PubMed Health⌕ Search

Biomedical subjects

I B Wilkinson

Publications and source records attributed to I B Wilkinson.

At least 19 recordsLinked to original sources
PubMed2005

The effect of exercise on large artery haemodynamics in healthy young men.

BACKGROUND: Brachial blood pressure predicts cardiovascular outcome at rest and during exercise. However, because of pulse pressure amplification, there is a marked difference between brachial pressure and central (aortic) pressure. Although central pressure is likely to have greater clinical importance, very little data exist regarding the central haemodynamic response to exercise. The aim of the present study was to determine the central and peripheral haemodynamic response to incremental aerobic exercise. MATERIALS AND METHODS: Twelve healthy men aged 31 +/- 1 years (mean +/- SEM) exercised at 50%, 60%, 70% and 80% of their maximal heart rate (HRmax) on a bicycle ergometer. Central blood pressure and estimated aortic pulse wave velocity, assessed by timing of the reflected wave (T(R)), were obtained noninvasively using pulse wave analysis. Pulse pressure amplification was defined as the ratio of peripheral to central pulse pressure and, to assess the influence of wave reflection on amplification, the ratio of peripheral pulse pressure to nonaugmented central pulse pressure (PPP : CDBP-P1) was also calculated. RESULTS: During exercise, there was a significant, intensity-related, increase in mean arterial pressure and heart rate (P < 0.001). There was also a significant increase in pulse pressure amplification and in PPP : CDBP-P(1) (P < 0.001), but both were independent of exercise intensity. Estimated aortic pulse wave velocity increased during exercise (P < 0.001), indicating increased aortic stiffness. There was also a positive association between aortic pulse wave velocity and mean arterial pressure (r = 0.54; P < 0.001). CONCLUSIONS: Exercise significantly increases pulse pressure amplification and estimated aortic stiffness.

Adult↗
PubMed2004

Infliximab improves endothelial dysfunction in systemic vasculitis: a model of vascular inflammation.

BACKGROUND: Endothelial vasomotor dysfunction and markers of systemic inflammation are independent determinants of cardiovascular risk. However, the link between clinical inflammation and endothelial dysfunction is unclear. The aim of this study was to use anti-neutrophil cytoplasmic antibody-associated systemic vasculitis (AASV) as a model of systemic inflammation in which to test the hypothesis that inflammation is associated with endothelial dysfunction and can be reversed with anti-tumor necrosis factor-alpha (TNF-alpha) therapy. METHODS AND RESULTS: Fourteen patients with active AASV and 21 age-matched control subjects were studied. Endothelial function was assessed through the use of forearm plethysmography and related to clinical disease activity: Birmingham Vasculitis Activity Score (BVAS) and serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and TNF-alpha. The effects of anti-TNF-alpha therapy (infliximab), either alone (n=6) or in combination with standard treatment (n=4), on endothelial function were subsequently determined. Patients had a mean BVAS of 11+/-1, and CRP and IL-6 were higher in the AASV group than in control subjects (34.8+/-10.5 versus 1.6+/-0.2 pg/mL, P<0.001; 9.0+/-0.7 versus 6.7+/-0.6 pg/mL, P=0.02). Forearm blood flow response to acetylcholine (ACh) was reduced in the patients compared with control subjects (P=0.002), but sodium nitroprusside (SNP) responses were not (P=0.3). The response to ACh improved with infliximab treatment (P=0.004) in particular, with infliximab alone (P=0.03). CONCLUSIONS: AASV is associated with endothelial dysfunction. Anti-TNF-alpha therapy, alone or in combination with standard treatment, results in clinical remission, reduced inflammation, and improved endothelium-dependent vasomotor responses.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Inflammation and arterial stiffness in systemic vasculitis: a model of vascular inflammation.

