Christopher J Lockhart | Search PubMed

PubMed2006

Measuring endothelial function.

Dysfunction of the endothelium and of the arterial wall is well described in patients with atherosclerosis, diabetes, and other risk factors for vascular disease. In recent years, clinical research has focused on elucidating the role of this dysfunction in influencing vascular disease progression. Alteration in the structure of arteries and disruption of the homeostatic functions of the endothelium act as a substrate for end-organ damage and the occurrence of vascular events. Dysfunction of the vascular endothelial cells is probably the earliest event promoting atherosclerotic lesion formation. Therefore, methods capable of assessing endothelial function at a preclinical stage hold potential to refine cardiovascular risk stratification and serve as a guide to monitor the effects of therapeutic interventions. A number of methodologies are currently employed to assess endothelial function, but the optimal approach is not firmly established. In this article, we critically appraise the use of different methodologies employed to study endothelial function as a surrogate marker of future cardiovascular risk.

Blood Flow Velocity↗

PubMed2006

Nitric oxide modulation of ophthalmic artery blood flow velocity waveform morphology in healthy volunteers.

Quantitative analysis of the arterial pressure pulse waveform recorded by applanation tonometry of the radial artery can track NO (nitric oxide)-mediated modulation of arterial smooth muscle tone. The changes in pressure pulse waveform morphology result from pulse wave reflection arising predominantly from smaller arteries and arterioles. Employing Doppler ultrasound to record the spectral flow velocity waveform in the ophthalmic artery, we studied the effects of NO modulation on waveforms recorded in the proximity of the terminal ocular microcirculatory bed. In healthy young men (n=10; age 18-26 years), recordings were made at baseline, following 300 mug of sublingual GTN (glyceryl trinitrate) and during the intravenous infusion of 0.25 and 0.5 mg/kg of L-NAME (N(G)-nitro-L-arginine methyl ester). Peaks (P1, P2 and P3) and nodes (N1, N2 and N3) on the arterial flow velocity waveform were identified during the cardiac cycle and employed to quantify wave shape change in response to the haemodynamic actions of the pharmacological interventions. The administration of GTN resulted in a significant (P<0.05) increase in heart rate without significant alteration in blood pressure. At the doses employed, L-NAME did not significantly alter systemic haemodynamics. With the exception of peak Doppler systolic velocity, all other peaks and nodes decreased significantly in response to GTN (P<0.05 for all points compared with baseline). In response to the administration of L-NAME, all peaks and nodes decreased significantly (P<0.05 for all points compared with baseline). The resistive index, a ratio calculated from the peak and trough flow velocities employed to assess change in flow resistance, increased significantly in response to GTN (0.77 at baseline compared with 0.85; P<0.05). Quantification of changes in the flow velocity spectral waveform during the cardiac cycle sensitively identified NO modulation of smooth muscle tone prior to alteration in systemic haemodynamics. Focusing on the resistive index, which identifies isolated points on the waveform describing the excursions of flow, may provide misleading information in relation to the haemodynamic effects of drug interventions.

Adolescent↗