Long term follow-up of the endovascular trans-vessel wall technique for parenchymal access in rabbit with full clinical integration.

OBJECTIVE: Endovascular techniques are providing options to surgical/percutaneous cell transplantation methods. Some cells, e.g. insulin producing cells, are not suitable for intra-luminal transplantation and for such cells, other options must be found. We have constructed a "nanocatheter" with a penetrating tip for vessel perforation, thereby creating a working channel for parenchymal access by endovascular technique. To finish the procedure safely, the distal tip is detached to provide a securing plug in the vessel wall defect. MATERIALS AND METHODS: We have performed interventions with full clinical integration in the superior mesenteric artery (SMA), the subclavian artery and the external carotid artery in rabbits. No hemorrhagic- or thromboembolic events occurred during the procedure. Stenosis formation and distal embolisation were analyzed by angiography and macroscopic inspection during autopsy at five, 30 and 80 days. All animals and implanted devices were also evaluated by micro-dissections and histochemical analysis. RESULTS: In this study we show safety data on the trans-vessel wall technique by behavioral, angiographical and histological analysis. No stenosis formation was observed at any of the follow-up time points. No animals or organs have shown any signs of distress due to the intervention. Histological examination showed no signs of hemorrhage, excellent biocompatibility with no inflammation and a very limited fibrous capsule formation around the device, comparable to titanium implants. Further, no histological changes were detected in the endothelia of the vessels subject to intervention. CONCLUSIONS: The trans-vessel wall technique can be applied for e.g. cell transplantations, local substance administration and tissue sampling with low risk for complications during the procedure and low risk for hemorrhage, stenosis development or adverse tissue reactions with an 80 days follow-up time. The benefit should be greatest in organs that are difficult or risky to reach with surgical techniques, such as the pancreas, the CNS and the heart.

The role of endothelin-1 in regulation of rat mesenteric microcirculation.

Immunocytochemistry of endothelin-1 (ET-1) and the ETA receptor, and scanning electron microscopy using cast resin after treatment with ET-1, were carried out in the rat mesenteric microvasculature. Immunoreaction of ET-1 was preferentially seen along the endothelium of the proximal portion of the anterior mesenteric artery, the endothelial cells of which contain abundant Weibel-Palade (WP) bodies. However, the arterioles and small veins distal to the artery showed little immunoreactivity but showed heavy immunoreaction of ETA receptors in the media. By scanning electron microscopy after treatment with ET-1, the mesenteric microvasculature became slightly narrower compared to the control exhibited of localized constricted areas, especially in the region of the small veins. Light microscopy of such areas revealed localized thickening of the medial muscle cells. Because the release of ET-1 from endothelial cells depends in part on extracellular discharge of the WP bodies, the results indicate that ET-1, discharged from the proximal portion of the anterior mesenteric artery, induces vasoconstriction of the arterioles and small veins, mediated by ETA receptors. The localized thickening in areas in the media of the small veins may participate in the maintenance of blood flow through the portal circulation.

Takayasu's arteritis diagnosed at the early systemic phase: diagnosis with noninvasive investigation despite normal findings on angiography.

We describe a case of Takayasu's arteritis discovered at the early systemic phase. Ultrasonography and computed tomography show thickening of the walls of the superior mesentery and common carotid arteries despite normal findings on angiography. Diagnosis was confirmed by arterial biopsy. We emphasize the importance of noninvasive vascular investigation to support the diagnosis of Takayasu's arteritis.

Time course of endothelial dysfunction and neutrophil adherence and infiltration during murine traumatic shock.

Traumatic shock in rats has been shown to induce endothelial dysfunction, and to increase intestinal myeloperoxidase activity (MPO) indicative of neutrophil infiltration. To examine the time course of endothelial dysfunction and neutrophil adherence and infiltration, pentobarbital anesthetized rats, subjected to Noble-Collip drum trauma, were studied prior to and 15, 30, 60, 90, 120, 150, and 180 min following drum trauma. Superior mesenteric artery rings obtained from traumatized rats were tested for responsiveness to acetylcholine (ACh), a receptor-mediated endothelium-dependent vasodilator, and to NaNO2 an endothelium-independent vasodilator. ACh-induced relaxation was not impaired immediately after the induction of trauma (time 0). However, 15-30 min after trauma, responses to ACh were significantly depressed (p < .05) and were further reduced (p < .01) 90-180 min after trauma. No significant changes occurred in response to the direct vasodilator NaNO2 at any of the times studied, indicating no vascular smooth muscle injury. Moreover, the adherence of polymorphonuclear leukocytes (PMNs) to the post-traumatic mesenteric vascular endothelium also showed an increase that peaked 30 min post-trauma. Intestinal MPO activity, indicative of neutrophil infiltration, was characterized by a continuous and sustained increase from 30-180 min. Our findings suggest that endothelial dysfunction resulting in reduced NO release occurs in the early phase of murine traumatic shock, and that this phenomenon is followed by a time-dependent increase in adhesivity of neutrophils to the vascular endothelium leading to a progressive accumulation of PMNs in injured tissues (e.g., intestine).

