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David J Webb

Publications and source records attributed to David J Webb.

95 records · Page 6Linked to original sources
PubMed2002

Pulse-wave analysis: clinical evaluation of a noninvasive, widely applicable method for assessing endothelial function.

Current methods for assessing vasomotor endothelial function are impractical for use in large studies. We tested the hypothesis that pulse-wave analysis (PWA) combined with provocative pharmacological testing might provide an alternative method. Radial artery waveforms were recorded and augmentation index (AIx) was calculated from derived aortic waveforms. Thirteen subjects received sublingual nitroglycerin (NTG), inhaled albuterol, or placebo. Twelve subjects received NTG, albuterol, and placebo separately during an infusion of N(G)-monomethyl-L-arginine (LNMMA) or norepinephrine. Twenty-seven hypercholesterolemic subjects and 27 controls received NTG followed by albuterol. Endothelial function was assessed by PWA and forearm blood flow in 27 subjects. Albuterol and NTG both significantly and repeatably reduced AIx (P<0.001). Only the response to albuterol was inhibited by LNMMA (-9.8+/-5.5% vs -4.7+/-2.7%; P=0.02). Baseline AIx was higher in the hypercholesterolemic subjects, who exhibited a reduced response to albuterol (P=0.02) but not to NTG when compared with matched controls. The responses to albuterol and acetylcholine were correlated (r=0.5, P=0.02). Consistent with an endothelium-dependent effect, the response to albuterol was substantially inhibited by LNMMA. Importantly, the response to albuterol was reduced in subjects with hypercholesterolemia and was correlated to that of intra-arterial acetylcholine. This methodology provides a simple, repeatable, noninvasive means of assessing endothelial function in vivo.

Acetylcholine↗
PubMed2002

Peripheral vascular structure and function in men with contrasting GH levels.

Both GH deficiency and excess are associated with cardiovascular disease. The mechanisms are unclear, but direct effects of GH in the vessel wall may be important. Previous reports suggest that GH enhances endothelium-dependent vasodilatation and alters large artery structure. Here we report a detailed assessment of large artery and microvascular structure and function in patients with contrasting GH levels. We studied six age-matched healthy control men, five men with acromegaly, and seven men with adult-onset GH deficiency before and at the end of 16 wk of GH replacement therapy. We measured arterial wall thickness by ultrasound of the common carotid artery; arterial stiffness by pulse wave analysis at the radial artery; microvascular structure by measurement of flow during maximal dilatation in the forearm and dermal circulation and counting dermal capillaries using video microscopy; and endothelial function in the forearm during brachial artery infusion of vasodilators (acetylcholine and sodium nitroprusside). Cardiac output was measured by Doppler ultrasound in GH-deficient patients and controls. GH-deficient patients tended to have increased arterial wall thickness and arterial stiffness, compared with controls. GH replacement reduced arterial stiffness (radial augmentation index 0.28 +/- 0.07 to 0.20 +/- 0.12, P = 0.02) and increased the number of dermal capillaries perfused (28.6 +/- 5.0 to 30.9 +/- 6.5 cm(-2), P = 0.03), but a reduction in arterial wall thickness was not statistically significant. With respect to maximum flow in forearm and dermis and endothelial function, GH-deficient patients were not different from controls, and GH therapy had no effect. Moreover, acromegalic patients were not different from controls in any vascular parameters studied. We conclude that the direct vascular effects of GH excess and deficiency in man are of modest magnitude and should not therefore be given the highest priority in considering the risks of cardiovascular events in patients with pituitary disease.

Acromegaly↗
PubMed2002

Nitric oxide donor drugs: current status and future trends.

Nitric oxide synthesised in endothelial cells that line blood vessels has a wide range of functions that are vital for maintaining a healthy cardiovascular system. Reduced nitric oxide availability is implicated in the initiation and progression of many cardiovascular diseases and delivery of supplementary nitric oxide to help prevent disease progression is an attractive therapeutic option. Nitric oxide donor drugs represent a useful means of systemic nitric oxide delivery and organic nitrates have been used for many years as effective therapies for symptomatic relief from angina. However, nitrates have limitations and a number of alternative nitric oxide donor classes have emerged since the discovery that nitric oxide is a crucial biological mediator. This review focuses on novel advances and possible future directions in nitric oxide donor drug development.

Cardiovascular Diseases↗