Objective: Increased blood flow causes neointimal atrophy, whereas relief of wall tension with an external wrap causes arterial medial atrophy. To study the effects of blood flow and wall tension separately and together, we applied tight or loose wraps on high-flow or normal-flow iliac arteries in baboons.
Method: Baboon external iliac arteries were wrapped with loose-fitting and tight-fitting expanded polytetrafluoroethylene (ePTFE), leaving part unwrapped. A downstream arteriovenous fistula was constructed on one side to increase blood flow approximately twofold. The arteries were perfusion-fixed with 10% formalin after 4 (n = 5) and 28 days (n = 5).
Results: At 4 days, compared with the unwrapped artery, the loosely and tightly wrapped normal-flow artery showed significant medial atrophy (23% and 30%, respectively; P < .05). The tightly wrapped artery showed a loss of cells (27%; P = .02) but no change in cell density. At 28 days, the medial cross-sectional area was decreased by the tight wrap and loose wrap under normal (45% and 28%, respectively; P < .05) and high (43% and 29%, respectively; P < .05) flow. High flow did not alter the effect of wrapping nor did it affect the unwrapped medial area. At 28 days, the normal and high flow tightly wrapped media showed an insignificant loss of cells but had increased cell density (47% and 30%, respectively; P < .05), suggesting preferential loss of extracellular matrix. Decorin was expressed at the late time only in the tightly wrapped normal and high-flow media and was associated with tight packing of the collagen, as detected by picrosirius red staining.
Conclusion: Loose-fitting and tight-fitting ePTFE wraps induced an inflammatory foreign body response that caused medial atrophy with loss of cells and extracellular matrix; the tight wrap was more effective. High blood flow did not prevent or augment medial atrophy.
Clinical relevance: Research in arterial restenosis has focused on the biologic mechanisms and pharmacologic approaches to the prevention of intimal hyperplasia. An alternative therapeutic approach might be to induce atrophy of established intimal hyperplasia. We have previously reported that high blood flow induces neointimal regression in expanded polytetrafluoroethylene grafts in baboons. Here we provide another model of vascular atrophy induced by external wrapping. The similarity between baboons and humans in their vascular systems and individual genetic heterogeneity makes these experiments of great relevance. Up- or down-regulated genes common to both models might be key regulators of vascular atrophy and therefore suitable therapeutic targets for pharmacologic treatment of established lesions.