Wall strength and stiffness of aneurysmal and nonaneurysmal abdominal aorta.
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Aorta, Abdominal↗
Biomedical subjects
M W Webster
Publications and source records attributed to M W Webster.
Percutaneous rotational coronary atherectomy: initial Green Lane and Mercy hospitals' experience.
AIMS: Rotational atherectomy is a new interventional technique and can be used as an alternative percutaneous treatment for selected coronary atherosclerotic lesions. We report the initial Green Lane/Mercy hospitals experience with rotational atherectomy and review the published international experience with the device. METHODS: Patient case notes and prospectively recorded New Zealand national angioplasty data forms were reviewed for basic demographic data and angina symptoms, in-hospital complications and length of the hospital stay. Catheter laboratory worksheets were reviewed to obtain the duration of ablation, burr diameter and adjunctive PTCA balloon diameter. RESULTS: The main indications for rotational atherectomy were heavy lesion calcification, ostial location, or failure of an angioplasty balloon to cross or to dilate the lesion. Procedural success was achieved in 28 of 30 patients (93%). One patient suffered a Q wave myocardial infarction and in another the lesion could not be crossed with the guide wire. Two patients required repeat balloon angioplasty for early reocclusion without other sequelae and one patient had directional atherectomy 2 weeks later for ongoing sumptoms. CONCLUSION: Rotational atherectomy is a useful adjunct to the percutaneous devices available to treat coronary disease.
Adult↗
Does antithrombotic therapy influence residual thrombus after thrombolysis of platelet-rich thrombus? Effects of recombinant hirudin, heparin, or aspirin.
BACKGROUND: Thrombolysis to normal flow in patients with acute myocardial infarction preserves left ventricular function and decreases mortality. Failure of early reperfusion, reocclusion, or residual thrombus may be due to concurrent activation of the platelet-coagulation system. Thus, we hypothesized that the best concomitant antithrombotic therapy (recombinant [r]-hirudin, heparin, or aspirin) will maximally accelerate thrombolysis by r-tissue-type plasminogen activator (rTPA) and reduce residual thrombus. METHODS AND RESULTS: Occlusive thrombi were formed in the carotid arteries of 29 pigs (by balloon dilatation followed by endarterectomy at the site of injury-induced vasospasm) and matured for 30 minutes before rTPA was started, with or without antithrombotic therapy. Thrombolysis was assessed with the use of angiography and measurement of residual thrombus. Pigs were allocated to one of five treatments: placebo, rTPA, rTPA plus r-hirudin, rTPA plus heparin, or rTPA plus intravenous aspirin. No placebo-treated pig reperfused. Two of six animals treated with rTPA alone reperfused compared with seven of seven animals treated with rTPA plus r-hirudin (reperfusion time, 33 +/- 10 minutes), six of seven animals treated with rTPA plus heparin (reperfusion time, 110 +/- 31 minutes), and two of six animals with rTPA plus aspirin. The activated partial thromboplastin time was prolonged in only the rTPA plus r-hirudin group (25 +/- 0.1 times baseline) and the rTPA plus heparin group (5.3 +/- 0.2 times baseline). Residual 111In-platelet and 125I-fibrin(ogen) depositions were lower in the heparin-treated group and lowest in the r-hirudin-treated group (heparin versus hirudin, respectively; incidence of residual macroscopic thrombus was six of six animals versus two of seven [P = .01]; 125I-fibrin(ogen), 170 +/- 76 versus 48 +/- 6 x 10(6) molecules/cm2 [P = .02]; 111In-platelets, 47 +/- 15 versus 13 +/- 2 x 10(6)/cm2, P = .10). No pigs developed spontaneous bleeding. CONCLUSIONS: Thrombin inhibition with heparin or r-hirudin significantly accelerated thrombolysis of occlusive platelet-rich thrombosis, but only the best antithrombotic therapy (r-hirudin) eliminated or nearly eliminated residual thrombus.
Animals↗
Enhanced manipulation of directional coronary atherectomy and coronary angioplasty guide catheters.
Manipulation of thin-walled coronary guiding catheters, especially directional coronary atherectomy guides, may sometimes be difficult. This is particularly so in patients with tortuous or ectatic aorto-iliac arterial systems. To improve torque transmission and eliminate kinking, the introducer catheter or a smaller caliber diagnostic catheter is advanced to within 1.5 cm of the distal guide tip. Connecting the rotating hemostatic valve to the introducer hub or diagnostic catheter proximally allows distal contrast injections and pressure monitoring via this inner catheter. Other methods of enhancing guide catheter manipulation are also discussed.