OBJECTIVE: Arterial stiffness, an independent determinant of cardiovascular risk, is regulated by both structural and functional factors, including endothelium-derived nitric oxide. Endothelial dysfunction is associated with acute and chronic systemic inflammation. However, the role of systemic inflammation in arterial stiffening has not been determined. The aim of this study was to investigate the relationship between inflammation and arterial stiffness in patients with antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV) as a model of systemic inflammation. METHODS: Thirty-one patients with AASV (15 with active disease) and 32 age-matched controls were studied. Pulse wave velocity (PWV) and the augmentation index (AIx) were assessed noninvasively and related to serum levels of C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha. RESULTS: In subjects with active disease, the AIx, PWV, and level of CRP were elevated compared with that in controls (mean +/- SEM 31 +/- 3% versus 22 +/- 2% [P = 0.003], 9.2 +/- 0.7 versus 7.5 +/- 0.3 meters/second [P = 0.03], and 16.0 +/- 4.0 versus 1.1 +/- 0.1 mg/liter [P < 0.001], respectively). However, PWV and the AIx were not significantly different between patients with disease in remission and controls (8.0 +/- 0.5 versus 7.5 +/- 0.3 meters/second and 19 +/- 3% versus 22 +/- 2%, respectively). The CRP level was positively correlated with both PWV and the AIx. Multiple regression analysis indicated that age, mean arterial pressure (MAP), and CRP were independently related to PWV, and that age, MAP, CRP, sex, and heart rate were associated with the AIx. CONCLUSION: These data indicate that AASV is associated with increased arterial stiffness, and that stiffness correlates with the degree of active inflammation.

Adolescent↗
PubMed2001

Pressure amplification explains why pulse pressure is unrelated to risk in young subjects.

Pulse pressure rather than diastolic pressure is the best predictor of coronary heart disease risk in older subjects, but the converse is true in younger subjects. We hypothesized that this disparity results from an age-related difference in pressure amplification from the aorta to brachial artery. Data from 212 subjects age < 50 years and 230 subjects age > or =50 years were abstracted from a community database. All subjects were free from cardiovascular disease, diabetes, and medication. Peripheral blood pressure was assessed by sphygmomanometry. Radial artery waveforms recorded noninvasively by applanation tonometry were used to derive central blood pressure. Pressure amplification (peripheral/central pulse pressure ratio) was linearly related to age (r=0.7; P<0.001). There was an inverse, linear relationship between amplification and diastolic pressure in the younger group (r=0.3; P<0.001) but not in older subjects (r=0.1; P=0.2). There was no relationship in either group when the amplification ratio was calculated with nonaugmented central pressure. Amplification is reduced in older subjects because of enhanced wave reflection. In younger, but not older, subjects, amplification declines as diastolic pressure rises. Therefore, peripheral pulse pressure underestimates the effect that diastolic pressure has on central pulse pressure in younger subjects. This may explain why diastolic pressure is a better predictor of risk in this age group and suggests that assessment of central pressure may improve risk stratification further.

Adult↗
PubMed2001

Changes in the derived central pressure waveform and pulse pressure in response to angiotensin II and noradrenaline in man.

Peripheral pulse pressure provides a surrogate measure of arterial stiffness. Analysis of the central pressure waveform allows assessment of central pulse pressure and arterial stiffness. The aim of the present study was to assess the effect of vasoconstrictor drugs on pulse pressure amplification and arterial stiffness in vivo. Eight healthy male subjects (mean age 30 years) received an infusion of angiotensin II (1, 3, 6 and 10 ng kg(-1) min(-1)), noradrenaline (10, 30, 60 and 100 ng kg(-1) min(-1)) and matching placebo, in random order, on separate occasions. Peripheral blood pressure and cardiac index were recorded non-invasively. Pulse wave analysis was used to determine augmentation index (AIx), which provides a measure of systemic arterial stiffness, aortic stiffness and central arterial pressure. Infusion of both active drugs resulted in a significant increase in peripheral mean arterial pressure (PMAP), peripheral vascular resistance, AIx, aortic stiffness and central pulse pressure, but only angiotensin II reduced cardiac index. Peripheral pulse pressure was unaffected by infusion of angiotensin II but increased with noradrenaline, which also produced a greater reduction in pulse pressure amplification than angiotensin II. However, the linear relationship of PMAP with both AIx and aortic stiffness did not differ significantly between drugs. These results demonstrate that intravenous infusion of angiotensin II and noradrenaline increase aortic and systemic arterial stiffness. Despite a similar effect on both parameters, for a given change in PMAP, the two drugs had divergent effects on peripheral pulse pressure and pulse pressure amplification. These data reveal that assessment of peripheral pulse pressure does not always reliably predict changes in central pulse pressure or arterial stiffness.

Adult↗
PubMed2001

Adrenomedullin (ADM) in the human forearm vascular bed: effect of neutral endopeptidase inhibition and comparison with proadrenomedullin NH2-terminal 20 peptide (PAMP).

