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Biomedical subjects

I T Meredith

Publications and source records attributed to I T Meredith.

At least 37 records · Page 2Linked to original sources
PubMed2000

Basal and exercise-induced skeletal muscle blood flow is augmented in type I diabetes mellitus.

Hyperaemia occurs early in the renal and retinal microcirculation of patients with type I (insulin-dependent) diabetes mellitus, and may be critical in the development of nephropathy and retinopathy. We therefore sought to determine whether resting and exercise-induced hyperaemia was also apparent in the skeletal muscle circulation of young subjects with type I diabetes. Blood flow was assessed by venous occlusion plethysmography in 18 diabetic (DM) subjects and 20 matched controls. Exercise entailed 2 min of isotonic exercise against no load. Endothelium-dependent and -independent vasodilator function was assessed following intra-arterial infusion of acetylcholine and sodium nitroprusside respectively. Forearm blood flow (FBF) was higher in DM subjects than in controls (3.3+/-0.3 and 2.2+/-0.2 ml x min(-1) x 100 ml(-1) forearm respectively; P<0.005). This was not due to differences in forearm or body size, blood pressure, heart rate, lipid status or glycaemic control. Peripheral insulin levels were higher in DM subjects than in controls (48.5+/-8 and 15.5+/-1.5 micro-units/ml respectively; P<0.005). Resting FBF was closely correlated with insulin levels (r(2)=0.4; P<0.005). Parameters of exercise-induced hyperaemia [including peak flow (16.4+/-1.4 and 12.0+/-0.7 ml x min(-1) x 100 ml(-1) forearm in DM and control subjects respectively; P<0.01) and the volume repaid to the forearm at 5 min post-exercise (32.1+/-3.1 and 23.1+/-1.4 ml x 100 ml(-1) forearm respectively; P<0.05)] were also significantly greater in DM subjects, even when differences in resting FBF were taken into account. Peak hyperaemic blood flow and the volume repaid at 5 min were also related to insulin levels (r(2)=0.16; P<0.05 and r(2)=0.27; P<0.005 respectively). The vasodilator response to acetylcholine was reduced in DM subjects (P<0.05; analysis of variance), and the slope of this dose-flow relationship was inversely related to insulin levels (r(2)=0.2; P<0.05). These data show that both resting and exercise-induced skeletal muscle blood flow are augmented in young patients with type I diabetes, possibly due to the vasodilatory effect of increased insulin levels. Diminished vasodilator responses to acetylcholine may also, in part, be a consequence of insulin-augmented resting muscle blood flow.

Acetylcholine↗
PubMed2000

Occlusion cuff position is an important determinant of the time course and magnitude of human brachial artery flow-mediated dilation.

Non-invasive ultrasound techniques to assess flow-mediated vasodilation (FMD) are frequently used to assess arterial endothelial vasodilator function. However, the range of normal values varies considerably, possibly due to differences in methodological factors. We sought to determine the effect of occlusion cuff position on the time course and magnitude of brachial artery blood flow and flow-mediated dilation. Twelve healthy subjects underwent measurements of forearm blood flow using venous occlusion plethysmography (VOP) before and after 5 min of susprasystolic cuff inflation, using two randomly assigned occlusion cuff positions (upper arm and forearm). An additional 16 subjects underwent two brachial ultrasound studies, using the two cuff positions, to assess the extent and time course of changes in brachial artery diameter and blood flow. Maximum increase in blood flow (peak reactive hyperaemia), measured by VOP, occurred immediately upon each cuff deflation, but was greater after upper arm compared with forearm arterial occlusion (33.1+/-3.1 versus 22.8+/-2.2 ml/min per forearm tissue, P=0.001). Maximal brachial artery FMD was significantly greater following upper arm occlusion (9.0+/-1.2%, mean +/- S.E.M.) compared with forearm occlusion (5.9+/-0.7%, P=0.01). The time course of the change in brachial artery diameter was affected differently in response to each protocol. The time to peak dilation following upper arm occlusion was delayed by 22 s compared with forearm occlusion. Occlusion cuff position is thus a powerful determinant of peak reactive hyperaemia, volume repaid and the extent and time course of brachial artery FMD. Positioning the cuff on the upper arm produces a greater FMD. These results highlight the need for comparisons between FMD studies to be made with care.

