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Biomedical subjects

R L McCann

Publications and source records attributed to R L McCann.

At least 73 records · Page 4Linked to original sources

Transluminal angioplasty of venous stenoses in polytetrafluoroethylene vascular access grafts.

Since 1984, percutaneous transluminal angioplasty (PTA) utilizing high pressure balloon catheters has been used as an initial approach to restore patency of PTFE (polytetrafluoroethylene, GORE-TEX) hemodialysis vascular access grafts. Seventeen stenotic lesions detected by fistulogram underwent elective PTA. Twelve of these lesions were detected after thrombectomy and five were detected because of increased venous pressures during dialysis. Fourteen attempts at PTA were completely successful in restoring functional patency to the vascular graft. Three attempts were unsuccessful; two of these three grafts were subsequently repaired surgically. Venous stenoses that extended far greater than 6 cm were not considered for PTA. We conclude that PTA is a technique of promise in the non-surgical salvage of failing PTFE grafts. PTA can prolong the useful life of PTFE vascular access grafts and can be performed on an outpatient basis, eliminating the hospitalization that is usually required for surgical revision.

Adult↗

Responsiveness of vein bypass grafts to stimulation with norepinephrine and 5-hydroxytryptamine.

The in vitro reactivity of vein bypass grafts to norepinephrine (NE) and 5-hydroxytryptamine (5-HT) was studied in 20 rabbits undergoing bypass grafting. In these animals the right external jugular vein was grafted into the right carotid artery. The cumulative dose-response to NE and 5-HT of rings of vein grafts 2, 4, and 6 weeks after insertion was compared with that of rings from the normal contralateral jugular vein by means of an organ bath to measure changes in isometric tension. With NE there was no significant difference in the response of vein grafts harvested at 2 weeks and control veins. However, at 4 and 6 weeks there was a progressive decrease in the sensitivity of the grafts to NE. The difference in ED50 values (ED50 defined as concentration of agonist required to elicit 50% of the maximal response) between control veins and vein grafts at 4 weeks was twofold and at 6 weeks it was fivefold. None of the control veins responded to 5-HT stimulation. However, the vein grafts contracted with 5-HT, exhibiting sigmoid dose-response curves. The vein grafts showed intimal hyperplasia, which was maximal after 4 weeks. These results show that vein grafts undergo a progressive decrease in their sensitivity to norepinephrine and develop a marked, sustained increase in sensitivity to 5-HT. This finding is in contrast to previous observations in intimal hyperplastic rabbit aorta, suggesting a fundamental difference in the functional expression of arterial and venous intimal hyperplasia.

Animals↗

Stenoses in dialysis fistulas: treatment with percutaneous angioplasty.

Percutaneous transluminal angioplasty (PTA) was performed on 30 stenotic lesions in 25 dialysis access fistulas. The fistulas were in 23 patients with a mean age of 53 years. Lesions were detected with angiography within a few days after poor flow or increased venous pressure was documented during dialysis. Twenty-two lesions were in patients with polytetrafluoroethylene graft fistulas, five were in patients with bovine carotid fistulas, and three were in patients with endogenous arteriovenous fistulas. There were 28 venous stenoses (20 at the anastomotic site and eight more proximally) and two arterial stenoses. The overall success rate was 80%, with a 6-month patency of 76% and a mean patency after PTA of 9.4 months. Among the venous lesions, the success was 100% for proximal lesions and 71% for anastomotic lesions. There were two technical failures, which required surgery for revision of the fistulas, and four self-limited hematomas. PTA is a safe and effective treatment for stenoses in dialysis fistulas, particularly for lesions remote from the anastomotic sites.

Adult↗

The role of aspirin and dipyridamole on vascular DNA synthesis and intimal hyperplasia following deendothelialization.

