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Biomedical subjects

L R Sauvage

Publications and source records attributed to L R Sauvage.

At least 19 recordsLinked to original sources

Transcranial Doppler intraoperative monitoring during carotid endarterectomy: experience with regional or general anesthesia, with and without shunting.

To determine whether continuous transcranial Doppler (TCD) can significantly alter therapeutic conduct during carotid endarterectomy, a retrospective study of 117 carotid endarterectomies was done. There was no perioperative mortality; one perioperative stroke was recorded in a patient who was symptomatic preoperatively. Continuous TCD of the ipsilateral middle cerebral artery (MCA) was attempted in 99 cases, and successful in 90; nine patients (9.1%) had inadequate temporal windows for MCA access. MCA velocities and emboli were recorded before and during carotid cross-clamping, and on clamp release. There were no significant velocity differences between the patients with regional and general anesthesia, and patients with and without carotid shunts, but there was a statistically significant difference in the total number of emboli (air and particulate transients) noted for the shunted and nonshunted patients after clamp release: 12.7 versus 23.6, respectively (p = 0.05). There was no significant difference when particulate and air microemboli were compared. During surgery TCD identified residual flow of less than 40% in the MCA in 17 patients (18.8%). TCD also identified hyperperfusion in two patients, shunt abnormalities in three patients, and influenced postop treatment in four patients, one of whom was returned to surgery. TCD is an important tool for identifying patients who would benefit from a shunt, preventing hyperperfusion, identifying postop emboli, and detecting technical errors.

Aged

Accelerated endothelialization model for the study of Dacron graft healing.

Accelerated endothelialization was studied by creating a vascular tissue environment around porous Dacron grafts. Three study groups, each containing 10 dogs, were divided equally into 2- and 4-week implant periods, with 8 mm x 6 cm knitted Dacron grafts implanted in the abdominal aorta. Grafts in group 1, the control group, were implanted conventionally. In group 2 each implanted graft was completely wrapped in a resected segment of the autogenous inferior vena cava, with its intima against the wall. In group 3 the adventitial side of the vein was wrapped against the wall. The vein wrap produced accelerated endothelialization as follows: endothelial-like cell coverage scores at 2 and 4 weeks were, respectively, 78% and 98% for group 2 and 80% and 95% for group 3, compared to only 14% and 50% for group 1 (p < 0.05). The neointima, which contained smooth muscle cells, was formed as early as 2 weeks in the vein-wrapped grafts. There were no differences in the speed of healing or in healing patterns according to whether the intimal or the adventitial side of the inferior vena cava was placed against the graft. Histologic findings did not support the hypothesis that accelerated flow surface endothelialization results in direct migration of endothelial cells from the intima of the vein wrap, and there was no clear correlation between the surface endothelial-like cell coverage and microostia. To gain further insight into why accelerated healing occurs in this model, earlier observations accompanied by molecular biology analysis are needed, and vein wrap studies provide a method of comparison for this work.

Animals

Effect of altered blood flow on the caliber and morphology of the internal thoracic artery in the dog.

OBJECTIVE: The purpose of this study was to evaluate in dogs the effect of blood flow alteration on caliber and morphology of in situ internal thoracic arteries. METHODS: Six dogs underwent creation of a unilateral distal arteriovenous fistula between the internal thoracic artery and vein at the sixth rib to create high flow, and in six others the internal thoracic artery was unilaterally skeletonized and dissected. For both groups the contralateral internal thoracic artery served as the control; sides were alternated among cases. Blood flow was measured for shear stress calculation before and after surgical alteration. After 2 months, internal thoracic arteries were harvested with the entire anterior chest plate, which was dynamically inflated and fixed with 10% formalin at a controlled pressure of 120 mm Hg after angiography had been done at the same pressure. The luminal diameters were then measured at eight levels on the angiograms. Arterial tissue samples were taken at three levels and embedded, sectioned, and treated with hematoxylin-eosin and Verhoeff-van Gieson stains. Digital imaging analysis was used for quantitative morphometric studies. RESULTS: All fistulas remained patent. In comparison with control arteries, high-flow internal thoracic arteries dilated and low-flow internal thoracic arteries narrowed, which was associated with significant change in shear stress for both groups. There were no substantial structural changes in the walls of either group. CONCLUSION: In the dog, the luminal diameter of the internal thoracic artery responds to altered blood flow without intimal thickening or other undesirable wall changes.