Adult↗
PubMed2000

Percutaneous coronary intervention in the elderly: a comparison of procedural and clinical outcomes between the eighth and ninth decades.

AIMS: To compare short-term safety and outcome of percutaneous coronary intervention (PCI) in the elderly in their ninth decade with those in their eighth decade. METHODS: Five-hundred and eighty-nine patients aged 70 years undergoing coronary angioplasty were stratified into two groups, those 80 years old (Group 1, n = 65) and those 70Eth 79 years old (Group 2, n = 524). RESULTS: Group 1 comprised more females than Group 2 (57% vs. 40%, respectively; p = 0.009), patients with hypertension (70% vs. 56%, respectively), untreated hyperlipidemia (18% vs. 7%, respectively), acute coronary syndromes (75% vs. 53%, respectively) and multi-vessel disease (63% vs. 54%, respectively). Angiographic success per lesion was similar in Groups 1 and 2 (96% vs. 99%, respectively) as was clinical success per lesion (89% vs. 89%, respectively). Groups 1 and 2 also had a similar incidence of in-hospital death (1.5% vs. 1.1%, respectively), Q-wave myocardial infarction (0.0% vs. 0.6%, respectively), non-Q wave myocardial infarction (6.2% vs. 2.9%, respectively), emergency coronary artery bypass surgery (0.0% vs. 1. 3%, respectively), repeat PCI (3.0% vs. 1.7%, respectively), stroke (1.5% vs. 0.4%, respectively) and local vascular complications (4.6% vs. 4.4%, respectively). However, Group 1 had a longer in-hospital stay (4 days) than Group 2 (2 days) (p < 0.001). CONCLUSION: Our data suggest that short-term procedural and clinical outcomes after PCI are similar for patients in their eighth decade compared to those in their ninth decade.

Age Factors↗
PubMed2000

Vasodilator prostanoids, but not nitric oxide, may account for skeletal muscle hyperaemia in Type I diabetes mellitus.

We and others have previously documented increased resting and exercise-induced skeletal muscle blood flow in young subjects with Type I (insulin-dependent) diabetes mellitus compared with healthy controls. Both NO and prostanoids are important regulators of vascular tone and may therefore contribute to this hyperaemia. The aim of the present study was to determine the contribution of NO and vasodilator prostanoids to this skeletal muscle hyperaemia in diabetes. We assessed the effects of infusion into the intrabrachial artery of the cyclo-oxygenase inhibitor acetylsalicylic acid (ASA; aspirin) and of the L-arginine analogue N(G)-monomethyl-L-arginine (L-NMMA) on skeLetal muscle blood flow in subjects with Type I diabetes mellitus (DM subjects) and control subjects. Blood flow was measured by venous occlusion plethysmography. Isotonic forearm exercise involved 2 min of wrist flexion and extension. Resting flow (forearm blood flow; FBF) was augmented in DM subjects, as was peak exercise-related blood flow (PFBF) and the volume repaid to the forearm 5 min after exercise (AUC 5, where AUC is area under the flow-time curve) (P<0.05), even when accounting for differences in basal flow. Infusion of L-NMMA reduced resting flow by 48% in controls (P<0.005) and by 12% in DM subjects (not significant). L-NMMA reduced PFBF and AUC 5 by 29% (P<0.05) and 39% (P<0.0005) respectively in controls, but had no significant effect on these parameters in DM subjects. Infusion of ASA reduced FBF, PFBF and AUC 5 in both DM (P<0.05) and control (P<0.05) subjects, but the magnitude of this reduction was greater in DM than in control subjects (ANOVA, P<0.05), even when differences in resting FBF were accounted for. Indeed, ASA eliminated the differences in FBF, PFBF and AUC 5 between DM and control subjects. Thus increased release of vasodilator prostanoids, rather than of NO, appears to account for skeletal muscle hyperaemia in Type I diabetes.

Adult↗
PubMed1999

Contribution of vasodilator prostanoids and nitric oxide to resting flow, metabolic vasodilation, and flow-mediated dilation in human coronary circulation.

