4.6 Article

Graft Preservation Solution DuraGraft(R) Alleviates Vascular Dysfunction Following In Vitro Ischemia/Reperfusion Injury in Rats

Journal

PHARMACEUTICALS
Volume 14, Issue 10, Pages -

Publisher

MDPI
DOI: 10.3390/ph14101028

Keywords

ischemia/reperfusion; endothelial function; DuraGraft(R); coronary artery bypass grafting

Funding

  1. Land Baden-Wurttemberg, Germany
  2. Medical Faculty of the University of Heidelberg, Germany [NVKP_16-1-20160017]
  3. National Research, Development and Innovation Fund of Hungary [NVKP_16]
  4. Thematic Excellence Programme [2020-4.1.1.-TKP2020]
  5. Ministry for Innovation and Technology in Hungary

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DuraGraft(R) has been shown to improve vascular function of arterial grafts subjected to IRI, protecting endothelial function and enhancing vascular contractile ability.
Vascular ischemia/reperfusion injury (IRI) in patients undergoing coronary artery bypass grafting can result in graft failure and the need for repeat revascularization procedures. DuraGraft(R) has been shown to protect structure and function in saphenous vein grafts against IRI. We compared the effect of DuraGraft(R) to saline solution on arterial grafts submitted to IRI. Rat thoracic aortic rings were harvested and immediately mounted in organ bath chambers (control, n = 7 rats) or underwent cold ischemic preservation either in saline (IR, n = 9 rats) or DuraGraft(R) (IR+Dura, n = 9 rats). Vascular function was measured ex vivo and immunohistochemistry was performed. Impaired maximum vasorelaxation (R-max) to ACh in the IR-group compared to controls was ameliorated by DuraGraft(R), indicating an improvement in endothelial function (R-max to ACh (%): IR + Dura 73 & PLUSMN; 2 vs. IR 48 & PLUSMN; 3, p < 0.05). Additionally, decreased aortic ring sensitivity to ACh (pD(2)-value: -log 50% maximum response) seen after IR in the saline group was increased by DuraGraft(R) (pD(2) to ACh: IR+Dura 7.1 & PLUSMN; 0.1 vs. IR 6.3 & PLUSMN; 0.2, p < 0.05). Impaired maximum contractile response to phenylephrine and high potassium chloride concentrations in the IR group compared to controls was significantly improved by DuraGraft(R). DuraGraft(R) alleviates vascular dysfunction following IRI by reducing nitro-oxidative stress and the expression of ICAM-1, without leukocytes engagement.

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