Animals

Implant site influence on arterial prosthesis healing: a comparative study with a triple implantation model in the same dog.

PURPOSE: The purpose of this study was to develop a cost-effective canine graft healing model that gives information on various implant sites and controls for variable factors between graft locations and between animals and to compare the influence of implant site (retropleural, retroperitoneal, and subcutaneous areas) on arterial graft healing in the same subject under such controlled study conditions. METHODS: Five mongrel dogs were studied for 8 weeks, and one was studied for 3 years. Each received three porous Dacron grafts during the same surgery: a carotid-femoral bypass (C-FB) and interposition grafts in the descending thoracic aorta and abdominal aorta. To produce comparable shear stress calibers of the C-FB and abdominal aorta grafts were 2 mm less than those of the descending thoracic aorta, and a distal arterio-venous fistula was created to further increase the C-FB flow. For comparable blood aggregation status platelet aggregation was preevaluated and adjusted with antiplatelet agents. Graft flow surfaces were assessed for thrombus-free surface and endothelial-like cell coverage scores. Tissue samples were studied with hematoxylin-eosin, factor VIII/ von Willebrand factor, smooth muscle alpha-actin staining, and scanning electron microscopy and transmission electron microscopy. RESULTS: All grafts were patent. Shear stress for the three grafts and platelet aggregation among the study subjects were comparable. Healing of descending thoracic aorta and abdominal aorta grafts was similar, but C-FB healing was slow, incomplete, and uneven, with a high incidence of seroma. Eight-week and 3-year results were comparable. CONCLUSIONS: This model gives broad healing information about the areas where grafts are often implanted in humans. Eight weeks appears to be a sufficient period to reflect basic and general healing characteristics. Grafts heal better in the retropleural and retroperitoneal areas than in the subcutaneous tissues.

Animals

Endothelium on the flow surface of human aortic Dacron vascular grafts.

PURPOSE: We have previously observed endothelium on two human vascular prostheses explanted under optimal conditions for flow surface preservation. In this study we sought to further verify the hypothesis that endothelialization can occur on clinical grafts and that it can be detected in specimens that have been promptly removed and properly preserved in a timely manner. METHODS: We studied 29 aortic grafts. Of these, 11 Dacron bypass grafts were in a condition suitable for analysis with light microscopy and immunocytochemistry staining, and scanning and transmission electron microscopy. RESULTS: Three grafts had endothelium beyond the pannus, identified by factor VIII/ vWF, Ulex europaeus agglutinin, and collagen IV positivity. Specimen A, a knitted 6-year implant, was preserved by embalming 3 hours after the patient's death and had a firmly attached outer capsule with fibroblasts, collagen, giant cells, and microvessels in the interstices. Specimen B, a woven 18-year implant, was retrieved at reoperation and immediately fixed in 10% formalin; it had no outer capsule and no tissue ingrowth. Specimen C, a woven 7-year implant, was removed and fixed 5 hours after the patient's death; it had a firmly attached outer capsule but no tissue ingrowth beyond the outer portion of the wall. CONCLUSIONS: The rapidity with which the specimens were fixed probably enabled identification of endothelium. These findings suggest that endothelialization of synthetic arterial grafts may occur more frequently in human beings than previously recognized.

Aged

Histologic observation of continuity of transmural microvessels between the perigraft vessels and flow surface microostia in a porous vascular prosthesis.

