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Does a Preservation Solution for Vascular Grafts Matter? PowerPoint Presentation
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Does a Preservation Solution for Vascular Grafts Matter?

Does a Preservation Solution for Vascular Grafts Matter?

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Does a Preservation Solution for Vascular Grafts Matter?

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  1. Does a Preservation Solution for Vascular Grafts Matter?

  2. CABG has the most solid evidence from recent RCTs supporting its role in revascularization for stable CAD(Ferguson, Jr., Future Cardiol 2014) • In the SYNTAX Trial (1800 patients with 3-vessel or left main CAD randomized to CABG or PCI (in a 1:1 ratio), rates of MACCE at 12 months were significantly higher in the PCI group (17.8%, vs. 12.4%, P = 0.002) (Serruys NEJM 2009). • 5-year results of SYNTAX in patients with 3-vessel CAD concluded that CABG should remain the standard of care; it significantly lower rates of death, MI, and repeat revascularization, while stroke rates were similar(Head, European Heart J 2014). • PCI impairs endothelial function; itonly treats ‘SUITABLE’ localized proximal ‘culprit’ lesions but has NO PROPHYLACTIC BENEFIT against new disease.

  3. Despite the fact that the efficacy of CABG is limited by SVG failure, this continues to be the most used vascular graft (Harskamp, Ann Surg 2013). In vitro data suggest that intraoperative preservation solutions may influence endothelial function and SVG failure after CABG. Data from the PREVENT IV study showed thatCABG pts. whose SVG were preserved in a buffered solution like DuraGraft had lower SVG failure rates and trends toward better long-term clinical outcomes compared with pts. whose SVG were preserved in saline- or blood-based solutions(Harskamp, JAMA Surgery 2014).

  4. A graft preservation solution that maintains functional/structural viability of endothelium improves long-term patency(Harskamp, Ann Surg 2014). Multi-photon imaging of SVG from CABG pts. showed that within minutes of storage in a standard preservation solution (e.g. saline- or blood-based), Ca mobilization and NO generation as a marker for EC functionwere markedly diminished with >90% of EC no longer viable in the vein. In contrast, SVG could be stored for 24 hours without substantial loss in cell viability in the newly formulated heparinized physiologic buffered salt solution GALA (DuraGraft) containing glutathione, ascorbic acid, and L-arginine (Thatte, Ann ThoracSurg 2003) EC= Endothelial cells. Green fluorescence indicates cell viability; red fluorescence indicatescompromised cells. Heparinized lidocaine saline (HLS), autologous heparinizedblood (AHB), tissue culture medium (TCM) , Hank’s balanced salt solution (HBSS), and GALA(DuraGraft). Lack of EC integrity was observed after short-term storage in HLS, AHB, and TCM. EC viability was well preserved only in short-term storage in HBSS . EC remained viable in SV preserved in GALA up to 24 hours.

  5. DURAGRAFT is not just a buffered solution, but also has glutathione, ascorbic acid and L-arginine that help preserve the integrity and function of the endothelium of both venous and arterial grafts • Standard solutions in clinical use today both saline- and blood-based lead to profound decline in conduit viability. [Cardiovascular Res (Suppl.) 2014] • Even short-time storage in physiologic saline solution (acidic pH of 5.5) significantly impairs endothelial vascular function (Wilbring, EurJ CardiothoracSurg 2011). • Once outside the circulation, blood loses its protective effects. Due to decrease in pCO2 ex vivo, there is a rapid loss of CO2 from the blood leading to increase in pH as high as 8.0. Alkaline pH affects the EC and SMC function due to loss of ionic balance [Thatte, JAMA Surgery (Letter) 2014]. • The three key ingredients added to the GALA solution (DuraGraft) were chosen because of their putative effect on endothelial cell function(Thatte, Ann ThoracSurg 2003) • Glutathioneas a cellular reducing agent has been found to increase L-arginine transport in EC and may lead to the stimulation of eNOS activity, nitric oxide generation, and coronary vasodilatation. • Ascorbic acid is an antioxidant known to scavenge reactive oxygen species and also increases eNOS activity by preserving endothelium-derived nitric oxide bioactivity. • L-arginine is a known substrate of nitric oxide synthase and has been shown to decrease neutrophil-endothelial cell interactions in inflamed vessels .

  6. A Preservation Solution for Vascular Grafts LikeDuraGraftReally Matters