In the SYNTAX Trial 1800 patients with 3vessel or left main CAD randomized to CABG or PCI in a 11 ratio rates of MACCE at 12 months were significantly higher in the PCI group 178 vs 124 P 0002 ID: 594468
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Slide1
Does a Preservation Solution for Vascular Grafts Matter?Slide2
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).
CABG has the most solid evidence from recent RCTs supporting its role in revascularization for stable CAD (Ferguson, Jr., Future Cardiol 2014)
PCI impairs
endothelial
function
; it
only treats
‘SUITABLE’ localized proximal ‘culprit’ lesions but has NO PROPHYLACTIC BENEFIT against new disease.Slide3
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).
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).Slide4
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
.
A graft preservation solution that maintains functional/structural
viability of endothelium
improves
long-term
patency
(Harskamp, Ann
Surg
2014).Slide5
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 .Slide6
A
Preservation
Solution for Vascular Grafts Like
DuraGraft Really Matters