To ascertain the histologic relationship between flow surface microostia and perigraft vessels in the healing of a porous vascular prosthesis, a series of careful histologic examinations were carried out on a preclotted, knitted Dacron graft, 8 mm in diameter and 7 cm long, after implantation in the canine infrarenal abdominal aorta for 3 months. Four adjacent longitudinal tissue blocks were taken from the middle for evaluation by means of light microscopy, scanning electron microscopy, transmission electron microscopy, and immunocytochemical staining, and the remainder of the specimen was stained with silver nitrate to allow visualization of microostia and cell borders on the flow surface. Following identification of two microostia adjacent to the area where samples had been taken for general healing evaluation, a 3 x 8 mm full-thickness block containing the microostia was embedded in glycol methacrylate and stained with hematoxylin and eosin. Of 240 serial sections cut from this block, 80 were prepared and examined. Silver staining revealed 42 microostia on the flow surface. Light, scanning, and transmission electron microscopy with endothelial factor VIII/von Willebrand factor stain confirmed a single layer of endothelial cells on the flow surface, and beneath was a well-organized neointima containing fusiform cells confirmed as smooth muscle by alpha-actin stain. Light microscopy of the serial sections revealed transmural microvessels, lined with endothelium, extending continuously between the flow surface ostia and the perigraft vessels in this porous vascular prosthesis.

Animals

Differential effect of the retropleural and retroperitoneal environments on healing of the inner wall of porous fabric prostheses in the thoracic and abdominal aorta of the same dog.

Healing of the inner wall of the same preclotted knitted Dacron arterial prostheses was compared in the descending thoracic aorta (DTA) and the abdominal aorta (AA) of the same dog. Each of 16 dogs received this dual implantation with study periods of 4 weeks for five dogs, 8 weeks for five dogs, and 16 weeks for six dogs. Healing was studied with light microscopy, scanning electron microscopy, transmission electron microscopy, and immunocytochemistry identification. The outer capsule was firmly adherent to the Dacron framework of all grafts implanted in the DTA; advanced healing of the inner wall of all thoracic grafts was present by 4 weeks, nearly complete healing by 8 weeks, and complete healing by 16 weeks. In contrast, the outer capsule was either not attached or only loosely adherent to the Dacron framework in eight AA grafts (50%), and in these implants no healing of the inner wall occurred beyond the limited perianastomotic pannus zone. In the other eight implants in which the outer capsule was firmly adherent to the Dacron framework, healing was roughly comparable to that in the grafts implanted in the DTA. This study demonstrated that (1) DTA grafts heal faster and more completely than AA grafts, (2) healing and endothelialization are related to the tightness of the outer capsule, (3) there is a high incidence of loose tissue attachment in the AA, and (4) healing of aortic grafts is site specific.

Animals

Comparison of the effect of monopolar and bipolar cauterization on skeletonized, dissected internal thoracic arteries.

The internal thoracic artery is preferable to the saphenous vein for use as a conduit for coronary artery bypass. More extensive use is possible if this artery is mobilized in a skeletonized form to provide greater length. Internal thoracic arteries are usually mobilized with cauterization. This study compared the effectiveness and effects on neighboring areas of division of the branches of the canine internal thoracic artery with bipolar cauterization and monopolar cauterization. Branch closure was significantly more secure in the bipolar cauterization group, with bleeding in 25 (9%) of 279 branches of 15 internal thoracic arteries treated with monopolar cauterization, in contrast to bleeding in 4 (1.3%) of 306 branches in the 15 internal thoracic arteries treated with bipolar cauterization, which were paired with the group treated with monopolar cauterization. The group of internal thoracic arteries treated with monopolar cauterization had a significantly higher prevalence of leakage when luminal pressure was increased from 120 to 160 mm Hg. Scanning electron microscopy demonstrated partial loss of endothelial cells on the flow surface of internal thoracic arteries treated with bipolar cauterization, compared with almost complete loss of endothelial cells around the orificial areas after monopolar cauterization. Secondary bipolar cauterization treatment caused only slightly more damage than primary treatment, but secondary monopolar cauterization was much more severe and extensive than primary treatment. These data suggest that bipolar cauterization is preferable to monopolar cauterization for skeletonized dissection of the internal thoracic artery.

Animals

Definitive proof of endothelialization of a Dacron arterial prosthesis in a human being.

