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Biomedical subjects

Daniel J Green

Publications and source records attributed to Daniel J Green.

25 records · Page 2Linked to original sources

Lack of effect of oral glucose loading on conduit vessel endothelial function in healthy subjects.

The aim of the present study was to investigate the impact of an oral glucose load on circulating insulin and glucose levels and arterial function in healthy non-diabetic subjects. Thirty-nine non-obese, healthy subjects (24 female, 15 male), aged 21.0+/-1.8 years of age, were randomly assigned to undergo either an OGTT (oral glucose tolerance test; 75 g of glucose) or administration of a placebo. Analyses of lipids, liver function and HbA(1c) (glycated haemoglobin) at baseline revealed results which were within the standard reference range. Insulin and glucose levels as well as vascular function [FMD (flow-mediated dilation)] were measured at 0, 60 and 120 min. Compared with baseline, the control subjects did not exhibit any significant changes in glucose or insulin levels, whereas, in the OGTT group, blood glucose levels at both 60 (5.4+/-1.7 mmol/l) and 120 (5.0+/-1.1 mmol/l) min increased significantly relative to baseline (4.1+/-0.4 mmol/l; both P<0.001) and, similarly, insulin levels were higher at both 60 (30.1+/-21.3 m-units/l) and 120 (34.9+/-23.6 m-units/l) min compared with baseline (4.7+/-4.3 m-units/l; both P<0.001). Although blood glucose and insulin levels changed, FMD did not significantly differ between time-points or between groups. In summary, despite significantly elevated glucose and insulin concentrations in these subjects, we observed no change in vascular function, suggesting that acute elevations of glucose and insulin within the clinically normal range are not associated with impaired vascular function in vivo.

Administration, Oral↗

Vasomotor responses to hypoxia in type 2 diabetes.

Type 2 diabetes is associated with vascular dysfunction, accelerated atherosclerotic morbidity, and mortality. Abnormal vasomotor responses to chemoreflex activation may contribute to the acceleration of atherosclerotic diabetes complications, but these responses have not previously been investigated. We measured forearm mean blood flow (MBF) and mean vascular conductance (MVC) responses to isocapnic hypoxia in seven healthy and eight type 2 diabetic subjects during local intra-arterial saline infusion and alpha-adrenergic blockade (phentolamine). The effects of hypoxia on saline and phentolamine responses significantly differed between groups; relative to normoxia, the %DeltaMVC with hypoxia during saline was -3.3 +/- 11.2% in control and 24.8 +/- 13.3% in diabetic subjects, whereas phentolamine increased hypoxic %DeltaMVC to similar levels (39.4 +/- 9.7% in control subjects and 48.0 +/- 11.8% in diabetic subjects, P < 0.05, two-way ANOVA). Absolute normoxic MBF responses during saline infusion were 91.9 +/- 21.1 and 77.9 +/- 15.3 in control and diabetic subjects, respectively, and phentolamine increased normoxic MBF to similar levels (165.2 +/- 40.1 ml/min in control subjects and 175.9 +/- 32.0 ml/min in diabetic subjects; both P < 0.05). These data indicate that diabetic and control subjects exhibit similar responses to hypoxia in the presence of alpha-adrenergic blockade despite evidence of exaggerated alpha-mediated vasoconstriction at rest.

Adrenergic alpha-Antagonists↗

Exercise-induced improvement in endothelial dysfunction is not mediated by changes in CV risk factors: pooled analysis of diverse patient populations.

We have pooled data from a series of our exercise training studies undertaken in groups with a broad range of vascular (dys) function to the examine the hypothesis that exercise-induced improvements in the conduit and/or resistance vessel function are related to improvements in risk factors for cardiovascular (CV) disease. Endothelium-dependent and -independent conduit vessel function were assessed by using wall tracking of high-resolution ultrasound images of the brachial artery response to flow-mediated dilation (FMD) and glyceryl trinitrate. Resistance vessel function was assessed using intrabrachial administration of acetylcholine (ACh), sodium nitroprusside, and NG-monomethyl-l-arginine. Randomized cross-over studies of 8-wk exercise training were undertaken in untreated hypercholesterolemic (n = 11), treated hypercholesterolemic (n = 11), coronary artery disease (n = 10), chronic heart failure (n = 12), Type 2 diabetic (n = 15), and healthy control subjects (n = 16). Exercise training did not significantly alter plasma lipids, blood pressure, blood glucose, waist-to-hip ratio, or body mass index values, despite significant improvement in both FMD and ACh responses. There were no correlations between changes in any risk factor variables and indexes of either resistance or conduit vessel function. We conclude that, in these subjects with antecedent vascular dysfunction, the beneficial effects of relatively short-term exercise training on vascular function are not solely mediated by the effects of exercise on CV risk factors.

