 30 d for all patches; stenosis was absent at 90 d in the ECM-repaired arteries but not bovine pericardium controls. Pseudoaneurysm was not observed in any animal. Histopathology showed progressive graft degradation, collagen deposition, formation of neocapillaries and fibrocellular neointima, and endothelialization, but no calcification. Mean (SD) burst pressure for unrepaired arteries was 2608 (858) mmHg and 1473 (694) mmHg for ECM-repaired vessels. Mean change in diameter from unloaded state to burst pressure was 29% (9.7) for unrepaired vessels and 24% (13.4) for ECM-repaired vessels. Conclusions: The six-ply ECM sheet can withstand the forces encountered after carotid artery repair. In sheep, it shows evidence of progressive, constructive remodeling as early as 30 d post-implantation with rapid deposition of endothelium. ECM shows promise as a patch material for CEA repair. © 2012 Elsevier Inc. All rights reserved. Source

Forman M.B.,Saint Josephs Translational Research Institute | Sutej P.G.,Arthritis and Rheumatology of Georgia | Jackson E.K.,University of Pittsburgh
Texas Heart Institute Journal | Year: 2011

Elevated catecholamine levels are a well-recognized cause of various types of cardiomyopathy. Causes of catecholamine elevation include tumors, toxins, drugs, emotional stress, and sepsis. Milnacipran is a dual and equipotent inhibitor of norepinephrine and serotonin uptake. It is frequently prescribed as therapy for fibromyalgia, and the drug has a good safety profile. Herein, we report the case of a 42-year-old woman with undefined connective-tissue disease and fibromyalgia who developed a severe and reversible cardiomyopathy while taking recommended doses of milnacipran. The cardiomyopathy was associated with a hyperadrenergic state manifested by tachycardia, hypertension, and elevated plasma catecholamine levels. The discontinuation of milnacipran and the initiation of anti-failure therapy resulted in complete resolution of the cardiomyopathy in 6 months. To our knowledge, this is the first report of milnacipran as a possible cause of catecholamineinduced cardiomyopathy. © 2011 by the Texas Heart ® Institute, Houston. Source

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 182.97K | Year: 2011

DESCRIPTION (provided by applicant): Percutaneous coronary intervention (PCI) is the most frequently employed strategy to revascularize atherosclerotic stenosis of native coronary arteries and saphenous vein grafts. Tissue perfusion is frequently impairedfollowing PCI, particularly in patients with ST segment elevation myocardial infarction (STEMI). This results in the no-reflow phenomenon which is an important predictor of mortality. Adenosine is an endogenous nucleoside that attenuates many of the mechanisms responsible for the no-reflow phenomenon. Experimental and clinical studies have confirmed adenosine's efficacy in enhancing myocardial salvage and improving microvascular blood flow. Adensoine's full therapeutic potential is compromised due to its ultra short half life requiring large doses to obtain adequate blood levels at the target organ. Since the guidewire is the first PCI device that perturbs the vascular bed, we have developed the concept of elution of adenosine continuously via an adenosine-polymer-coated guidewire. We have developed a number of unique physiologic polymers in which adenosine can be covalently incorporated and placed on a guidewire. We tested out first generation polymers (LDI-glycerol and LDI-adenosine) in a small animal model and verified that it resulted in a substantial increase in blood flow. However in a large animal model the kinetic profile was too rapid for a typical interventional procedure (~45 mins). We have subsequently developed two new polymers, LDI- cysteineand LDI-PEG. Prior to initiating large animal studies in a Phase 2 study it is imperative we optimize the polymer structure, guidewire-coating methodology and kinetic release profile. We therefore propose the following studies with the new polymers to identify an ideal product. First we will develop and characterize the structure of the polymers and permutations thereof and evaluate numerous coating methodologies to optimize release kinetic profile. Second we will evaluate adenosine elution utilizing a temperature controlled recirculating water bath system and measure adenosine release serially with HPLC. Third we will determine if the selected polymer is safe for clinical use by employing NAMSA- based screening tests for cytotoxicity, pyrogenicity, hemolysis, and sensitization. Finally we will evaluate the stability and durability of the polymer with glass transition temperature experiments and by passing coated wires through simulated lesions. If the anti-no-reflow wire is shown to be effective in improving outcomes after interventional procedures it will represent a major advance in the treatment of patients with coronary artery disease undergoing PCI. This will have important societal benefits due to the large number of interventional procedures performed in the US each year for coronary artery disease. PUBLIC HEALTH RELEVANCE: The improved outcomes that may potentially occur with the device would have important societal benefits due to the large number of interventional procedures performed inthe US each year for atherosclerotic disease.

Saint Josephs Translational Research Institute | Date: 2011-04-19

The present invention provides an access device for surgery. The access device includes a guide member and a head member. The guide member and head member define a channel configured to receive and guide a sterile flexible scope with a working channel. The guide member and head member cooperate to extend through a small opening of 2 cm or less to access tissue structures. The head member may include surfaces to separate a pericardium from a surface of the heart, stabilize a beating heart and, with the endoscope, provide visibility for the implantation of a therapeutic such as stem cells to the surface of the heart with improved safety and accuracy. Ranges of other diagnostic, application of therapeutics or biologics, and observational applications may be facilitated by the access device, such as TMR, ablation, echo-probe diagnostics, LAA isolation, observation of the same procedures, etc.

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