Biomedical subjects
Publications and source records attributed to A D Callow.
Whereas it has been commonly thought that adding polyethylene oxide PEO to a surface would diminish the capacity of the surface to cause deposition of platelets and of fibrinogen, and to activate complement C3, we present data showing exactly the opposite. These unexpected results are obtained with low molecular weight (2000) PEO, and are not found with higher molecular weight (20,000) PEO.
In an attempt to clarify data obtained from animal models of intimal hyperplasia, we used New Zealand white rabbits, a standardized balloon catheter injury model, and a 0.25% cholesterol supplemented diet. The effects of mechanical injury and hypercholesterolemia separately and combined were determined at the carotid and iliac positions at 12 weeks. En-face planimetry of lesioned intima and measurement of transverse intima-to-media thickness were taken as indices of intimal hyperplasia. No animals received antiplatelet agents or postoperative anticoagulation and all vessels remained patent. Neither procedure alone resulted in statistically significant lesion increase. However, combinations of injury and cholesterol resulted in statistically significant and synergistic lesion enhancement. The quantitative data, coupled with distinctive features noted on scanning electron microscopy and transmission electron microscopy, showed separate and synergistic effects of mechanical injury and cholesterol diet on intimal lesions in this model. Additionally, these effects must be considered in evaluation of animal models of intimal hyperplasia and atherosclerosis. Furthermore, this may help dissect mechanisms of failed revascularizations.
Explore the source record for details and available documents.
Polymer surfaces activate complement pathways resulting in platelet and leucocyte deposition as well as possible release of growth factors. A consequence of these interactions may be early graft failure or intimal hyperplasia leading to late graft failure. C5a generation in human plasma by vascular sutures, both alone and in combination with synthetic vascular prostheses was measured by radioimmunoassay to determine the influence of suture materials on C5a activation. Prolene and ePTFE suture material caused significant activation of C5a (p less than 0.01), while Novafil did not. Both Dacron and ePTFE graft material caused significant activation (p less than 0.01) of C5a. The addition of the suture materials to the ePTFE did not increase the C5a levels above the ePTFE material alone. In contrast, the addition of either Prolene or Novafil suture to Dacron material elevated C5a levels significantly over Dacron alone (p less than 0.01). The combination of Dacron material with ePTFE suture did not increase C5a levels over Dacron alone. The pattern of C5a activation by Prolene, ePTFE and Novafil sutures parallels the relative degree of in-vivo platelet accumulation on these suture materials as previously reported by our group. Since these experiments demonstrate that vascular suture material influences human complement activation, it may be that this interaction contributes to either early or late graft failure by enhancing platelet reactivity or neointimal proliferation, respectively.
Endothelial cell (EC) seeding is postulated as a mechanism of improving patency of small calibre vascular grafts. However, the majority of seeded cells are lost within hours following restoration of blood flow. We postulated that incubating EC in-vitro on a graft will improve adherence and resistance to the sheer stresses of pulsatile blood flow. Fibronectin-treated ePTFE (5 cm x 4 mm ID) seeded with Indium-111-labelled autologous canine EC (1.5 x 10(5) cells/cm2) were incubated for four different time periods; 90 min, 24 h, 72 h and 6 days. Incubated grafts were subjected to blood flow of 75 ml/min for 6 h, in a canine ex-vivo arteriovenous shunt circuit. EC retention during perfusion was studied by measuring gamma activity emitted by the grafts. Cell morphology of non-perfused control groups and perfused groups was compared using scanning electron microscopy (SEM). SEM of control grafts showed progressive EC spreading on the ePTFE surface for up to 72 h incubation. Gamma activity was significantly higher at 6 h perfusion in grafts incubated for 72 h (82 +/- 4%) and 24 h (63 +/- 6%) vs. 90 min (34 +/- 13%, p less than 0.05), and between grafts incubated for 72 h vs. 6 days (55 +/- 7%, p less than 0.05). Perfused grafts incubated for 72 h showed unaltered EC morphology on SEM, few cells remained on 90 min incubated grafts. We conclude that incubating EC on fibronectin-treated ePTFE for 72 h in-vitro after seeding improves cell retention during blood flow.