Acetylcholine↗

Endothelial nitric oxide synthase gene polymorphism, homocysteine, cholesterol and vascular endothelial function.

Nitric oxide-dependent vasodilation is impaired early in the pathogenesis of vascular disease. Both the 4ab polymorphism of endothelial nitric oxide synthase (eNOS) and elevated plasma homocysteine are putatively associated with coronary artery disease (CAD). Few studies have investigated the influence of either on endothelial function in normal subjects. We aimed to examine any effect of three eNOS gene polymorphisms and plasma levels of homocysteine, folate and lipids on vascular endothelial function in normal healthy subjects. Community subjects (n=60) were selected for their eNOS genotype. Largely NOz.-dependent, flow-mediated dilation (FMD) of the brachial artery and the response to glyceryl trinitrate (GTN) were measured. Neither FMD nor response to GTN in 4a allele carriers was significantly different from that of 4b homozygotes, (7.1+/-0.5 S.E.M. vs. 7.1+/-0.6%) and (18.9+/-1.2 vs. 18.9+/-0.9%), respectively. Responses were also independent of the other polymorphisms. FMD was significantly correlated with HDL-cholesterol (P=0.02). After accounting for serum folate, there was a significant inverse correlation between FMD and plasma homocysteine (P=0.03). In these normal community subjects, plasma homocysteine and HDL-cholesterol were predictors of FMD despite subjects being recruited without regard to these variables and despite normal plasma levels.

Adult↗

Effects of exercise training on conduit and resistance vessel function in treated and untreated hypercholesterolaemic subjects.

AIMS: Despite the importance of both lipid metabolism and physical activity to cardiovascular health, few studies have examined the effect of exercise training on vascular function in hypercholesterolaemic humans. METHODS AND RESULTS: A randomized, cross-over design investigated the effect of 8 weeks of combined aerobic and resistance exercise training on conduit and resistance vessel function in 11 untreated subjects with hypercholesterolaemia and 11 subjects taking lipid-lowering medication. High-resolution vascular ultrasonography following forearm ischaemia and glyceryl trinitrate administration determined conduit vessel endothelium-dependent and independent function. Strain-gauge plethysmography, with intra-aerial infusions of acetylcholine, sodium nitroprusside and N(G)-monomethyl-L-arginine, determined resistance vessel function. Flow-mediated dilation and the forearm blood flow response to acetylcholine improved significantly following training in the treated subgroup (both P<0.05) but not the untreated, although the blood flow response to N(G)-monomethyl-L-arginine was augmented following training in the untreated subjects (P<0.05), indicating greater basal nitric oxide bioactivity. Training did not alter responsiveness to glyceryl trinitrate or sodium nitroprusside. CONCLUSIONS: Combined aerobic and resistance training improves endothelium-dependent conduit and resistance vessel function in hypercholesterolaemic subjects taking lipid-lowering medications and basal nitric oxide bioactivity in untreated hypercholesterolaemic subjects. Exercise training may provide additional cardiovascular benefits for hypercholesterolaemic patients including those taking lipid-lowering medication.

Cholesterol↗

Exercise training improves conduit vessel function in patients with coronary artery disease.

It is well established that endothelial dysfunction is present in coronary artery disease (CAD), although few studies have determined the effect of training on peripheral conduit vessel function in patients with CAD. A randomized, crossover design determined the effect of 8 wk of predominantly lower limb, combined aerobic and resistance training, in 10 patients with treated CAD. Endothelium-dependent dilation of the brachial artery was determined, by using high-resolution vascular ultrasonography, from flow-mediated vasodilation (FMD) after ischemia. Endothelium-independent vasodilation was measured after administration of glyceryl trinitrate (GTN). Baseline function was compared with that of 10 control subjects. Compared with matched healthy control subjects, FMD and GTN responses were significantly impaired in the untrained CAD patients [3.0 +/- 0.8 (SE) vs. 5.8 +/- 0.8% and 14.5 +/- 1.9 vs. 20.4 +/- 1.5%, respectively; both P < 0.05]. Training significantly improved FMD in the CAD patients (from 3.0 +/- 0.8 to 5.7 +/- 1.1%; P < 0.05) but not responsiveness to GTN (14.5 +/- 1.9 vs. 12.1 +/- 1.4%; P = not significant). Exercise training improves endothelium-dependent conduit vessel dilation in subjects with CAD, and the effect, evident in the brachial artery, appears to be generalized rather than limited to vessels of exercising muscle beds. These results provide evidence for the benefit of exercise training, as an adjunct to routine therapy, in patients with a history of CAD.

Brachial Artery↗