Endothelin receptors mediating vasoconstriction in rat pressurized small arteries.

The effects of endothelin-1 (ET-1), a nonselective ETA and ETB receptor agonist, and sarafotoxin S6c, a selective ETB agonist, were investigated in the presence and absence of BQ123 and BQ788, ETA- and ETB-selective antagonists, respectively, in rat mesenteric small arteries, using a perfusion pressurized arteriograph in which segments of vessels were cannulated and exposed to constant pressure and flow. ET-1 (10(-13)-10(-7) M) induced vasoconstriction in both intact and endothelium-denuded arteries in a concentration-dependent manner. BQ123 (10(-7) and 10(-6) M) inhibited the effect of ET-1, displacing the concentration-response curve to the right in a concentration-dependent manner. The effect of ET-1 was not significantly affected by BQ788 (10(-7) and 10(-6) M), a selective antagonist of ETB receptors. Sarafotoxin S6c (10(-11)-10(-7) M) also induced a slight concentration-dependent vasoconstriction. The effect of sarafotoxin S6c (10(-8) M) was inhibited by the ETB-selective antagonist BQ788 (10(-7) M), but was not significantly changed by BQ123 (10(-7) M). Vasoconstriction induced by sarafotoxin S6c (10(-8) M) in a single bolus concentration was significantly greater than the contraction induced by the same concentration as part of a cumulative concentration-response curve, indicating desensitization or downregulation of ETB receptors during the latter. Repeated application of single concentrations of sarafotoxin S6c (10(-8) M) caused progressively smaller contraction of arteries. These results show the existence of both ETA and ETB vasoconstrictor receptors located on smooth muscle of small arteries. They also show that ETB receptors induce a smaller constrictor effect, and rapidly undergo desensitization after sustained or repeated activation.

An isolated dissecting aneurysm of the superior mesenteric artery: report of a case.

We report herein the case of a 56-year-old man found to have an isolated dissecting aneurysm of the superior mesenteric artery (SMA) after he presented with a 3-day history of postprandial epigastralgia of sudden onset. An echogram showed marked dilatation of the SMA and a high level of peripheral echoes in a linear fashion within its lumen. A thin-section contrast enhanced computed tomography revealed a thin flap, separating two distinct well-enhanced lumina. Angiography confirmed the presence of a localized dissecting aneurysm of the SMA. The patient was treated conservatively and has since been followed up as an outpatient. Following the presentation of this case, the problems regarding the diagnosis and management of this rare disease are discussed based on a review of the literature.

Ultrastructural studies on the phenotypic modulation of human intimal smooth muscle cells.

The present study was carried out to clarify the mechanism of intimal thickening at the ostia of celiac and superior mesenteric arteries. The cell components involved in the process were analyzed under electron microscope. Autopsy samples from cases without significant atherosclerotic diseases were examined and the percentages of smooth muscle cells in either synthetic or contractile state, macrophages, and foam cells in the intima of mesenteric and celiac arteries were calculated. Smooth muscle cells in the synthetic state were predominant in the proximal region and those in the contractile state were predominant in the distal region. Few macrophages were present in both regions. The intima in the proximal and distal regions of celiac arteries in autopsy samples was further divided into three layers and the percentages of various smooth muscle cell phenotypes in each layer were calculated and compared in patients at different ages. In the proximal region, the phenotype of the smooth muscle cells changed from the synthetic to the contractile state from the deeper to the superficial layers with the advance of age. In the distal region, the contractile state was dominant regardless of the age. These results suggest that the phenotypic modulation of human intimal smooth muscle cells is reversible dedifferentiation-redifferentiation process; this phenomenon plays an important role in the initiation of atherosclerosis.

Three-dimensional characterization of dense bodies in contracted and relaxed mesenteric artery smooth muscle cells.

We have previously shown that dense bodies are not the static planar simple ovoidal structures they appear to be in thin sections. In this report, we present three-dimensional reconstructions from consecutive serial thin sections through shortened and non-shortened large mesenteric artery cells. Profiles of the cell surface, membrane dense bodies, and cytoplasmic dense bodies were reconstructed from consecutive thin sections and the distribution, size, shape, and spatial relationships among these components was examined. Within the cell, membrane dense bodies are numerous and occupy approximately 10% of the cell volume. Membrane dense bodies can attach to the cell surface laterally, obliquely or normally. An individual membrane dense body can be continuous over more than 2 microns of cell depth and can change shape throughout its depth. On cell shortening, many membrane dense bodies assume a crenated shape. Compared to membrane dense bodies, cytoplasmic dense bodies are smaller in all dimensions and occupy about 2% of the cell volume. In shortened cells, cytoplasmic dense bodies appear to cluster into groups. This redistribution of cytoplasmic dense bodies may be related to the reorganization of contractile units when the cell shortens.