Showing papers by "David E. Newby published in 2001"

Impaired Coronary Tissue Plasminogen Activator Release Is Associated With Coronary Atherosclerosis and Cigarette Smoking Direct Link Between Endothelial Dysfunction and Atherothrombosis

Abstract: Background—The aim of the study was to establish the influence of proximal coronary artery atheroma and smoking habit on the stimulated release of tissue plasminogen activator (tPA) from the heart. Methods and Results—After diagnostic coronary angiography in 25 patients, the left anterior descending coronary artery (LAD) was instrumented, and the proximal LAD plaque volume was determined by use of intravascular ultrasound (IVUS). Blood flow and fibrinolytic responses to selective LAD infusion of saline, substance P (10 to 40 pmol/min; endothelium-dependent), and sodium nitroprusside (5 to 20 μg/min; endothelium-independent) were measured by intracoronary IVUS and Doppler, combined with arterial and coronary sinus blood sampling. Mean plaque burden was 5.5±0.8 mm3/mm vessel (range 0.6 to 13.7 mm3/mm vessel). LAD blood flow increased with both substance P and sodium nitroprusside (P<0.001), although coronary sinus plasma tPA antigen and activity concentrations increased only during substance P infusion (P<0...

Bradykinin Contributes to the Vasodilator Effects of Chronic Angiotensin-Converting Enzyme Inhibition in Patients With Heart Failure

Abstract: Background Bradykinin, an endogenous vasodilator peptide, is metabolized by ACE. The aims of the present study were to determine the doses of B9340, a bradykinin receptor antagonist, that inhibit vasodilatation to exogenous bradykinin and to assess the contribution of bradykinin to the maintenance of basal vascular tone in patients with heart failure receiving chronic ACE inhibitor therapy. Methods and Results Forearm blood flow was measured using bilateral venous occlusion plethysmography. On three occasions in a double-blind randomized manner, 8 healthy volunteers received intrabrachial infusions of placebo or B9340 (at 4.5 and 13.5 nmol/min). On each occasion, placebo or B9340 was coinfused with bradykinin (30 to 3000 pmol/min) and substance P (4 to 16 pmol/min). B9340 caused no change in basal FBF but produced dose-dependent inhibition of the vasodilatation to bradykinin (P<0.001) but not substance P. The effects of bradykinin antagonism were studied in 17 patients with NYHA grade II through IV heart ...

Association between calcific aortic stenosis and hypercholesterolemia: is there a need for a randomized controlled trial of cholesterol-lowering therapy?

Abstract: Background: Calcific aortic stenosis may have common etiological factors with atherosclerosis. Hypothesis: In this retrospective, case-control study, we aimed to determine whether there is an association between hypercholesterolemia and calcific aortic valve stenosis. Methods: Consecutive patients undergoing single aortic or mitral valve replacement in a regional cardiothoracic surgical center were reviewed and preoperative patient characteristics were recorded: demographics, comorbidity (including coronary artery disease and associated risk factors), serum total cholesterol, lipid-lowering therapy, and serum creatinine. Results: Serum total cholesterol concentrations were significantly higher in patients with calcific aortic stenosis than in controls (6.2 ± 1.1 vs. 5.3 ± 1.1 mmol/l;p< 0.001). The significant difference in serum cholesterol concentrations remained following correction for gender and body mass index (p = 0.02) and when patients with coronary artery disease were excluded (6.3 ± 1.1 vs. 5.3 ± 1.4 mmol/l; p < 0.001). Subgroup analysis demonstrated that the association between elevated serum cholesterol concentrations and calcific aortic stenosis was particularly strong in patients with tricuspid aortic valves (6.4 ± 1.2 vs. 5.3 ± 1.1 mmol/l; p < 0.001) compared with those with bicuspid valves (5.9 ± 1.1 vs. 5.3 ± 1.1 mmol/l; p = 0.06). Conclusions: We conclude that hypercholesterolemia is associated with calcific aortic stenosis and may be implicated in its pathogenesis and progression. We believe that there is now a need for a randomized, controlled trial of cholesterol-lowering therapy in patients with calcific aortic stenosis.