Methods and compositions for vein harvest and autografting
Inventors
Brophy, Colleen M. • Komalavilas, Padmini • Cheung-Flynn, Joyce • Hocking, Kyle M. • Eagle, Susan S.
Assignees
US Department of Veterans Affairs • Vanderbilt University
Publication Number
US-8691556-B2
Publication Date
2014-04-08
Expiration Date
2030-12-08
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Abstract
The leading cause of graft failure is the subsequent development of intimal hyperplasia, which represents a response to injury that is thought to involve smooth muscle proliferation, migration, phenotypic modulation, and extracellular matrix (ECM) deposition. Surgical techniques typically employed for vein harvest—stretching the vein, placing the vein in low pH, solutions, and the use of toxic surgical skin markers—are shown here to cause injury. The invention therefore provides for non-toxic surgical markers than also protect against stretch-induced loss of functional viability, along with other additives. Devices and compositions for reducing physical stress or protecting from the effects flowing therefrom, also are provided.
Core Innovation
The invention provides methods and compositions for treating vein explants prior to transplant to preserve and restore their functional viability. It addresses the problem that surgical techniques typically used during vein harvest, such as stretching the vein, placing it in low pH solutions, and using toxic surgical skin markers, cause injury to the vein leading to loss of smooth muscle and endothelial function. This injury can contribute to intimal hyperplasia, a major cause of graft failure characterized by smooth muscle proliferation, migration, and extracellular matrix deposition.
The invention offers buffered solutions at physiological pH (7.0-7.6) containing P2X7 receptor antagonists such as erioglaucine/Blue Dye #1 or brilliant blue G, which stabilize the vein explant and preserve functional viability. The solutions may include additional additives such as heparin, anti-contractile agents, antioxidants, oligosaccharides, colloid agents, anti-inflammatory agents, endothelial function preservatives, metabolic regulators, hydrogels, inhibitors of heat shock protein 27, regulators of HSP20, and inhibitors of MAPKAP kinase 2. Furthermore, the invention provides devices to reduce physical stress on the vein, including pressure limiting "pop-off" valves to prevent excessive intraluminal pressures during manual distension, and non-toxic surgical markers containing P2X7 receptor antagonists for vein marking.
Claims Coverage
The patent includes one primary independent method claim covering the treatment of vein explants prior to transplant and related features.
Method of stabilizing vein explants using buffered solutions with P2X7 receptor antagonists
A method comprising providing a vein explant, stabilizing the vein explant in a buffered solution at pH 7.0-7.6 that includes a P2X7 receptor antagonist to produce a stabilized vein explant, and preserving its functional viability.
Use of specific P2X7 receptor antagonists and solution components
Including heparin and P2X7 receptor antagonists such as erioglaucine/Blue Dye #1 or brilliant blue G within buffered solutions composed of phosphate buffered saline, MOPS, Hepes, Pipes, acetate, or Plasmalyte, optionally with additives like anti-contractile agents, antioxidants, oligosaccharides, colloids, anti-inflammatory agents, endothelial function preservatives, metabolic regulators, hydrogels, inhibitors of heat shock proteins, regulators of HSP20, or MAPKAP kinase 2 inhibitors.
Marking vein explants with non-alcohol based markers containing P2X7 receptor antagonists
Marking the vein explant with non-alcohol based markers such as erioglaucine/Blue Dye #1 or brilliant blue G that act as P2X7 receptor antagonists to protect or restore functional viability.
Limiting flushing pressures during vein explant preparation
Flushing the lumen of the vein explant such that internal flushing pressures do not exceed 200 mm Hg to prevent injury and preserve functional viability.
The claims cover a comprehensive method for preserving and restoring vein explant functionality involving buffered solutions with P2X7 receptor antagonists and other protective additives, non-toxic marking compositions, and devices controlling physical stress such as pressure during vein preparation.
Stated Advantages
The method preserves functional viability of vein explants, maintaining smooth muscle contractility and endothelial-dependent relaxation.
Use of non-toxic surgical markers containing P2X7 receptor antagonists avoids injury caused by conventional toxic markers.
Pressure limiting devices prevent excessive intraluminal pressures during vein manual distension, thus protecting conduit function.
Buffered solutions at physiological pH prevent the deleterious effects associated with acidic pH solutions typically used in harvest.
Inclusion of various protective additives addresses injury, spasm, oxidative damage, inflammation, and endothelial dysfunction.
Documented Applications
Use in surgical harvesting, treatment, preservation, and transplantation of autologous vein grafts for coronary and peripheral arterial bypass procedures.
Prevention of intimal hyperplasia leading to vein graft failure following vein harvest and implantation.
Medical devices and methods for maintaining vein explant viability during handling, including marking pens, vein storage kits, and flushing devices with pressure control.
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