A 10 mm woven Dacron axillofemoral bypass graft was removed from a 65-year-old patient during redo surgery after an implant period of 26 months, because of a large seroma that surrounded the entire length of the graft. Tissue blocks were taken from representative areas along the entire length of the graft surface and evaluated by light microscopy with hematoxylin and eosin and Masson trichrome staining, scanning electron microscopy, transmission electron microscopy, and immunocytochemical staining. Paraffin-embedded sections were stained with smooth muscle cell alpha-actin, which demonstrated smooth muscle cells in the pseudointima, and Ham 56 stain to identify macrophages. Endothelial factor VIII/von Willebrand factor and Ulex europaeus agglutinin identified human endothelial cells on the flow surface, in areas far removed from the anastomoses to the native vessels. This is the first definitive proof in a human of endothelialization of a synthetic arterial graft beyond the pannus ingrowth zone.

Aged

Effect of differential shear stress on platelet aggregation, surface thrombosis, and endothelialization of bilateral carotid-femoral grafts in the dog.

PURPOSE: The purpose of this study was to determine the effects of increased shear stress on the aggregability of platelets as they traverse a long, small-caliber (6 mm) Dacron graft in the dog and on the surface thrombosis and endothelialization of such a graft. METHODS: Each of nine dogs received bilateral carotid-femoral artery grafts, approximately 75 cm long, for 3 months; one graft of each pair had a distal femoral arteriovenous fistula to produce a higher shear rate than the contralateral graft. Platelet aggregation scores were determined on blood withdrawn from the external jugular vein and from the proximal and distal ends of the grafts in each animal. Graft flow rates, which were used in the computation of shear stress, and luminal pressure gradients through grafts were measured during surgery and specimen retrieval. Specimens were studied with light microscopy after hematoxylin and eosin and immunocytochemical staining and by scanning electron and transmission electron microscopy to evaluate the nature, composition, and thickness of the flow surface lining, as well as the transmural healing. RESULTS: Two high-shear stress and two low-shear stress grafts occluded unilaterally; five dogs had bilaterally patent grafts, allowing comparative analyses. All subjects had low platelet aggregability with aspirin. Platelet aggregation scores taken from proximal and distal ends of the grafts were not significantly different. The high-shear stress grafts had significantly more endothelial-like cell coverage (p < 0.0371) than the low-shear stress grafts, less flow-surface thrombus (p < 0.0056), and a thinner surface lining (p < 0.0029), on both the neointima and pseudointima. CONCLUSIONS: In subjects with low platelet aggregation scores, long Dacron grafts do not elevate platelet aggregability of blood flowing through them. High-shear stress grafts have less flow surface thrombus, more endothelialization, and a thinner surface lining than do low-shear stress grafts.

Animals

Mitosis and cytokinesis in subconfluent endothelial cells exposed to increasing levels of shear stress.

An in vitro flow apparatus in combination with cultured endothelium was used to determine the effects of fluid-generated shear stress on cells undergoing mitosis and cytokinesis. Cell responses were recorded by time-lapse video microscopy under phase contrast or Hoffman modulation contrast optics. Completion of cell division in mitotic cells was dependent upon both the initial presence of intercellular attachments and the magnitude of fluid wall shear stress. In nonisolated populations, 95.3%, 69.5%, and 57.1% of the cells completed cell division as opposed to 66.6%, 20.4%, and 11.9% in the isolated cell groups at 2.8, 14.1, and 33 dynes/cm2, respectively. Prestressing cells for 14 h prior to monitoring failed to increase retention of isolated mitotic cells. The presence of neighboring cells facilitated replication by providing an anchoring attachment or a luminal surface for completion of division. Cell detachment most commonly occurred at the onset of cytokinesis when substrate contact areas were minimal and focal contacts were absent. A comparison between no flow controls and shear stress specimens indicated no significant differences in transit times for mitosis and cytokinesis. Thus, subconfluent endothelial cells may be more susceptible to detachment during cell division due to increases in shear stress, the absence of intercellular attachments, and reduced cell-substrate contacts.

Animals

Proof of fallout endothelialization of impervious Dacron grafts in the aorta and inferior vena cava of the dog.

