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Photochemical Tissue Passivation Reduces Vein Graft Intimal Hyperplasia in a Swine Model of Arteriovenous Bypass Grafting

View Article: PubMed Central - PubMed

ABSTRACT

Background: Bypass grafting remains the standard of care for coronary artery disease and severe lower extremity ischemia. Efficacy is limited by poor long‐term venous graft patency secondary to intimal hyperplasia (IH) caused by venous injury upon exposure to arterial pressure. We investigate whether photochemical tissue passivation (PTP) treatment of vein grafts modulates smooth muscle cell (SMC) proliferation and migration, and inhibits development of IH.

Methods and results: PTP was performed at increasing fluences up to 120 J/cm2 on porcine veins. Tensiometry performed to assess vessel elasticity/stiffness showed increased stiffness with increasing fluence until plateauing at 90 J/cm2 (median, interquartile range [IQR]). At 90 J/cm2, PTP‐treated vessels had a 10‐fold greater Young's modulus than untreated controls (954 [IQR, 2217] vs 99 kPa [IQR, 63]; P=0.03). Each pig received a PTP‐treated and untreated carotid artery venous interposition graft. At 4‐weeks, intimal/medial areas were assessed. PTP reduced the degree of IH by 66% and medial hypertrophy by 49%. Intimal area was 3.91 (IQR, 1.2) and 1.3 mm2 (IQR, 0.97; P≤0.001) in untreated and PTP‐treated grafts, respectively. Medial area was 9.2 (IQR, 3.2) and 4.7 mm2 (IQR, 2.0; P≤0.001) in untreated and PTP‐treated grafts, respectively. Immunohistochemistry was performed to assess alpha‐smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA). Objectively, there were less SMA‐positive cells within the intima/media of PTP‐treated vessels than controls. There was an increase in PCNA‐positive cells within control vein grafts (18% [IQR, 5.3]) versus PTP‐treated vein grafts (5% [IQR, 0.9]; P=0.02).

Conclusions: By strengthening vein grafts, PTP decreases SMC proliferation and migration, thereby reducing IH.

No MeSH data available.


Proliferating cell nuclear antigen stain demonstrating a greater number of proliferating cells within the intima of control (A) versus photochemical tissue passivation–treated (B) vein grafts. Positive cells (yellow arrows) show a brown nuclear staining. Scale bar=0.1 mm.
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jah31663-fig-0008: Proliferating cell nuclear antigen stain demonstrating a greater number of proliferating cells within the intima of control (A) versus photochemical tissue passivation–treated (B) vein grafts. Positive cells (yellow arrows) show a brown nuclear staining. Scale bar=0.1 mm.

Mentions: PCNA‐positive cells were prominent within the intima and media of control vein grafts, but limited in PTP‐treated vein grafts (Figure 8A and 8B). There was a statistically significant greater PCNA index within the control vein grafts 18% (IQR, 5.3) versus the PTP‐treated vein grafts 5% (IQR, 0.9; P=0.02).


Photochemical Tissue Passivation Reduces Vein Graft Intimal Hyperplasia in a Swine Model of Arteriovenous Bypass Grafting
Proliferating cell nuclear antigen stain demonstrating a greater number of proliferating cells within the intima of control (A) versus photochemical tissue passivation–treated (B) vein grafts. Positive cells (yellow arrows) show a brown nuclear staining. Scale bar=0.1 mm.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

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jah31663-fig-0008: Proliferating cell nuclear antigen stain demonstrating a greater number of proliferating cells within the intima of control (A) versus photochemical tissue passivation–treated (B) vein grafts. Positive cells (yellow arrows) show a brown nuclear staining. Scale bar=0.1 mm.
Mentions: PCNA‐positive cells were prominent within the intima and media of control vein grafts, but limited in PTP‐treated vein grafts (Figure 8A and 8B). There was a statistically significant greater PCNA index within the control vein grafts 18% (IQR, 5.3) versus the PTP‐treated vein grafts 5% (IQR, 0.9; P=0.02).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Bypass grafting remains the standard of care for coronary artery disease and severe lower extremity ischemia. Efficacy is limited by poor long‐term venous graft patency secondary to intimal hyperplasia (IH) caused by venous injury upon exposure to arterial pressure. We investigate whether photochemical tissue passivation (PTP) treatment of vein grafts modulates smooth muscle cell (SMC) proliferation and migration, and inhibits development of IH.

Methods and results: PTP was performed at increasing fluences up to 120 J/cm2 on porcine veins. Tensiometry performed to assess vessel elasticity/stiffness showed increased stiffness with increasing fluence until plateauing at 90 J/cm2 (median, interquartile range [IQR]). At 90 J/cm2, PTP‐treated vessels had a 10‐fold greater Young's modulus than untreated controls (954 [IQR, 2217] vs 99 kPa [IQR, 63]; P=0.03). Each pig received a PTP‐treated and untreated carotid artery venous interposition graft. At 4‐weeks, intimal/medial areas were assessed. PTP reduced the degree of IH by 66% and medial hypertrophy by 49%. Intimal area was 3.91 (IQR, 1.2) and 1.3 mm2 (IQR, 0.97; P≤0.001) in untreated and PTP‐treated grafts, respectively. Medial area was 9.2 (IQR, 3.2) and 4.7 mm2 (IQR, 2.0; P≤0.001) in untreated and PTP‐treated grafts, respectively. Immunohistochemistry was performed to assess alpha‐smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA). Objectively, there were less SMA‐positive cells within the intima/media of PTP‐treated vessels than controls. There was an increase in PCNA‐positive cells within control vein grafts (18% [IQR, 5.3]) versus PTP‐treated vein grafts (5% [IQR, 0.9]; P=0.02).

Conclusions: By strengthening vein grafts, PTP decreases SMC proliferation and migration, thereby reducing IH.

No MeSH data available.