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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.


Comparison of control (grey) and photochemical tissue passivation (PTP)‐treated (black) vein graft intimal and medial areas at 1‐month. PTP‐treated vein grafts had significantly smaller intimal and medial areas than control vein grafts (data expressed as mean±SD).
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jah31663-fig-0006: Comparison of control (grey) and photochemical tissue passivation (PTP)‐treated (black) vein graft intimal and medial areas at 1‐month. PTP‐treated vein grafts had significantly smaller intimal and medial areas than control vein grafts (data expressed as mean±SD).

Mentions: PTP‐treated venous grafts had a statistically significant decrease in intimal area and intimal thickness compared to the untreated control venous grafts (Figure 5A and 5B). Specifically, intimal area was 3.9 (IQR, 1.2) and 1.3 mm2 (IQR, 0.97; P≤0.001) in untreated and PTP‐treated grafts, respectively, and intimal thickness was 0.74 (IQR, 0.14) and 0.38 mm (IQR, 0.20; P≤0.001) in untreated and PTP‐treated grafts, respectively (Figure 6). Medial area and thickness also exhibited a statistically significantly decrease in PTP‐treated grafts compared to controls. Medial area was 9.2 (IQR, 3.2) and 4.7 mm2 (IQR, 2.0; P≤0.001), and medial thickness was 1.08 (IQR, 0.16) and 0.80 mm (IQR, 0.23; P≤0.01) in untreated and PTP‐treated grafts, respectively (Figure 5A and 5B). In order to control for possible increased intimal thickness attributed to nonpressure fixed vessels, I/M area ratio was performed for each vessel. The I/M of PTP‐treated grafts (0.26 ±mm2 [IQR, 0.25]) remained significantly less than that of controls (0.43 mm2 [IQR, 0.41]; P=0.03). In total, PTP reduced the degree of IH by 66% and medial hypertrophy by 49%.


Photochemical Tissue Passivation Reduces Vein Graft Intimal Hyperplasia in a Swine Model of Arteriovenous Bypass Grafting
Comparison of control (grey) and photochemical tissue passivation (PTP)‐treated (black) vein graft intimal and medial areas at 1‐month. PTP‐treated vein grafts had significantly smaller intimal and medial areas than control vein grafts (data expressed as mean±SD).
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Related In: Results  -  Collection

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jah31663-fig-0006: Comparison of control (grey) and photochemical tissue passivation (PTP)‐treated (black) vein graft intimal and medial areas at 1‐month. PTP‐treated vein grafts had significantly smaller intimal and medial areas than control vein grafts (data expressed as mean±SD).
Mentions: PTP‐treated venous grafts had a statistically significant decrease in intimal area and intimal thickness compared to the untreated control venous grafts (Figure 5A and 5B). Specifically, intimal area was 3.9 (IQR, 1.2) and 1.3 mm2 (IQR, 0.97; P≤0.001) in untreated and PTP‐treated grafts, respectively, and intimal thickness was 0.74 (IQR, 0.14) and 0.38 mm (IQR, 0.20; P≤0.001) in untreated and PTP‐treated grafts, respectively (Figure 6). Medial area and thickness also exhibited a statistically significantly decrease in PTP‐treated grafts compared to controls. Medial area was 9.2 (IQR, 3.2) and 4.7 mm2 (IQR, 2.0; P≤0.001), and medial thickness was 1.08 (IQR, 0.16) and 0.80 mm (IQR, 0.23; P≤0.01) in untreated and PTP‐treated grafts, respectively (Figure 5A and 5B). In order to control for possible increased intimal thickness attributed to nonpressure fixed vessels, I/M area ratio was performed for each vessel. The I/M of PTP‐treated grafts (0.26 ±mm2 [IQR, 0.25]) remained significantly less than that of controls (0.43 mm2 [IQR, 0.41]; P=0.03). In total, PTP reduced the degree of IH by 66% and medial hypertrophy by 49%.

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.