We reviewed our experience with 29 operations for recurrent carotid stenosis in 27 patients who underwent both their primary carotid endarterectomy and their reoperations at our institution. These 27 patients represent 4% of the 667 patients who underwent primary carotid endarterectomies at our institution and who are included in our carotid follow-up registry. Reoperation was prompted by recurrent symptoms in 19/29 (65.5%) cases. Comparison of long-term stroke prevention in those patients who did (84% at 5 years, 78.6% at 10 years) and did not (90.3% at 5 years, 83.6% at 10 years) develop recurrent stenosis requiring reoperation revealed no statistically significant difference (p = 0.48) when measured from the time of primary operation. The perioperative stroke and death rates for reoperation (3.4% and 0%) were acceptable. We conclude that with our acceptably low perioperative stroke morbidity (3.4%), surgery for recurrent carotid stenosis in symptomatic patients or in asymptomatic patients with high-grade (greater than or equal to 75%) stenosis maintains the durable stroke prevention offered by primary carotid endarterectomy.
Continuing controversy over the role of carotid endarterectomy in stroke prevention is based largely on reports in which high perioperative morbidity and mortality rates obviate possible long-term benefit from the procedure. The purpose of this review is to examine optimal results of carotid surgery in order to describe the potential for the procedure in stroke prevention. Optimal surgical results are compared with optimal medical results in the therapy of symptomatic patients and with optimal nonsurgical results in the therapy of asymptomatic patients. Factors common to series with excellent results, such as patient selection and operative technique, are examined, and problems such as recurrent carotid stenosis and coexisting coronary disease, which continue to plague even the best surgical series, are discussed.
To identify patients undergoing carotid endarterectomy who are at high risk for cardiac events and death, we studied the course of 614 patients with known risk factors who were entered into our carotid follow-up registry. Patients were divided into two groups, group I with overt coronary disease (prior myocardial infarction, angina, significant electrocardiographic abnormalities) (N = 324) and group II without overt coronary disease (N = 290). Group II patients were subdivided into groups with (IIA) (N = 206) and without (IIB) (N = 84) coronary risk factors (cigarettes, diabetes, or hyperlipidemias). Thirty-day, 5-, 10-, and 15-year life-table survival for the groups was: I = 98.5%, 68.6%, 44.9%, 36.4%, respectively; II = 100%, 86.4%, 72.3%, 54.3%, respectively; IIA = 100%, 84.8%, 66.9%, 41.5%, respectively; IIB = 100%, 90.5%, 87.9%, 87.9%, respectively. Overt coronary disease was associated with diminished 30-day (p = 0.03) and late (p less than 0.0001) survival. Risk factors in the absence of overt disease were not associated with diminished 30-day survival. Late survival up to 3 years from endarterectomy was similar in groups IIA and IIB, but later survival was diminished in group IIA. Myocardial infarction was the most frequent cause of death in all groups. Patients with overt coronary disease are at high risk for late cardiac events and death. Patients without overt disease are at less risk than those with overt disease, and in the absence of overt disease, those without are at less risk than those with risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)
To define better the short-term risk and long-term benefit of carotid endarterectomy opposite an occluded carotid artery, we reviewed our experience since 1961. Angiographic data are available for 598 of 670 (89.3%) patients in our carotid registry. In 63 (10.5%) patients the internal or common carotid artery on the side opposite the endarterectomy was occluded. All operations were carried out under general anesthesia with selective shunting based on electroencephalographic criteria. Shunting was required in 29 of 63 (46.0%) patients with contralateral occlusion and 72 of 535 (13.5%) control subjects (p less than 0.0001). Perioperative strokes occurred in 3 of 63 (4.8%) patients with contralateral occlusion and 14 of 535 control subjects (2.6%) (p = 0.23). Perioperative death occurred in 0 of 63 patients with contralateral occlusion and 6 of 535 (1.1%) control subjects (p = 0.40). Life-table cumulative stroke-free rates at 1, 5, and 10 years were 95.2%, 91.0%, and 76.2% in the group with contralateral occlusion and 96.0%, 89.4%, and 84.1% in control subjects (p = 0.25). Life-table cumulative survival rates at 1, 5, and 10 years were 93.1%, 80.8%, and 75.4% in the group with contralateral occlusion and 94.8%, 77.0%, and 57.9% in control subjects (p = 0.58). Carotid endarterectomy contralateral to an occluded carotid artery may be carried out with acceptable risk and late stroke-free and survival rates comparable to those seen in other patients who have undergone carotid endarterectomy.
Increasing knowledge that has accumulated during the past decade reveals that the endothelial cell plays a far larger role than that traditionally assigned to it, namely maintenance of the fluid state of the blood. Unraveling the complex interreactions of the endothelial cell with the other cellular and molecular components of the arterial wall, as well as with the blood and its cellular and particulate components, is leading to better understanding of anastomotic hyperplasia and recurrent stenosis after endarterectomy and balloon angioplasty. More recently with the newly acquired techniques of inserting genetic material into the vascular endothelial cell many new therapeutic possibilities may be developed. Important to the technique of seeding vascular grafts, and the possible use of the genetically modified endothelial cell for gene therapy systems, are the needs to identify the origin of the cell originally seeded and ways to increase their number. Retroviral vectors and genetically conferred antibiotic resistance provide these means.