Atherectomy, Coronary↗
Does laminated intraluminal thrombus within abdominal aortic aneurysm cause anoxia of the aortic wall?
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Aorta, Abdominal↗
Potential influence of intraluminal thrombus on abdominal aortic aneurysm as assessed by a new non-invasive method.
Intraluminal thrombus may play a role in abdominal aortic aneurysm pathogenesis and rupture. The purpose of this work was to demonstrate the feasibility of a new non-invasive method for the determination of the biomechanical features of the aortic wall and luminal boundary in abdominal aortic aneurysm containing intraluminal thrombus. Automated ultrasonographic measures of infrarenal aortic cross-sectional area (A) were obtained on-line along with non-invasive arterial pressure (p) from eight patients of mean (s.e.m.) age 74(3) years, with abdominal aortic aneurysm (mean dimensions 5.9(0.4) x 5.3(0.5) cm) containing intraluminal thrombus. Luminal boundary and abdominal aortic aneurysm wall were scanned separately. Compliance (C) was computed as C = (Amax - Amin)/[Amax(Pmax - Pmin)], where 'max and 'min' represent maximum and minimum values, respectively. Mean compliance was lower for the abdominal aortic aneurysm wall alone than for the luminal surface enclosed by intraluminal thrombus: 4.0(0.9) x 10(-4)/mmHg versus 9.8(1.7) x 10(-4)/mmHg (P < 0.01). Intraluminal thrombus area was nearly constant over the cardiac cycle, indicating that the thrombus is virtually incompressible. This noninvasive method to assess biomechanical features of abdominal aortic aneurysm has potential to further the understanding of the influences of intraluminal thrombus on aneurysm disease.
Aged↗
Evidence-based assessment of the benefit of revascularisation in coronary disease: beyond the randomised trials.
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Adult↗
A device for the application of cyclic twist and extension on perfused vascular segments.
Cyclic strain is known to influence many aspects of vascular cell biology, including macromolecular biosynthesis, cell proliferation, and cell morphology. The simulation of the cyclic strain associated with the vasculature in situ has been carried out mostly using devices that manipulated flat membranes on which the cells of choice are cultured. The purpose of this work was to create an apparatus wherein cyclic strains consistent with those found in native blood vessels could be applied to intact three-dimensional (tubular) specimens perfused ex vivo. The cyclic strain protocols using our apparatus may be any combination of axial stretch and twist. Concurrently, the perfusion flow and shear stress are controlled as desired. Vessel diameter, intraluminal pressure, volume flow, and regional strain are measured and stored on line. To illustrate the application of the device, we present hemodynamic and kinematic data collected from a human saphenous vein segment perfused under steady-flow conditions while subjected to cyclic stretch and twist.
Blood Vessels↗
Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetic Ulcer Study Group.
BACKGROUND: There has been a broad interest in the use of growth factors to treat patients with chronic nonischemic diabetic ulcers. STUDY DESIGN: One hundred eighteen patients were studied in a randomized, prospective, double-blind, multicenter trial comparing treatment with topically applied recombinant human platelet-derived growth factor (rhPDGF) or placebo (vehicle) and were treated until completely healed or to 20 weeks. All patients had aggressive sharp debridement of their ulcers before randomization and repeat debridement of callus and necrotic tissue as needed. The influence of debridement was evaluated by reviewing the records of the office visits where debridement was performed. RESULTS: Forty-eight percent of patients treated with rhPDGF healed compared with 25 percent of patients who received placebo (p = 0.01). The mean percentage of office visits where debridement was performed was comparable for the two treatment groups: 46.8 percent (rhPDGF) and 48.0 percent (placebo). In general, a lower rate of healing was observed in those centers that performed less frequent debridement. The improved response rate observed with more frequent debridement was independent of the treatment group. However, for any given center, the percentage of patients who healed was greater with rhPDGF than placebo. CONCLUSIONS: Wound debridement is a vital adjunct in the care of patients with chronic diabetic foot ulcers.
Anticoagulants↗
Simultaneous inflation of tandem (sequential) angioplasty balloons: a means of simultaneously treating multiple lesions in one coronary artery.
