Wall remodeling after wall shear rate normalization in rat mesenteric arterial collaterals.

Previous studies have demonstrated endothelial and smooth muscle hyperplasia occur during arterial luminal expansion associated with elevation of arterial wall shear rates. The current study investigated whether remodeling induced by elevated wall shear would ultimately result in a vessel with intimal and medial cell densities and other wall characteristics similar to control arteries. A rat mesenteric model was used in which collateral wall shear is restored to normal 4 weeks after arterial occlusion. Twelve weeks after shear elevation, paired in vivo measurements indicated that the maximum collateral inner diameter was increased 27-75%. Morphometric evaluation of collateral cross sections indicated that, relative to control arteries, luminal and medial areas were increased 79 +/- 22 and 56 +/- 15%. Collateral medial cell density was decreased (1.12 +/- 0.044 vs. 1.35 +/- 0.005 nuclei/1,000 micrometer(2) but intimal cell density was similar (2.86 +/- 0.166 vs. 2.49 +/- 0.102 nuclei/100 micrometer luminal perimeter). Medial thickness to radius ratio was also similar between control and collateral arteries. Thus, for the wall characteristics evaluated, there are many similarities between enlarged collaterals and control arteries. Comparison of nuclear numbers in arterial cross sections of the current and previous studies suggest that intimal and medial cellular regression is correlated with a decrease in wall shear force toward normal levels.

Experimental repair of venous valvular insufficiency using a cryopreserved venous valve allograft aided by a distal arteriovenous fistula.

PURPOSE: To evaluate the patency and hemodynamic impact of a cryopreserved allograft venous valve transplanted to the superficial femoral vein (SFV) of a canine insufficiency model aided by a distal arteriovenous fistula (dAVF). METHODS: Eight greyhounds had intravenous hemodynamic parameters measured (venous filling time [VFT], 90% of venous refilling time [VRT90], and simulated ambulatory venous pressure [AVP]) before (T0) and after complete hindlimb venous valvulotomy (T1) to produce venous insufficiency. Simultaneously, a valve-containing vein segment was harvested from the opposite SFV or external jugular vein (n = 1) and cryopreserved. Three weeks later a blood type-matched cryopreserved valve was transplanted to the insufficient SFV aided by a low-flow (n = 4) or high-flow (n = 4) dAVF. The fistula was ligated in 3 to 6 weeks, and venous indexes (T2) were obtained 3 weeks later. Analysis of variances compared the venous indexes at T0, T1, and T2 for statistical significance. Gross and histologic inspection assessed valve integrity. RESULTS: Two valves aided by a low-flow dAVF exhibited thrombosis and scarring. The hemodynamics of the six remaining valves demonstrated normalization of the VRT90, an AVP consistent with insufficiency, and a VFT between normal and total venous insufficiency. The patent valves were normal on gross examination and by histologic examination with signs of normal external healing. CONCLUSIONS: A cryopreserved venous valve allograft transplanted to the SFV of an incompetent hindlimb partially corrects venous hemodynamics. A high-flow arteriovenous fistula most consistently preserves transplant patency.

Wall remodeling during luminal expansion of mesenteric arterial collaterals in the rat.

Wall remodeling associated with rapid luminal enlargement of collateral mesenteric arteries in rats was investigated 1 and 4 weeks after creation of a collateral pathway by ligating three to four sequential arteries. Paired observations were made of inner diameters of collateral and normal arteries in the same animals. Arterial blood flow was measured at the final observation. Sections of arteries were processed for morphological measurements. After 4 weeks, inner arterial diameter was increased more at the beginning (63 +/- 6%) than the end (25 +/- 9%) of the collateral pathway. At 1 and 4 weeks, respectively, cross-sectional areas of collateral relative to normal arteries were increased by 46 +/- 5% and 59 +/- 13% (lumen), 55 +/- 8% and 65 +/- 14% (media), and 89 +/- 18% and 60 +/- 31% (intima). The wall expansion during luminal enlargement resulted in a normal medial thickness:luminal radius relationship. At 1 week postligation, wall shear rate remained elevated and endothelial but not smooth muscle hyperplasia had occurred (intimal nuclei: 40 +/- 1.7 collateral versus 24 +/- 3.0 normal; medial nuclei: 42 +/- 6.8 collateral versus 37 +/- 2.1 normal). At 4 weeks, wall shear rate in collaterals was similar to normal arteries, and smooth muscle hyperplasia had taken place (medial nuclei: 84 +/- 9.4 collateral versus 44 +/- 4.7 normal). The data demonstrate that wall expansion associated with rapid luminal enlargement of these collaterals involves hyperplasia of both endothelial and smooth muscle cells; however, smooth muscle proliferation does not occur until after wall shear rate is reduced. The specific cellular adaptations that occur during collateral development may depend on the level of wall shear and shear-dependent modulation of endothelial growth factors.

Early collateral and microvascular adaptations to intestinal artery occlusion in rat.

The technique to repeatedly observe exactly the same vessels in the rat intestine was used to investigate vascular compensation during the 1st wk after abrupt arterial ligation. A collateral-dependent tissue region was created by ligation of three to four sequential intestinal arteries. At the center of the collateral-dependent region, arterial pressure decreased from 96 +/- 3.7 to 29 +/- 2.5 mmHg, and intestinal blood flow fell approximately 80% during maximal dilation initially postligation. One week later, pressure and blood flow at the center had increased 31 and 250%, respectively. Relative to preligation values, the only compensatory adaptation was an enlargement (31 +/- 11%) of the collateral arteries located between normal tissue and the center; no increase was observed in the diameter or numbers of arterioles or collateral arteries at the center. Wall shear rate was increased 173 +/- 35% initially postligation at the site where luminal enlargement occurred. The selective enlargement of collateral arteries away from the center region is consistent with the hypothesis that collateral enlargement is induced by chronic increases in wall shear rate and can occur independently of tissue ischemia.