Transcript Document

Does a Preservation Solution for
Vascular Grafts Matter?
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; it only treats ‘SUITABLE’ localized proximal
‘culprit’ lesions but has NO PROPHYLACTIC BENEFIT against new disease.
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 that CABG
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).
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 function were 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 Thorac Surg 2003)
EC= Endothelial cells.
Green fluorescence indicates
cell viability; red fluorescence
indicates compromised cells.
Heparinized lidocaine saline
(HLS), autologous heparinized
blood (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.
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, Eur J Cardiothorac Surg 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 Thorac Surg 2003)
• Glutathione as 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 .
A Preservation Solution for Vascular
Grafts Like DuraGraft Really Matters