We report a novel approach to dilating multiple lesions in a coronary artery. Through the same guide and over different wires, a 3.5 mm diameter, 20 mm length, and a 3.0 mm diameter, 90 mm length balloon were simultaneously inflated in a right coronary artery. This approach, which simultaneously treats sequential (tandem) lesions of different diameter and length, allows reduction of both the total duration of ischemia and procedural time and may improve early angiographic outcome.
Angina Pectoris↗
Aortic aneurysm in heart transplant recipients.
PURPOSE: The purpose of this study was to define the clinical features of aortic aneurysms occurring in heart transplant recipients. METHODS: Among the 734 patients who have undergone heart transplantation at our institution over the last 14 years, we have identified 12 patients (1.6% incidence) with aortic aneurysms (9 infrarenal, 3 thoracoabdominal), making this the largest reported series of aortic aneurysms (AA) in heart transplant recipients. RESULTS: For nine of the 12 patients with AA (75%), the indication for transplantation was ischemic cardiomyopathy. This indication accounted for only 42% of the overall transplantation group; our data therefore show that the risk of infrarenal AA disease was higher for patients who underwent transplantation for ischemic cardiomyopathy than for other indications (p = 0.02). In two of the patients with thoracoabdominal AA, chronic dissection was identified as the specific AA cause, whereas all of the other patients in the study had nonspecific "atherosclerotic" AAs. All 12 patients were symptom free at the time of initial discovery of the AAs. Two of the patients with infrarenal AA were diagnosed with AAs before transplantation; for the seven remaining patients with infrarenal AAs, the mean time between transplantation and AA discovery was 5.0 years (range 1.2 to 11.8 years). Serial radiologic studies allowed us to determine the AA expansion rate in seven of the 12 patients. This rate varied from 0 to 2.53 cm/yr (mean 1.20 cm/yr; 1.0 cm/yr for infrarenal AA alone). Five patients with infrarenal AA underwent AA repair as the initial treatment. Three others underwent repair after their AAs significantly expanded under observation. Mean AA diameter at the time of repair was 6.9 cm. All three patients with thoracoabdominal AAs died of acute AA rupture before resection could be done, despite their initial asymptomatic state. AA diameters at time of rupture were 3.5, 6.0, and 11 cm. All of the eight patients with AA treated with surgery are alive and well (median follow-up 18 months). The only complication was acute heart transplant rejection, which occurred 11 days after AA repair in one patient. CONCLUSIONS: Our data suggest that AA occurrence is more likely in patients who undergo heart transplantation for ischemic heart disease than for other indications. Careful serial radiologic surveillance is warranted in any heart transplant patient with an AA, because of the apparent potential for more rapid AA expansion in this patient population than in patients who do not undergo transplantation. We conclude that early repair of infrarenal AA is indicated because excellent operative results and low morbidity rates can be achieved. An aggressive approach to thoracoabdominal AAs in this group may also be appropriate because of the apparent propensity to lethal rupture, sometimes at relatively small AA size.
Aged↗
Compromised cerebral blood flow reactivity is a predictor of stroke in patients with symptomatic carotid artery occlusive disease.
PURPOSE: The purpose of this study was to determine whether the hemodynamic consequences of extracranial carotid disease correlate with the risk of subsequent cerebral infarction. METHODS: In 95 patients with symptoms who had greater than or equal to 70% stenosis (31 patients) or who had occlusion (64 patients) of the ipsilateral carotid artery, cerebral blood flow was measured by the stable xenon/computed tomography technique both at baseline and after vasodilatory challenge with intravenous acetazolamide. Patients were stratified into group 1, 43 patients with no more than a 5% decrease in flow in any vascular territory, and group 2, 52 patients with greater than a 5% decrease in one or more vascular territories after an acetazolamide challenge. RESULTS: In group 2, 15 (28.9%) of 52 patients had a new stroke, but only one (2.3%) of 43 patients in group 1 did (p = 0.0005). Of patients with total carotid occlusion 10 (26%) of 38 in group 2 and none (0%) of 26 in group 1 had a new stroke (p = 0.003). Of patients with greater than or equal to 70% stenosis, five (36%) of 14 in group 2 and only one (6%) of 17 in group 1 had a stroke (p = 0.067). CONCLUSION: The loss of cerebral reactivity in patients with symptoms who had greater than or equal to 70% carotid stenosis or occlusion is an important predictor of impending cerebral infarction.