PURPOSE: The purpose of this study was to prove directly whether cells from the blood stream contribute to endothelialization of isolated, impervious Dacron vascular grafts in the dog. METHODS: We designed an 18 cm, three-component graft with two parallel central Dacron limbs; one was made impervious with silicone rubber, and the other was preclotted. This model was implanted in the canine descending thoracic aorta with 30 microns polytetrafluoroethylene grafts anastomosed at each end. An 8 cm, three-component graft completely coated with silicone rubber was implanted in the canine abdominal aorta and inferior vena cava. Implant periods ranged from 4 to 12 weeks. Flow surfaces were studied by use of stereomicroscopy after being stained with silver nitrate, and by use of scanning and transmission electron microscopy, the inner wall and flow surface were studied by light microscopy after hematoxylin-eosin and immunocytochemical staining (the latter for endothelial and smooth muscle cells), and the full wall was studied by light microscopy after hematoxylin-eosin staining. RESULTS: Effective prevention of pannus and transmural ingrowth into the impervious central test grafts was achieved, and scattered islands of endothelial cells were conclusively demonstrated on flow surfaces in each of the three implant sites 4 weeks after implantation. In the descending thoracic aorta, where these grafts were also implanted for 8 and 12 weeks, alpha-actin-positive cells and microvessels were found beneath some of the endothelial islands. CONCLUSION: Fallout endothelialization of Dacron vascular grafts occurs in both the arterial and venous systems of the dog.

Animals

Femoropopliteal bypass with externally supported knitted Dacron grafts: a follow-up of 200 grafts for one to twelve years.

PURPOSE: This article reports our experience with externally supported, preclotted knitted Dacron grafts in femoropopliteal bypass. METHODS: This is a retrospective analysis of a consecutive series of 154 patients who received 200 grafts (175 above knee and 25 below knee). Follow-up extended to 12 years (mean 59 1/2 months). RESULTS: Primary patency rates for the entire series were 75%, 70%, and 47% at 3, 5, and 10 years, respectively. Above-knee grafts had 76%, 71%, and 50% rates and 3, 5, and 10 years, respectively. Below-knee grafts had 65% and 57% at 3 and 5 years, respectively. Limb-salvage rates were 87%, 79%, and 73% at 3, 5, and 10 years, respectively, for the 57 limbs operated on because of critical ischemia. The most significant predictor of graft failure was poor runoff as determined by preoperative arteriography. The effect of poor runoff was most pronounced in the first 3 months. CONCLUSION: Externally supported, preclotted knitted Dacron grafts provide encouraging primary patency rates for above-knee femoropopliteal bypass. Poor leg vessel runoff is a major determinant of early graft failure.

Adult

The direct effect of graft compliance mismatch per se on development of host arterial intimal hyperplasia at the anastomotic interface.

To study the direct and sole effect of compliance mismatch on anastomotic intimal hyperplasia of the host arterial wall and to minimize possible confounding factors, dogs with a low thrombotic potential were selected as experimental subjects. Externally supported 6 cm x 5 mm Dacron grafts with a compliance value of approximately 1/300 of the host artery were implanted into the carotid arteries with end-to-end anastomoses on one side and end-to-side anastomoses on the other. The control graft was an autogenous carotid artery segment 4 cm in length transplanted into the femoral artery. Eight cases (24 grafts) were studied for 1 year and three (nine grafts) for 6 months. All were patent throughout the study period except for two noncompliant grafts with end-to-end anastomoses; thrombosis was the documented cause of occlusion. For the patent grafts, follow-up arteriograms showed no progressive narrowing of noncompliant anastomoses. Whether compliant or noncompliant, light microscopy studies showed slight intimal thickening within 1 to 2 mm of the anastomotic line, possibly the result of the normal healing response to stitch and surgical trauma. Quantitatively, 22 measurements representing longitudinal and circumferential thickness of the neointima were taken at each of the 40 patent noncompliant and 22 patent compliant control anastomoses. There was no statistically significant difference in anastomotic neointimal thickness in compliant and noncompliant grafts or for the different implantation periods. These data suggest that graft/host artery compliance mismatch does not cause arterial intimal hyperplasia at the anastomotic interface.

Anastomosis, Surgical

Axillofemoral bypass with externally supported, knitted Dacron grafts: a follow-up through twelve years.