Platelets are implicated both in acute thrombotic events and, through platelet-derived growth factor, in the development of intimal hyperplasia. We have investigated, in vivo, the influence of aspirin and dipyridamole on vascular smooth muscle cell proliferation and DNA synthesis following balloon catheter injury. Fifty-eight male, New Zealand white rabbits were divided equally into two groups; the test group was fed aspirin (14 mg/kg/day) and dipyridamole (9 mg/kg/day) from 2 days prior to surgery until sacrifice at 1, 2, 3, 4, 7, 14, or 28 days after injury. All animals were sacrificed 1 h after injection of [3H]thymidine and the smooth muscle cell DNA specific activity and total kinetic activity were determined. Intimal hyperplasia was measured by light microscopy and intimal nuclear proliferation was determined by counting nuclei per millimeter of internal elastic lamina. Nuclear proliferation was maximal at 14 days (25 +/- 1.2) but intimal hyperplasia was still increasing at 28 days. DNA specific activity after 24 hr (test: 4 +/- 2 dpm/micrograms DNA; control: 3.3 +/- 3 dpm/micrograms DNA) was similar to basal levels in uninjured rabbits. DNA synthesis peaked in both groups between the second and third day (test: 177 +/- 27 dpm/micrograms DNA; control: 185 +/- 39 dpm/micrograms DNA) and then declined slowly toward baseline values. There was no significant difference between treated and normal rabbits in either [3H]thymidine incorporation, nuclear proliferation, or development of intimal hyperplasia despite 90% inhibition of platelet aggregation and a significant reduction (78%) in [14C]serotonin release following collagen challenge (6 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Heparin-associated thrombocytopenia and thrombosis: a serious clinical problem and potential solution.

Heparin-associated thrombocytopenia and thrombosis (HATT) is an unusual but serious complication of heparin therapy. Twenty-five patients (13 men and 12 women) had thrombocytopenia and arterial or venous thrombosis 1 to 10 days (mean, 6.3 days) after the start of heparin administration. The vessels in the affected extremity had been entered for catheterization, arteriography, or passage of a balloon counterpulsation device in 19 of the 25 patients. In vitro platelet aggregation with heparin was seen in all patients. Additional studies were performed to see whether other lots or sources of heparin also produced in vitro aggregation. Four separate lots of beef lung heparin, commercial heparin from porcine intestinal mucosa, and two types of low molecular weight heparin were all highly stimulatory in this system. However, Org 10172, a heparinoid, did not induce aggregation in any of 13 patient plasmas tested. Inhibition of platelet aggregation by aspirin was also examined. Aspirin abolished in vitro aggregation in 9 of 16 cases and decreased the degree of aggregation from 85% to 55% (p = 0.02) in the remaining seven cases. We conclude that in patients with HATT platelet aggregation is equally induced by beef lung, porcine intestinal, and some forms of low molecular weight heparin. Org 10172 does not stimulate platelet aggregation in plasma from these patients in vitro. Finally, there may be a role for aspirin in treating patients with HATT.

Aspirin↗

Increased vascular contraction and sensitivity to norepinephrine after endothelial denudation is inhibited by prazosin.

The vasomotor function of rabbit aorta was examined after deendothelialization with a Fogarty balloon catheter and during the subsequent development of intimal hyperplasia. Helical strips of injured lower abdominal aortic tissue showed an increase in norepinephrine-induced contraction when compared with control strips from normal upper abdominal aorta. This increase was 235% +/- 40% of control immediately after injury and 341% +/- 51% at 28 days after injury. Standardized dose-response curves demonstrated that the injured tissue was increasingly sensitive over time to norepinephrine and that this was more marked at physiologic levels of norepinephrine. Contraction was blocked by prazosin hydrochloride but not by yohimbine or propranolol. Furthermore, a single intramuscular dose of prazosin hydrochloride 2 hours before injury significantly (p = 0.001) reduced the maximal contraction and sensitivity. These results imply an increase in vasomotor reactivity after deendothelialization mediated through the alpha 1-adrenergic receptor. These functional changes are related to the pertinent morphologic observations.

Animals↗

Diagnosis of arteriovenous fistula by venous oxygen saturation: case report.

Peripheral arteriovenous fistulas may produce significant deleterious hemodynamic effects yet their diagnosis may not be obvious. A case is described in which the diagnosis of peripheral arteriovenous fistula was suspected from pulmonary artery catheterization data. The fistula was then localized by means of venous catheterization performed at bedside and determination of oxygen content of venous blood above and below the fistula.

Aged↗

Effects of rabbit platelets on vascular smooth muscle cell DNA synthesis.