Acetazolamide↗
Directional coronary atherectomy in the era of stents.
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Angioplasty, Balloon, Coronary↗
Characterization of a dinucleotide repeat in the 92 kDa type IV collagenase gene (CLG4B), localization of CLG4B to chromosome 20 and the role of CLG4B in aortic aneurysmal disease.
Proteolytic imbalance may play a role in the pathogenesis of abdominal aortic aneurysms (AAA). CLG4B, which encodes the 92-kDa form of type IV collagenase, is a candidate gene for AAA. We genotyped a polymorphic dinucleotide repeat in the 5' flanking region of CLG4B in 94 unrelated Caucasian controls and in 127 unrelated Caucasian AAA cases. Eight alleles were detected in 188 control chromosomes with an observed heterozygosity of 0.68. There was no significant difference in allele distribution between cases and controls. We genotyped the dinucleotide repeat in 10 CEPH reference pedigrees and performed pairwise linkage analysis with markers on each of the 22 human autosomes. Lod scores between 10.45 and 20.29 were observed with markers spanning chromosome region 20q11.2-q13.1. Further support for assignment of CLG4B to chromosome 20 was provided by analysis of human-rodent somatic cell hybrids. This work describes a highly polymorphic marker in the CLG4B gene and assigns this gene to chromosome 20.
Aortic Aneurysm↗
Promotion and acceleration of diabetic ulcer healing by arginine-glycine-aspartic acid (RGD) peptide matrix. RGD Study Group.
OBJECTIVE: To determine the effectiveness and safety of arginine-glycine-aspartic acid (RGD) peptide matrix in the treatment of diabetic foot ulcers. RESEARCH DESIGN AND METHODS: This randomized placebo-controlled investigator- and patient-blinded prospective multicenter investigation was conducted at three institutional and three private U.S. clinics providing ambulatory care. Sixty-five diabetic patients with chronic full-thickness neurotrophic foot ulcers were enrolled. Six discontinued the study because of adverse events. RGD peptide matrix (Argidene Gel; formerly Telio-Derm Gel) was applied topically twice weekly for up to 10 weeks in patients who otherwise received standard care. Control group patients received topical saline as a placebo plus standard care. The primary method of assessment was the incidence and rate of ulcer closure. All patients enrolled were included in the data analysis. RESULTS: The percentage of patients whose ulcers healed completely in the RGD peptide matrix group (35%; 14 of 40 patients) was over fourfold greater (P = 0.02) than that in the placebo group (8%; 2 of 25 patients). By the study end point (either day of healing or week 10), 30 of 40 (75%) RGD peptide matrix patients had achieved > 50% ulcer closure compared with 12 of 25 (48%) placebo patients (P = 0.03). RGD peptide matrix also significantly (P = 0.03) increased the rate of ulcer closure over the 10 weeks of the study. CONCLUSIONS: RGD peptide matrix treatment promoted and accelerated the healing of chronic diabetic foot ulcers to a significant degree.
Administration, Cutaneous↗
The effect of arm exercise on regional cerebral blood flow in the subclavian steal syndrome.
Reversed vertebral blood flow distal to a subclavian obstruction is not uncommon and rarely leads to stroke. A small subgroup of these patients have obstruction in other portions of the extracranial or intracranial circulation, however, and cerebrovascular symptoms are induced by arm exercise, which may decrease regional cerebral blood flow--at times to critical levels--indicating a true "steal" syndrome. We evaluated six patients with symptomatic subclavian steal syndrome using stable xenon with computed tomography cerebral blood flow mapping. A decrease in flow from 13% to 90% in one or more regional vascular territories was found after arm exercise. Patients with a true "steal" syndrome may be at higher risk for stroke. Measuring regional cerebral blood flow may be a means of detecting patients who have a critical loss of flow reserves and who will be symptomatically improved by cerebral revascularization.
Acetazolamide↗
Recombinant hirudin in patients with chronic, stable coronary artery disease. Safety, half-life, and effect on coagulation parameters.
