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Purpose: The aim of this project was to evaluate the feasibility of aortoscopy for guidance of endoluminal aortic procedures and to determine whether aortoscopy has advantages over fluoroscopy in a pig model. Methods: To establish feasibility aortoscopic guidance was used for making endoluminal aortic measurements, cannulating small arteries for arteriograpy, and placing intraaortic stents and grafts in 11 pigs. To compare aortoscopy and fluoroscopy measurements were made and stents were placed by a surgeon using only aortoscopic guidance in 10 pigs and by an interventional radiologist using only fluoroscopic guidance in 10 pigs. Postmortem dissections were performed to determine measurement and device placement accuracy. Results: In the feasibility study aortoscopic measurements differed from postmortem measurements by a mean distance (±SD) of 1.2 ± 0.2 mm. Stents and grafts were placed a mean of 2.3 ± 1.9 mm distal to the most inferior renal artery with no stent covering an orifice. All attempts at cannulating spinal arteries greater than 2 mm in diameter were successful. In the comparison of aortoscopic and fluoroscopic guidance, fluoroscopic measurements differed from postmortem measurements by 2.6 ± 2.4 mm ( p = 0.223). Stents placed with aortoscopic guidance were 1.1 ± 1.3 mm distal to the most inferior renal artery, whereas stents placed with fluoroscopic guidance were 3.4 ± 2.5 mm distal to the most inferior renal artery ( p = 0.019). Conclusions: These results demonstrate that aortoscopy is a useful guidance system for endoluminal aortic procedures and may have advantages over fluoroscopy alone. (J Vasc Surg 1996;24:439-48.)

Monoclonal antibodies (mAb) directed against the toxic lipid A portion of lipopolysaccharide (LPS) have been shown to bind lipid A in vitro, but clinical trials of such mAbs have yielded mixed results. In 53 rats instrumented for macrocirculatory and cremaster muscle microcirculatory measurements, we examined whether E5, a murine-derived anti-lipid A mAb, could inhibit LPS-induced circulatory dysfunction when incubated with LPS in vitro or given separately in vivo prior to LPS administration. Compared with Control rats (Group I), rats infused with 10 mg/kg Escherichia coli LPS (Group II) displayed marked decreases in arterial pressure and cardiac output and marked decreases in erythrocyte velocity in second, third, and fourth order skeletal muscle arterioles. Infusion of 2 mg/kg E5 90 min prior to LPS infusion (Group III) did not improve cardiovascular performance. In contrast, incubation of LPS with either 2 mg/kg (Group IV) or 10 mg/kg (Group V) E5 prior to infusion significantly attenuated LPS-induced changes in both macrocirculatory and microcirculatory function. Further investigation of the disparity between the in vitro and in vivo neutralizing capacity of anti-lipid A mAbs may aid interpretation of the variable clinical results achieved with these preparations.

Electron paramagnetic resonance employing a lipid-specific spin label has been used to investigate the molecular effects of endotoxin on the physical state of bilayer lipids in rat erythrocyte membranes. When added at a concentration as low as 40 micrograms/ml to whole blood (plasma plus leukocytes present), decreased membrane lipid motion was found in subsequently washed and spin-labeled intact erythrocytes (P0.02). However, if endotoxin were added to washed, plasma plus leukocyte-free intact erythrocytes, no change in the motion of the spin label was found, suggesting that plasma-soluble substances and/or leukocytes are required to produce the change in the physical state of lipids. The decreased lipid motion found in these studies is discussed with reference to the known decreased deformability of endotoxin-treated red cells and to the pathogenesis of sepsis.

The micropipette aspiration technique was used to quantify membrane deformability of individual red blood cells (RBCs) before and after exposing whole blood and blood free of leukocytes to lipopolysaccharide (LPS). The ability of an anti-lipid A monoclonal antibody (E5) to inhibit the effects of LPS was also investigated. In the LPS/whole blood studies, a significant increase in elasticity modulus was observed following incubation with LPS. An increase in elasticity modulus indicates a decrease in RBC membrane deformability. The effect depended on the incubation time but was not concentration-dependent in the range studied (25, 40, or 170 micrograms/mL). When incubating blood free of leukocytes with LPS, the elasticity moduli of erythrocytes did not change. Results also showed that preincubation of the LPS with E5 prior to incubation with whole blood partially inhibited the effect of LPS, suggesting a possible mechanism of the beneficial actions of monoclonal antibodies in septic shock.

Endothelium-dependent relaxations can be evoked by a variety of stimuli, among them substance P (SP), which is found in sensory nerve fibers supplying the adventitia-media junction of most muscular arteries. This study determined the role of endothelium-derived nitric oxide as a mediator of endothelium-dependent relaxations to SP in isolated rings of the pig carotid artery suspended in organ chambers for isometric tension recording. SP (10(-12)-10(-7) M) caused concentration-dependent relaxations of arteries precontracted with norepinephrine (10(-7) M). The relaxations were characterized by a partially transient relaxation (phase 1) and a sustained relaxation of the artery (phase 2). The inhibitor of nitric oxide formation, N omega-nitro-L-arginine (L-NNA) methyl ester caused a gradual increase in tension, the phase I response at 3 x 10(-10) to 3 x 10(-7) M SP was shifted to the right, but the maximal relaxation was comparable in the presence of L-NNA. However, the sustained relaxation after addition of substance P (phase II) was lost and tension in the presence of L-NNA returned to a level above that induced by L-NNA and norepinephrine (10(-9) M). These results suggest that the endothelium-dependent relaxations to SP, particularly the prolonged relaxation (phase II), are due to de novo synthesis of nitric oxide and hence fully abolished by a specific inhibitor.