PURPOSE: The purpose of this study was to review our experience with externally supported, knitted Dacron grafts used for axillofemoral bypass. METHODS: Retrospective analysis was performed on records of 79 consecutive axillofemoral bypass graft operations performed on 77 patients from January 1978 to April 1990. RESULTS: The mortality rate within 30 days of operation was 5% (four of 79); 36 patients died in the follow-up period; none died of graft causes. During this 12-year period (mean follow-up 42 months) three patients were unavailable for follow-up. The primary patency rate was 78% at 5 years and 73% at 7 years, with no change thereafter. Neither the graft configuration (i.e., axillounifemoral [n = 50] vs axillobifemoral [n = 29]) nor patency of the superficial femoral artery had an impact on the primary patency rate. Patients who underwent surgery for disabling claudication (n = 30 grafts) had a primary patency rate of 80% at 6 years compared with 65% at 6 years for those who required surgery for limb salvage (n = 49 grafts); the difference was not significant (p = 0.37). Actuarial survival of patients with axillofemoral grafts was 23% at 10 years compared with 72% in a concurrent population of patients with aortofemoral bypass (p < 0.001). CONCLUSION: These findings indicate that axillofemoral bypass grafts may be appropriate for high-risk patients with severe aortoiliac disease who require revascularization for either limb salvage or incapacitating claudication.

Adult

Platelet aggregometry can accurately predict failure of externally supported knitted Dacron femoropopliteal bypass grafts.

PURPOSE: Our purpose was to evaluate whether a method for quantification of platelet aggregability will predict failure of knitted Dacron femoropopliteal bypass grafts. METHODS: A numerically derived platelet aggregation (PA) score, based on the aggregation pattern and platelet count, was determined in the 40 patients available for platelet analysis who underwent 53 femoropopliteal bypass grafts with preclotted, 6 mm, externally supported knitted Dacron grafts from 1981 to 1991 (mean follow-up 50 months). The preoperative score was found to remain stable after surgery, enabling the use of postoperative values when preoperative values were not available. The PA score was available in 19 patients (23 grafts) before surgery and 23 patients (30 grafts) after surgery. The following factors were analyzed for predicting graft failure by the Cox proportional hazards regression model: PA score, age, gender, history of smoking, coronary artery disease, hypertension, hyperlipidemia, cerebrovascular disease, diabetes, claudication versus limb salvage, site of the distal anastomosis, previous ipsilateral bypass, and state of the runoff as determined by preoperative angiography. RESULTS: Of the studied risk factors, the value of the PA score was the most significant predictor of graft closure (p < 0.0001). An increase of 10 units was associated with an increased relative risk of 2.02. Throughout the follow-up period, 15 of 16 grafts remained patent in patients with a PA score of 15 or less, but only 2 grafts out of 17 remained patent in patients with a PA score of 30 or greater. CONCLUSIONS: These data suggest that the PA score is a potential risk factor for failure of femoropopliteal bypass with externally supported knitted Dacron grafts.

Adenosine Diphosphate

Dextran increases survival of subconfluent endothelial cells exposed to shear stress.

In vitro devices in combination with cultured cells have been used to study the relationship between shear stress and endothelial injury. Almost exclusively, these investigations have used confluent monolayers and conventional culture media as perfusates and reported little cell loss over a wide range of shear stress conditions. In this investigation when subconfluent endothelial cells were exposed to 22 and 88 dyn/cm2 for 2, 8, and 24 h in a perfusate of medium and 5% serum, a progressive cell loss was observed. Lower cell densities were a product of decreased cell proliferation as measured by bromodeoxyuridine (BrdU) incorporation and loss of the initial cell population. Video recordings indicated that cells characteristically detached by proximal cell peeling from the substrate and an aneurysmal rupture of the cell membrane. Cell retention was increased by including 250 and 475 microM neutral dextran (70 kDa) in perfusates. Experimental evidence suggests dextran does not directly stimulate proliferation or correct an osmotic imbalance. This investigation has substantiated that fluid-generated shear stress can cause endothelial denudation and that conditions (subconfluency, time, and perfusate supplementation) under which shear stress is applied are as important for cell survival as shear stress magnitude.

Animals