BACKGROUND: Because the specific antithrombin hirudin prevents platelet-rich arterial thrombus and accelerates thrombolysis in a variety of animal models, it has promise as antithrombotic therapy. We therefore studied the half-life, effect on anticoagulant parameters, and safety of hirudin in patients with coronary artery disease. METHODS AND RESULTS: Thirty-eight men and 1 woman (age [mean +/- SD], 60.4 +/- 6.9 years) with angiographic coronary disease were allocated in a single-blind ascending dosage study to a 6-hour i.v. infusion of recombinant hirudin (CGP 39,393) or matching placebo. The median terminal half-life for hirudin, measured by ELISA, was 2.7, 2.3, 2.9, 3.1, and 2.0 hours for the 0.02, 0.05, 0.1, 0.2, and 0.3 mg.kg-1 x h-1 groups, respectively. Activated partial thromboplastin times (aPTT) at 3, 4, and 6 hours were averaged into a plateau value. The aPTT plateau-to-baseline ratios were 1.5 +/- 0.1, 2.0 +/- 0.1, 2.3 +/- 0.1, 2.7 +/- 0.1, and 2.9 +/- 0.1, respectively, with hirudin infused at 0.02, 0.05, 0.1, 0.2, and 0.3 mg.kg-1 x h-1. From 62% to 77% of the aPTT plateau value was seen within 30 minutes of starting the infusions and was directly related to dose. The aPTT-to-baseline ratios correlated well with plasma hirudin levels (r = .88), whereas poor correlation and sensitivity were observed between plasma hirudin levels and activated coagulation time (ACT)-to-baseline ratios (r = .44). Plasma levels of hirudin and ACT in seconds correlated overall well (r = .80), but considerable overlap occurred between baseline ACT and ACT at plasma hirudin concentrations < 1000 ng/mL. Prothrombin times were significantly prolonged only at a dosage of > or = 0.05 mg.kg-1 x h-1 and were 11.8 +/- 0.5 (INR = 1.0), 12.3 +/- 0.7 (INR = 1.1), 13.3 +/- 1.2 (INR = 1.4), 14.2 +/- 0.4 (INR = 1.7), and 15.8 +/- 0.9 (INR = 2.3) seconds for each respective hirudin dosage. Thrombin times were beyond range (> 600 seconds) at 6 hours in all except 2 patients who received the lowest dosage. All parameters returned to baseline between 8 and 18 hours after the infusion. Bleeding times were not significantly prolonged. No side effects occurred. No antibodies to hirudin were detected 2 weeks after the infusion. CONCLUSIONS: Recombinant hirudin has a terminal half-life of 2 to 3 hours. The aPTT correlates well with plasma levels of hirudin and allows close titration over a wide range of anticoagulation, while ACT and prothrombin time are relatively insensitive for monitoring hirudin administration. At anticoagulant levels effective in experimental thrombosis, a 6-hour infusion of hirudin is well tolerated and safe in a predominantly male group of patients with stable coronary atherosclerosis.
Aged↗
Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs.
BACKGROUND: Hypercholesterolemia is characterized by a coronary vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. This abnormality may be due to reduced synthesis of endothelium-derived relaxing factor and/or enhanced synthesis and release of an endothelium-derived contracting factor. Endothelin is an endothelium-derived vasoconstrictor and mitogenic peptide that is present in normal plasma, and its circulating concentrations are elevated in disease states that are characterized by abnormal endothelium-dependent relaxation to acetylcholine. The current studies were designed to test the hypotheses that experimental hypercholesterolemia results in elevation of plasma and tissue endothelin immunoreactivity and that the abnormal acetylcholine-evoked coronary vasoconstriction in the hypercholesterolemic animals is associated with further elevation of plasma endothelin. METHODS AND RESULTS: Plasma concentrations and molecular forms of endothelin immunoreactivity were determined following 2% cholesterol diet for 4 months in pigs and during intracoronary acetylcholine administration. Second, we assessed the presence of endothelin in the coronary vascular wall by using immunohistochemistry. Hypercholesterolemia elevated plasma endothelin concentration and enhanced coronary artery tissue endothelin immunoreactivity. The endothelium-dependent vasodilator acetylcholine further increases plasma endothelin in hypercholesterolemia in association with coronary vasoconstriction. The predominant molecular form of endothelin in hypercholesterolemia is the biological active endothelin-1. CONCLUSIONS: This study suggests a role for endothelin as an early participant and a marker for the endothelial dysfunction in hypercholesterolemia as well as a participant in the atherogenic process.
Acetylcholine↗