Skip to main content

Preservation solutions to improve graft patency: The devil is in the detail

Peer Review reports

We read with great interest the article by Fourquet and colleagues exploring whether autologous heparinized blood (AHB), heparinized saline (HS) and GALA (considered as their reference solution) have a protective effect on vein grafts interposed in the arterial position at 6 weeks post grafting in a syngeneic rat model [1].

The authors report significant intimal hyperplasia irrespective of treatment and further describe an endothelial-remodeling layer associated with an increase in wall thickness in each group at 6 weeks of follow-up. Based on these findings, they conclude that the storage solutions used in their experimental model lead to graft injury and that their reference solution (GALA) did not reduce risk of intimal hyperplasia. The study addresses an important topic and the experimental set up is interesting. However, there are several findings and conclusions that should be taken with caution and need further clarification.

First, we would like to point out that the solution used in the present study and referred to as GALA neither has the same composition as the GALA solution which was developed and used at the Veterans Affairs laboratories in Boston [2] nor is it comparable to the currently commercially available DuraGraft [3, 4]. In fact, it is to be recognized that the solution used by Fourquet and colleagues has an 11.4 mM ascorbic acid concentration which is 23-fold higher than the 0.5 mM ascorbic acid concentration used in the GALA solution or DuraGraft. Second, based on the potassium hydrogenophosphate concentration and the lack of corresponding phosphate acid, there appears to be no buffering capacity for this solution. Given the high concentration of ascorbic acid, this solution will be highly acidic, even in the presence of sodium bicarbonate. Additionally, ascorbic acid used in the concentrations such as described by Fourquet was demonstrated to be highly cytotoxic [5].

Next, with the exception of glucose (which also had a different concentration from GALA and DuraGraft), it is impossible to calculate concentrations of the other components as these were all listed as milliliters added of solutions with no concentrations associated with them.

Importantly, given the increase in ascorbic acid and the significant decreased buffering capacity, it must be assumed that the solution used in the present study had a very low acidic pH (i.e. close to pH 3 or lower). Therefore, this solution is extremely toxic to the endothelium of the implanted vein grafts. The high relevance of pH and proper buffering (to elevate the standard pH of saline from 5.5 up to 7.4) has been extensively described in the literature [6, 7] and has been highlighted in a sub-study of the PREVENT IV trial [8]. In this subanalysis, Harskamp et al. clearly demonstrated that the use of buffered saline was associated with a significantly lower occurrence of vein graft failure (VGF) when compared with NS or AWB [8].

For this reason, the use of a very acidic solution as used, Fourquet’s study would be unlikely to achieve the ultimate goal of endothelial protection thereby preventing the development of vein graft disease (VGD). On the other hand, their results are indeed consistent with those expected when vein grafts are stored in such a low pH acidic solution as used in their study.

Taking these significant differences in composition into account, any reference to the GALA solution or DuraGraft is inappropriate, and in our view, the conclusions made by Fourquet et al. that the GALA solution does not protect the endothelial layer when the vein graft was arterialized in this rat model is misleading and should be revised.

In particular, this is also due to the fact, that their findings are highly contradictory to the preclinical and clinical data available for the hospital compounded GALA solution and the commercially available DuraGraft (which was formulated based on the GALA solution) [2, 4, 9, 10].

In a recent retrospective analysis, Haime et al. showed that treatment of saphenous vein grafts with (the hospital compounded) GALA solution in patients undergoing isolated coronary artery bypass grafting was associated with a 45% lower occurrence of non-fatal MI, a 35% lower risk for revascularization and 19% lower major adverse cardiac events respectively starting at 1000 days post CABG [10]. Moreover, in a randomized multicenter clinical trial using a within-patient randomization design and sequential multidetector computed tomography angiography at 1, 3, and 12 months after CABG, Perrault et al. and colleagues found favorable effects on wall thickness (as a surrogate of VGF/VGD) of DuraGraft treated SVGs at 12 months, particularly in the proximal segments [4]. The study also showed a good safety profile for DuraGraft with very low rates of graft occlusion and occurrence of MI, and no deaths [4]. Finally, although the authors provided some limitations of their study, several important issues remain unaddressed. While they report graft thrombosis rates of 22% in the AHB group, 62.5% in the HS group and 82.5% in the GALA group respectively, these observations were not discussed in the context of one third of animals (3/9) in the GALA group dying during FU, making any meaningful interpretation and statistical analysis impossible. Last but not least, important technical details (i.e. storage time, size and diameter of the venous grafts, etc.) are not provided, but would however be mandatory to know for proper interpretation of the outcomes.