Since approximately 30% to 40% of autogenous vein bypass grafts to the femoropopliteal level may occlude within 5 years of implantation, additional vein will be required for subsequent revisions. We undertook a study to determine whether the preferential use of an above-knee expanded polytetrafluoroethylene bypass graft to save vein is an appropriate option. We reviewed our experience with 114 above-knee expanded polytetrafluoroethylene bypass reconstructions. Life-table analysis of primary and secondary graft patency was carried out by the method of Peto and statistically analyzed for the influence of clinical indication, runoff as determined by both preoperative and intraoperative completion arteriography, smoking, and diabetes. The 5-year primary patency rate of 57% for patients with claudication was comparable to contemporary randomized or retrospective series with below-knee autogenous vein for that indication, and it was superior to the patency rate for limb salvage. The status of the runoff vessels was an important determinant of outcome. The 59 limbs with good arteriographic runoff (2 to 3 vessels) had a markedly higher 5-year patency rate (70%) than the poor arteriographic runoff (0 to 1 vessels) group (30%). Continued cigarette smoking and diabetes mellitus also appeared to affect adversely primary graft patency in our hands. Our data support the use of preferential above-knee expanded polytetrafluoroethylene grafts in patients with good angiographic runoff. This approach does not appear to prejudice the limb against secondary revisionary procedures or the use of a new autogenous graft, if required.
Hydrogels are a class of synthetic material, composed of a polymer-water matrix and have been proposed as tissue substitutes and drug delivery vehicles. Polyethylene oxide (PEO) hydrogels were synthesized and used to produce coated wires and conduits for baboon blood compatibility studies. Blood-material interactions were studied both by Scanning Electron Microscopy (SEM) and 111In labeled platelet deposition. SEM processing modifications were first evaluated in order to reduce shrinkage and surface distortion incurred during sample preparation of these high water content materials. Pretreatment with 1% tannic acid reduced bulk shrinkage associated with critical point drying by 10-20%. This effect is small, nevertheless, it prevented major sample disruption. Coated guidewires were exposed to baboon blood for one hour in the inferior vena cava and conduits were placed for either 30 or 60 minutes in an ex vivo femoral arteriovenous shunt. Reference materials included Gore-tex, polyethylene and silica-free polydimethyl siloxane (PDMS). In the guidewire studies, 111In labeled platelet levels were highest on Gore-tex (6568.97 platelets/1000 microns 2) and large thrombotic deposits were well visualized by SEM. Formulations containing PEO had low levels of platelet deposition and little evidence of platelet activation was noted by SEM. Shunt studies demonstrated that materials of high PEO content and molecular weight had the lowest levels of platelet deposition. After 60 minutes of blood flow, mean platelet deposition on PDMS and Gore-tex was 50 and 1000 fold higher than on a network composed of 65% PEO 20,000 (p less than 0.05). SEM confirmed these findings.
The possibility of using the vascular endothelial cell as a target for gene replacement therapy was explored. Recombinant retroviruses were used to transduce the lacZ gene into endothelial cells harvested from mongrel dogs. Prosthetic vascular grafts seeded with the genetically modified cells were implanted as carotid interposition grafts into the dogs from which the original cells were harvested. Analysis of the graft 5 weeks after implantation revealed genetically modified endothelial cells lining the luminal surface of the graft. This technology could be used in the treatment of atherosclerosis disease and the design of new drug delivery systems.
Abrupt reclosure of atherosclerotic vessels after percutaneous transluminal balloon angioplasty has been blamed on traumatic dissections and elastic recoil of the vessel wall. Thermal energy with compression produces fusion of separated arterial wall layers, and heat appears to alter the elastic recoil of the vessel wall. Radiofrequency (RF) thermal energy has been used to perform vascular anastomoses and thermal angioplasty. A simple in vivo experiment was designed to describe and quantitate vascular tissue weld strength produced by a range of RF thermal energy levels. Canine carotid arteries were compressed between a pair of modified bipolar forceps that applied RF energy, causing occlusive tissue welds between the apposed intimal surfaces. The strength of the welds was evaluated by measuring the perfusion pressure required to reopen the vessel lumen. A dosimetry range of 0 to 205 joules showed a typical dose-response curve for the relationship between energy applied and bond strength, plateauing at approximately 300 mm Hg. Light microscopy showed fusion of the inner surfaces of the vessel with preservation of vessel wall architecture. Additionally inflation of a bipolar RF balloon catheter in the normal canine carotid lumen produced an alteration of vessel profile angiographically and histologically. Results of these preliminary experiments suggest that balloon angioplasty with adjunctive RF thermal energy may have benefits in reducing the factors causing acute failure of conventional percutaneous transluminal balloon angioplasty.