AIMS: To compare the haemodynamic responses of proadrenomedullin N-terminal 20 peptide (PAMP) and adrenomedullin (ADM) in the forearm vascular bed of healthy male volunteers, and to investigate the role of neutral endopeptidase (NEP) in the metabolism of ADM. METHODS: On two separate occasions, ADM (1-30 pmol x min(-1)) and PAMP (100-3000 pmol x min(-1)) were infused into the brachial artery of eight male subjects, and forearm blood flow (FBF) assessed using venous occlusion plethysmography. In a second study, eight male subjects received the same doses of ADM, co-infused with either the NEP inhibitor thiorphan (30 nmol x min(-1)) or the control vasoconstrictor noradrenaline (120 pmol x min(-1)), on separate occasions. Both studies were conducted in a double-blind, randomized manner. RESULTS: ADM and PAMP produced a dose-dependent increase in FBF (P < or = 0.002). Based on the dose producing a 50% increase in FBF, ADM was approximately 60 times more potent than PAMP. Thiorphan and noradrenaline produced similar reductions in FBF of 14 +/- 4% (mean +/- s.e. mean) and 22 +/- 6%, respectively (P = 0.4). However, the area under the dose-response curve was significantly greater during co-infusion of ADM with thiorphan than with noradrenaline (P = 0.028), as was the maximum increase in FBF ratio (2.1 +/- 1.0 vs 1.2 +/- 0.2; P = 0.030). CONCLUSIONS: ADM and PAMP both produce a local dose-related vasodilatation in the human forearm, but PAMP is approximately 60 times less potent than ADM. In addition, NEP inhibition potentiates the haemodynamic effects of ADM. These findings suggest that PAMP may not play a role in the physiological regulation of blood flow. However, in pathophysiological conditions such as hypertension and heart failure, NEP inhibition may exert a beneficial effect by increasing the biological activity of ADM.

Adrenomedullin↗
PubMed2001

Comparison of brachial artery pressure and derived central pressure in the measurement of abdominal aortic aneurysm distensibility.

OBJECTIVE: AAA distensibility (Ep, beta) may predict growth and risk of rupture. However, distensibility measurements based on brachial rather than central pressure may be inaccurate. Our aim was to compare AAA distensibility using non-invasive brachial and derived central aortic pressure. DESIGN: brachial and central pressures were measured prospectively by automated sphygmomanometry (Omron) and pulse wave analysis (SphygmoCor) respectively. AAA distensibility was calculated using brachial (Ep(b), beta(b)) and central (Ep(c), beta(c)) pressures by ultrasonic echo-tracking (Diamove). Twenty-eight patients (18 males) were selected on a first come basis from a larger study of AAA patients. There were no exclusion criteria, so 54% had cardiac dysfunction (MI, angina) and 14% were hypertensive (BP >140/90 mmHg). RESULTS: median (IQR) age was 74 (70-77) years, median AAA (IQR) diameter was 44 (40-51) mm. Central and brachial systolic pressures were significantly different, [140 (121-153) vs 144 (130-164) mmHg respectively, p < or =0.01]. Central and brachial diastolic pressures were not significantly different [76 (72-86) vs 76 (71-86) mmHg respectively, p=0.5]. Ep(c)(3.0, [2.2-4.9]) and beta(c)(22.2 [15.5-33.2]) were significantly lower than Ep(b)(3.6, [2.4-5.1] 10(5)Nm(-2)) and beta(b)(24.7 [17.1-33.0] a.u., all p < 0.001. Brachial and central derived distensibility remained significantly different after adjusting for age and diameter (p<0.001). CONCLUSION: the use of brachial pressure leads to a small, systematic overestimate of Ep (18%) and beta (11%) independent of age and AAA diameter. This systematic error will not bias follow-up of changes in distensibility.

Aged↗
PubMed2001

Acute methionine loading does not alter arterial stiffness in humans.