Taken together, while the study of Fourquet and colleagues addresses the important topic of graft patency, the results and drawn conclusions by the authors have to be taken with caution.

Availability of data and materials

Not applicable.


  1. 1.

    Fouquet O, Blossier JD, Dang Van S, Robert P, Barbelivien A, Pinaud F, et al. Do storage solutions protect endothelial function of arterialized vein graft in an experimental rat model? J Cardiothorac Surg. 2020;15(1):34.

    Article  Google Scholar 

  2. 2.

    Thatte HS, Biswas KS, Najjar SF, Birjiniuk V, Crittenden MD, Michel T, et al. Multi-photon microscopic evaluation of saphenous vein endothelium and its preservation with a new solution, GALA. Ann Thorac Surg. 2003;75(4):1145–52.

    Article  Google Scholar 

  3. 3.

    Caliskan E, Sandner S, Misfeld M, Aramendi J, Salzberg SP, Choi YH, et al. A novel endothelial damage inhibitor for the treatment of vascular conduits in coronary artery bypass grafting: protocol and rationale for the European, multicentre, prospective, observational DuraGraft registry. J Cardiothorac Surg. 2019;14(1):174.

    Article  Google Scholar 

  4. 4.

    Perrault LP, Carrier M, Voisine P, Olsen PS, Noiseux N, Jeanmart H, et al. Sequential multidetector computed tomography assessments after venous graft treatment solution in coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2019. [Epub ahead of print].

  5. 5.

    Schmidt RJ, Chung LY, Andrews AM, Turner TD. Toxicity of L-ascorbic acid to L929 fibroblast cultures: relevance to biocompatibility testing of materials for use in wound management. J Biomed Mater Res. 1993;27(4):521–30.

    CAS  Article  Google Scholar 

  6. 6.

    Caliskan E, de Souza DR, Böning A, Liakopoulos OJ, Choi Y-H, Pepper J, et al. Saphenous vein grafts in contemporary coronary artery bypass graft surgery. Nat Rev Cardiol. 2020;17(3):155–69.

    CAS  Article  Google Scholar 

  7. 7.

    de Vries MR, Simons KH, Jukema JW, Braun J, Quax PH. Vein graft failure: from pathophysiology to clinical outcomes. Nat Rev Cardiol. 2016;13(8):451–70.

    Article  Google Scholar 

  8. 8.

    Harskamp RE, Alexander JH, Schulte PJ, Brophy CM, Mack MJ, Peterson ED, et al. Vein graft preservation solutions, patency, and outcomes after coronary artery bypass graft surgery: follow-up from the PREVENT IV randomized clinical trial. JAMA Surg. 2014;149(8):798–805.

    Article  Google Scholar 

  9. 9.

    Pachuk CJ, Rushton-Smith SK, Emmert MY. Intraoperative storage of saphenous vein grafts in coronary artery bypass grafting. Expert Rev Med Devices. 2019;16(11):989–97.

    CAS  Article  Google Scholar 

  10. 10.

    Haime M, McLean RR, Kurgansky KE, Emmert MY, Kosik N, Nelson C, et al. Relationship between intra-operative vein graft treatment with DuraGraft(R) or saline and clinical outcomes after coronary artery bypass grafting. Expert Rev Cardiovasc Ther. 2018;16(12):963–70.

    CAS  Article  Google Scholar 

Download references


Not applicable.


Not applicable.

Author information




EC, CJP and MYE drafted the manuscript. All authors critically revised the manuscript for important intellectual content and approved the final version.

Corresponding author

Correspondence to Maximilian Y. Emmert.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

EC is an investigator in the European VASC registry. EC and MYE are members of the registry scientific advisory board (RAC). MYE is the PI of VASC registry and the chair of the registry scientific advisory board (RAC). MYE and LPP are consultants to Somahlution Inc., Jupiter, FL. CJP is the Chief Scientific Officer at Somahlution Inc., Jupiter, FL.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Caliskan, E., Pachuk, C.J., Perrault, L.P. et al. Preservation solutions to improve graft patency: The devil is in the detail. J Cardiothorac Surg 15, 228 (2020).

Download citation