Polyethylene oxide (PEO), because of its low levels of protein and cellular adsorption, may provide a suitable coating for synthetic small caliber vascular prostheses. PEO/polysiloxane networks were synthesized via an acid-catalyzed epoxy/hydroxyl crosslinking reaction and used to produce conduits with a 4-mm internal diameter. Three networks with nominal PEO molecular weights of 2000, 8000, and 20,000 and all 65% PEO by weight were studied. Blood compatibility was assessed by measuring 111In-platelet and 125I-fibrinogen deposition in a baboon ex vivo shunt, over a 1-hr time period and at a flow rate of 50 ml/min. Differences in material performance were noted particularly after the initial 30-min blood contact period. Materials in the mid and high PEO molecular weight range (8000 and 20,000) had significantly lower levels of platelet adsorption than networks of low PEO molecular weight (2000) at 30 min (P less than 0.005) and 60 min (P less than 0.05). The lowest level of platelet deposition was noted on networks of high PEO molecular weight (20,000). During the observation period, platelet accumulation on this surface was less than one platelet per 1000 microns. Platelet deposition on Gore-Tex was two and three orders of magnitude greater than that on the high molecular weight PEO material at 30 and 60 min, respectively (P less than 0.001). Fibrinogen adsorption was also lower on materials of mid and high PEO molecular weights, when compared with low molecular weight networks (P less than 0.05) and Gore-Tex (P less than 0.05). Scanning electron micrographs confirmed these observations. Overall, platelet and fibrinogen depositions are low for PEO networks, particularly for materials of high PEO molecular weight. This latter observation may be related to increased surface molecular mobility and a relative enhancement of PEO content at the blood-material interface.
Prosthetic bypass grafts placed to the distal lower extremity often fail because of an occlusive tissue response in the perianastomotic region. The origin of the cells that comprise this occlusive lesion and the causes of the cellular proliferation are not known. To increase our understanding of this process we cultured cells from hyperplastic lesions obtained from patients at the time of reexploration for lower extremity graft failure, and we studied their identity and growth factor production in tissue culture. These cultures contain cells that express muscle-specific actin isoforms, shown by immunohistochemical staining, consistent with vascular smooth muscle origin. These cultures also released material that stimulated smooth muscle cell growth. A portion of this activity was similar to platelet-derived growth factor, since preincubation with antibody-to-human platelet-derived growth factor partially blocked the mitogenic effect of medium conditioned by human anastomotic hyperplastic cells. These conditioned media also contained material that competed with platelet-derived growth factor for its receptor, as measured in a radioreceptor assay. Northern blot analysis showed that these cells contain messenger RNA that encodes the A chain but not the B chain of platelet-derived growth factor. In addition, these cells contain messenger RNA that encodes a platelet-derived growth factor receptor. We conclude that cultured smooth muscle cells from human anastomotic hyperplastic lesions express genes for platelet-derived growth factor A chain and a platelet-derived growth factor receptor and secrete biologically active molecules similar to platelet-derived growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)
To document the efficacy of our aggressive surgical approach to stroke prevention, we compiled follow-up data on 619 patients undergoing 993 carotid endarterectomies at our institution since 1970. Following carotid endarterectomy, crude annual stroke incidence, including perioperative strokes (2.2%), was 1.9%. In our symptomatic patients crude annual stroke incidence, including perioperative strokes (2.7%), was 2.1%. This is superior to the annual stroke incidence seen in patients on "optimal" medical therapy as defined by the Canadian Cooperative Study (4.6% in men), the AICLA Study (2.9%), the American Multicenter Trial (8%), and the Canadian- American Cooperative Trial (approximately 5%). In our asymptomatic patients, crude annual stroke incidence, including perioperative strokes (1.1%), was 1.4%. This is superior to nonsurgical therapy for asymptomatic patients with hemodynamically significant or more than 75% stenoses as reported by the Mayo Clinic (3.4%) or Chambers and Norris (2.7%). An aggressive surgical approach to carotid bifurcation atherosclerosis is superior to nonsurgical therapy in symptomatic and selected asymptomatic patients if low perioperative mortality/stroke morbidity rates are achieved.
Explore the source record for details and available documents.