Hyperhomocystinemia is a risk factor for cardiovascular disease, and acute elevation of plasma homocysteine after methionine loading impairs endothelial function in healthy subjects. Interestingly, pretreatment with vitamin C can ameliorate this effect. We have already shown that acute oral vitamin C administration reduces arterial stiffness in healthy subjects, and the aim of the present study was to investigate the effect of methionine loading on arterial stiffness with and without concomitant vitamin C using the noninvasive technique of pulse wave analysis. Eight healthy male subjects (mean age, 29 years; range, 20-42 years) were studied on three occasions at weekly intervals. In a double-blind, double-dummy, randomized order they received orally either 100 mg/kg methionine, 100 mg/kg methionine plus 2 g of vitamin C, or matching placebos. Peripheral and central blood pressure, heart rate, cardiac index, arterial stiffness, and plasma homocysteine levels were assessed at baseline and 6 hours after dosing. Compared with placebo, there was no significant change in any of the hemodynamic parameters, including arterial stiffness, after oral methionine, although plasma homocysteine did increase from 11.5 +/- 1.6 to 28.7 +/- 4.4 microM (mean +/- SEM; p < 0.001). Combined methionine and vitamin C led to a similar increase in plasma homocysteine but significantly reduced augmentation index by 10.5 +/- 3.2% (p = 0.02). Acute hyperhomocystinemia does not significantly alter arterial stiffness, as assessed by pulse wave analysis, whereas a combination of methionine and vitamin C leads to a similar reduction in augmentation index to that previously described after vitamin C alone. These data reinforce evidence that vitamin C reduces arterial stiffness but do not indicate any important interaction with oral methionine.

Adult↗
PubMed2001

Effects of acute methionine loading and vitamin C on endogenous fibrinolysis, endothelium-dependent vasomotion and platelet aggregation.

We assessed forearm blood flow and plasma fibrinolytic factors in eight healthy males who received unilateral brachial artery infusions of the endothelium-dependent vasodilator, substance P, and the endothelium-independent vasodilator, sodium nitroprusside. These measurements, together with platelet aggregation studies, were performed on four occasions after double-blind randomized ingestion of placebo, methionine (0.1 mg/kg), vitamin C (2 g) and methionine plus vitamin C. Blood flow and platelet aggregation responses were unaffected by methionine loading. Substance P caused dose-dependent increases in plasma tissue plasminogen activator (t-PA) antigen (from 3.0+/-0.1 to 4.7+/-0.4 ng/ml; P<0.001) and activity (from 1.2+/-0.2 to 4.2+/-0.4 i.u./ml; P<0.001), which were augmented during acute methionine loading (4.7+/-0.4 to 5.6+/-0.5 ng/ml and 4.2+/-0.4 to 5.5+/-0.9 i.u./ml respectively; P</=0.05). Moreover, the estimated net release of t-PA was enhanced during methionine loading (two-way ANOVA; P=0.02), but this was unaffected by vitamin C supplementation. We conclude that, in the absence of alterations in endothelium-dependent vasomotion or platelet aggregation, substance P-induced t-PA release is enhanced following methionine loading. This suggests that the acute endogenous fibrinolytic capacity is augmented during acute hyperhomocysteinaemia in healthy humans via an oxidation-independent mechanism.

Acute Disease↗
PubMed2000

The influence of heart rate on augmentation index and central arterial pressure in humans.

Arterial stiffness is an important determinant of cardiovascular risk. Augmentation index (AIx) is a measure of systemic arterial stiffness derived from the ascending aortic pressure waveform. The aim of the present study was to assess the effect of heart rate on AIx. We elected to use cardiac pacing rather than chronotropic drugs to minimize confounding effects on the systemic circulation and myocardial contractility. Twenty-two subjects (13 male) with a mean age of 63 years and permanent cardiac pacemakers in situ were studied. Pulse wave analysis was used to determine central arterial pressure waveforms, non-invasively, during incremental pacing (from 60 to 110 beats min-1), from which AIx and central blood pressure were calculated. Peripheral blood pressure was recorded non-invasively from the brachial artery. There was a significant, inverse, linear relationship between AIx and heart rate (r = -0.76; P < 0.001). For a 10 beats min-1 increment, AIx fell by around 4 %. Ejection duration and heart rate were also inversely related (r = -0. 51; P < 0.001). Peripheral systolic, diastolic and mean arterial pressure increased significantly during incremental pacing. Although central diastolic pressure increased significantly with pacing, central systolic pressure did not. There was a significant increase in the ratio of peripheral to central pulse pressure (P < 0.001), which was accounted for by the observed change in central pressure augmentation. These results demonstrate an inverse, linear relationship between AIx and heart rate. This is likely to be due to alterations in the timing of the reflected pressure wave, produced by changes in the absolute duration of systole. Consideration of wave reflection and aortic pressure augmentation may explain the lack of rise in central systolic pressure during incremental pacing despite an increase in peripheral pressure.

Age Factors↗