Search

NO-releasing diazeniumdiolated derivatives of poly(acrylonitrile) (PAN) and a variety of related materials are prepared that can form the basis of NO-releasing textiles, rubbers and plastics. These diazeniumdiolated acrylonitrile-based polymers are stable at room temperatures for many months and thus represent a broad class of commercially viable materials to be developed as NO donors.

Background: Late failure of prosthetic vascular bypass grafting using expanded polytetrafluoroethylene (ePTFE) is secondary to the development of neointimal hyperplasia, most commonly at the distal anastomosis. To develop therapies that can improve upon current prosthetic vascular bypass grafting, a large animal model of prosthetic bypass grafting that results in reproducible neointimal hyperplasia is necessary. Methods: We performed bilateral end-to-side carotid artery bypasses with 6 mm ePTFE in a porcine model (n = 11). We studied graft patency using magnetic resonance angiography (MRA, 3 wk), duplex ultrasonography (4 wk), and digital-subtraction contrast angiography (4 wk). Animals were sacrificed at 4 wk and morphometric analysis was performed. Results: Of the 11 animals that underwent surgery, one pig died from respiratory compromise; of the remaining 10, graft patency was 90% at 4 wk. Peak systolic and end diastolic velocities were established for this model using ultrasonography. MRA, ultrasonography, and angiography confirmed graft patency and were complimentary tools to evaluate the grafts. Development of neointimal hyperplasia was reproducible at 4 wk in both the proximal and distal anastomoses (2.5 to 3 mm2) of the ePTFE bypass grafts. Conclusion: We developed a reproducible porcine ePTFE carotid artery bypass model for studying neointimal hyperplasia. Not only does this model allow for the manipulation and evaluation of potential therapies, but patency and neointimal hyperplasia can be easily evaluated by traditional means, such as MRA, ultrasonography, and angiography. This preclinical model is ideal for evaluation of novel therapies in vivo designed to inhibit neointimal hyperplasia following arterial reconstruction with prosthetic bypass grafting. [Copyright &y& Elsevier]

Background: Injury to and dysfunction of the endothelium can compromise the patency of coronary arteries and lead to impaired perfusion of the heart. Such injury can occur after the application of an intravascular shunt and/or a snare to a coronary artery during bypass surgery. In this study, multiphoton microscopy was used to assess the integrity of endothelium in porcine coronary arteries subjected to shunting and snaring during off-pump coronary artery bypass grafting (OPCAB). Materials and methods: In open chest porcine, the left anterior descending artery was manipulated in different regions using snare and shunt to simulate OPCAB. Sections of left anterior descending artery were labeled with fluorescent dyes to evaluate the viability of the endothelium. The structural integrity of the endothelium was evaluated by calcein- and ethidium homodimer-mediated fluorescence. Endothelial functional viability was assessed by measuring cellular esterase activity, calcium mobilization, and endothelial nitric oxide synthase-mediated generation of nitric oxide using fluorescence dyes and multiphoton microscopy. Results: Substantial endothelial damage was observed in shunted region of the coronary arteries. In contrast, endothelium remained structurally viable in regions that were snared, similar to control regions of the coronary arteries that were not manipulated. Esterase activity, calcium mobilization, and nitric oxide generation was greater in the control and snared regions of the coronary arteries in comparison to the shunted region. Conclusions: The use of intracoronary shunts led to structural damage and attenuation of endothelial function in porcine coronary arteries, whereas snared vessels maintained their viability and integrity, similar to the control sections. The routine use of shunts in OPCABG may lead to endothelial damage and possibly to long-term graft failure. [Copyright &y& Elsevier]

Background: Injury to and dysfunction of the endothelium can compromise the patency of coronary arteries and lead to impaired perfusion of the heart. Such injury can occur after the application of an intravascular shunt and/or a snare to a coronary artery during bypass surgery. In this study, multiphoton microscopy was used to assess the integrity of endothelium in porcine coronary arteries subjected to shunting and snaring during off-pump coronary artery bypass grafting (OPCAB)., Materials and Methods: In open chest porcine, the left anterior descending artery was manipulated in different regions using snare and shunt to simulate OPCAB. Sections of left anterior descending artery were labeled with fluorescent dyes to evaluate the viability of the endothelium. The structural integrity of the endothelium was evaluated by calcein- and ethidium homodimer-mediated fluorescence. Endothelial functional viability was assessed by measuring cellular esterase activity, calcium mobilization, and endothelial nitric oxide synthase-mediated generation of nitric oxide using fluorescence dyes and multiphoton microscopy., Results: Substantial endothelial damage was observed in shunted region of the coronary arteries. In contrast, endothelium remained structurally viable in regions that were snared, similar to control regions of the coronary arteries that were not manipulated. Esterase activity, calcium mobilization, and nitric oxide generation was greater in the control and snared regions of the coronary arteries in comparison to the shunted region., Conclusions: The use of intracoronary shunts led to structural damage and attenuation of endothelial function in porcine coronary arteries, whereas snared vessels maintained their viability and integrity, similar to the control sections. The routine use of shunts in OPCABG may lead to endothelial damage and possibly to long-term graft failure.