Specific Graft Treatment Solution Enhances Vascular Endothelial Function

Abstract

Background: Saline is still the most widely used storage and rinsing solution for vessel grafts during cardiac surgery despite knowing evidence of its negative influence on the human endothelial cell function. Aim of this study was to assess the effect of DuraGraft©, an intraoperative graft treatment solution, on human saphenous vein segments and further elaborate the vasoprotective effect on rat aortic segments in comparison to saline.

Methods: Human Saphenous vein (HSV) graft segments from patients undergoing aortocoronary bypass surgery (n = 15), were randomized to DuraGraft© (n = 15) or saline (n = 15) solution before intraoperative storage. Each segment was divided into two subsegmental parts for evaluation. These segments as well as rat aortic segments stored in DuraGraft© underwent assessment of vascular function in a multichamber isometric myograph system in comparison to Krebs-Henseleit solution (KHS), a physiologic organ buffer solution.

Results: Potassium-Chloride (KCL)-induced contraction depicted a tendency towards increase when treated with DuraGraft© compared to saline preservation of HSV segments (23.02 $\pm$ 14.77 vs 14.44 $\pm$ 9.13 mN, p = 0.0571). Vein segments preserved with DuraGraft© showed a significant improvement of endothelium-dependent vasorelaxation in response to cumulative concentrations of bradykinin compared to saline treated segments (p $<$ 0.05). Rat aortic segments stored in saline showed significantly impaired vasoconstriction (3.59 $\pm$ 4.20, p $<$ 0.0001) and vasorelaxation when compared to KHS and DuraGraft© (p $<$ 0.0001).

Conclusions: DuraGraft© demonstrated a favorable effect on graft relaxation and contraction indicating preservation of vascular endothelial function.

Clinical trial registration number: NCT04614077.

Keywords: coronary artery bypass grafting; endothelium; myograph; preservation solution; vein graft.

Fig. 1.

Effect of preservation solution on contractile responses in HSV. (A) In response to the high $K^{+}$ (KCl) Krebs solution, the HSV segments showed tendency toward increase when stored in DuraGraft© compared to normal saline preservation (23.02 $\pm$ 14.77 vs 14.44 $\pm$ 9.13 mN, p = 0.0571). (B) In response to NE, HSV segments showed no difference between the storage conditions (Saline 85.31 $\pm$ 33.9% and DuraGraft© 72.66 $\pm$ 33.13%; p = 0.167). The NE response is expressed as percentage of KCl contraction. n = 15 patients and n = 23–25 segments/condition.

Fig. 2.

Endothelial dependent and independent vasorelaxation-saphenous vein grafts. Effects of NaCl (black) and DuraGraft® (red) on vascular reactivity in the saphenous vein grafts. (A) Vein rings were precontracted with NE and relaxed with the cumulative dosages of Bradykinin. The Bradykinin response is expressed as percentage of the maximum NE response and baseline tension. (B) Sapneouse vein were precontracted with NE and relaxed with the cumulative dosages of sodium nitroprusside (SNP). The SNP response is expressed as percentage of the maximum NE response and baseline tension. Data are expressed as mean $\pm$ SD, n = 15 patients n = 23 segments/condition.

Fig. 3.

Contractile response and endothelial dependent vasorelaxation-rat aorta. (A) Aorta segments that were kept in DuraGraft© or Krebs-Henseleit solution (KHS) showed comparable response to KCl (contraction; 20.97 $\pm$ 3.37 mN vs 22.87 $\pm$ 2.57 mN) until saline stored segments showed significant impairment in vasoconstriction (3.59 $\pm$ 4.20 mN, p 0.0001). (B) Rat aortic rings were precontracted with PE and relaxed with the cumulative dosage of ACh Physiological treated aorta segments had a significantly impaired endothelial function compared to both DuraGraft© or KHS treated ones (***p 0.0001 KHS vs saline; ^###p 0.0001 DuraGraft© vs saline). Data are mean $\pm$ SD, n = 3 rats and 4 segments/rat.

Fig. 4.

Human Umbilical Vein Endothelial Cells-Viability. Effects of standard medium, NaCl, DuraGraft® and Krebs-Henseleit solution (KHS) on HUVECs viability after (A) 30 minutes and (B) 1 h incubation with the respective conditions. (C) Representative images of the cell morphology under the respective conditions after 1 h. Data are mean $\pm$ SD, n = 7–16 replicates/condition ***p 0.0001 vs saline (NaCl).