During platelet aggregation a factor is released which stimulates DNA synthesis in vascular smooth muscle cells. We have examined the capacity of plasma free suspensions of intact rabbit platelets to stimulate DNA synthesis in vascular smooth muscle cells in tissue culture. Platelet-rich plasma was obtained by low-speed centrifugation of citrated blood and passed through sterile columns of sepharose 2B beads. The resultant plasma-free platelet suspension was adjusted to 400,000 platelets/mm3. An aliquot was completely aggregated with thrombin, centrifuged and the supernatant examined for ability to stimulate incorporation of [3H]thyrmidine into DNA by cultured vascular smooth muscle cells. Sonication of an aliquot of platelet suspension released an equivalent amount of this stimulating factor. Another aliquot of platelet suspension of identical volume was added directly to the test smooth muscle cells. Stimulation by intact platelets co-cultured with smooth muscle cells was more than twice as great as that of the thrombin-aggregated supernatant. The latter was not increased by increasing the thrombin concentration nor by increasing the time of exposure. The potency of intact platelets was decreased only slightly by segregating them in Millipore chambers indicating the direct contact was not responsible for its enhancement.

Animals↗

Aspirin and dipyridamole decrease intimal hyperplasia in experimental vein grafts.

Release from platelets of a factor mitogenic for smooth muscle cells is a postulated mechanism for the pathogenesis of vascular intimal hyperplasia. In this study the effect of antiplatelet therapy was evaluated. Aspirin (165 mg twice daily) and dipyridamole (25 mg twice daily) were administered to six rhesus monkeys and six were given placebo only. Bilateral vein bypass grafts were placed in the iliac arteries. In addition, to evaluate the relative contribution of adventitial dissection and intimal injury, on one side the carotid artery and femoral vein were stripped of adventitia and on the other side the intima of these vessels were injured by the single passage of an inflated balloon tipped catheter. Animals were killed after 16 weeks. In grafts relative luminal area was determined by a photographic gravimetric method at three standard locations. Femoral veins and carotid arteries were classified as histologically normal or as exhibiting hyperplasia. All vessels with adventitial stripping were normal. All vessels with intimal injury in the placebo group except one exhibited intimal hyperplasia compared to the drug treated group in which over half were normal. Relative intimal area was significantly less in grafts from drug treated animals at all three locations and luminal area greater in two. These data suggest that vascular intimal hyperplasia can be reduced by treatment with antiplatelet agents.

Animals↗

Histological and biochemical studies of vascular autografts.

We have studied nine saphenous vein bypass grafts removed from patients at the time of a second operation. Two grafts had recanalized thrombus, four had severe intimal hyperplasia and three had atherosclerotic-like lesions. In cases of intimal hyperplasia biochemical analysis of graft wall lipid content revealed a pattern identical to normal saphenous vein. We have also compared the histology and lipid content of experimental vein and artery grafts in rhesus monkeys maintained on normal and atherogenic diets for fifteen months. Surgically unmanipulated arterial tissue in atherogenic diet animals developed uncomplicated lipid-containing intimal lesions. Grafts in these same animals developed more severe and more complicated lesions with an even higher lipid content. In this hyperlipidemic animal model the addition of hypertension produced no additional alterations in graft histology or lipid content.

Animals↗

Intimal thickening and hyperlipidemia in experimental primate vascular autografts.

Intimal thickening is a significant cause of late failure of aorto-coronary vein grafts. The microscopic appearance of this thickening has some similarities to the microscopic appearance of arterial atherosclerosis, and it has been suggested that hyperlipidemia may play a role in its pathogenesis. This study examines the morphology and lipid composition of autologous vein and artery grafts in normal and hyperlipidemic rhesus monkeys. Grafts were examined six months after insertion by light and electron microscopy and tissue lipids were determined quantitatively. Intimal thickening occurred in all grafts. Specific morphological and lipid compositional features of the grafts were influenced by the type of tissue used for grafting and the presence or absence of hyperlipidemia. However, the degree of intimal thickening per se could not be related to either of these two factors. It is concluded that surgical transplantation in this model provides the most powerful stimulus for intimal thickening and any additional effect on this process by hyperlipidemia is small.

Animals↗