BACKGROUND: Endothelial dysfunction is associated with atherosclerosis and may contribute to ischemic syndromes. We assessed the contribution of endothelium-derived nitric oxide (NO) and vasodilator prostanoids to resting blood flow, metabolic vasodilation, and flow reserve in the human coronary circulation. METHODS AND RESULTS: Coronary hemodynamics were assessed before and after inhibition of vasodilator prostanoids and NO with intracoronary aspirin (acetylsalicylic acid [ASA]) and N(G)-monomethyl-L-arginine (L-NMMA), respectively. Angiographically smooth or mildly irregular vessels, with normal adenosine-induced coronary flow reserve, were studied in 25 patients undergoing clinically indicated procedures. Coronary blood velocity was measured by Doppler flow wire, and coronary blood flow (CBF) was calculated. ASA reduced resting conduit vessel diameter by 11% (P = 0.003) and CBF by 27% (P = 0.008) and increased coronary vascular resistance (CVR) by 24% (P<0.0001). ASA attenuated pacing-induced hyperemia by 28% (45.0+/-4.6 versus 32.6+/-3.4 mL/min, P = 0.005) and increased minimum CVR by 39% (2.8+/-0.3 versus 3.9+/-0.5 mm Hg x mL(-1) x min(-1), P = 0.007). L-NMMA reduced resting conduit vessel diameter by 9% (P = 0.05) and CBF by 20% (P = 0.08) and increased CVR by 19% (P = 0.03). L-NMMA attenuated pacing-induced hyperemia by 20% (42.4+/-5.1 versus 34.1+/-3.4 mL/min, P = 0.04) and increased minimum CVR by 33% (2.9+/-0.4 versus 3.8+/-0.5 mm Hg x mL(-1) x min(-1), P = 0.02). ASA (7.7+/-2.3% versus -1.6+/-3.2%, P = 0.06) and L-NMMA (12.1+/-3.9% versus 0.0+/-2.9%, P = 0.02) abolished pacing-induced conduit vessel flow-mediated dilation. Conclusions-Tonic release of vasodilator prostanoids and NO contributes to resting conduit and resistance vessel tone and to peak functional hyperemia and flow-mediated dilation after metabolic stimulation. This underscores the importance of normal endothelial function for metabolic vasodilation and suggests that it may be a key mechanism for preventing myocardial ischemia in coronary artery disease.

Adenosine↗
PubMed1999

Metabolic vasodilation in the human forearm is preserved in hypercholesterolemia despite impairment of endothelium-dependent and independent vasodilation.

OBJECTIVE: Hypercholesterolemia has been shown to impair endothelium-mediated, nitric oxide (NO)-dependent responses to acetylcholine (ACh), serotonin, substance P and flow-mediated dilation. We have recently shown that NO contributes to metabolic vasodilation in the human forearm. We sought to determine whether metabolic vasodilation is impaired in healthy subjects with hypercholesterolemia. METHODS: We compared the forearm blood flow (FBF) responses to isotonic exercise, ACh and the endothelium-independent vasodilator sodium nitroprusside in young, otherwise healthy volunteers with hypercholesterolemia and controls before and after the NO inhibitor NG-monomethyl-L-arginine (L-NMMA). FBF was measured using venous occlusion plethysmography. Hypercholesterolemic (n = 20) and control (n = 20) subjects were age- and gender-matched. RESULTS: Total cholesterol (6.9 +/- 0.3 vs. 4.6 +/- 0.1 mmol/l, P < 0.0001), low density lipoprotein (4.9 +/- 0.4 vs. 2.7 +/- 0.1 mmol/l, P < 0.001) and triglyceride (1.3 +/- 0.2 vs. 0.8 +/- 0.1 mmol/l, P = 0.005) levels were higher in the hypercholesterolemic group. Basal FBF and resistance were similar in the two groups. Hypercholesterolemia impaired the peak FBF response to ACh (11.1 +/- 1.9 vs. 17.6 +/- 2.2 ml/100 ml/min, P = 0.03), and reduced the peak response to sodium nitroprusside (6.0 +/- 0.4 vs. 8.1 +/- 0.6 ml/100 ml/min, P < 0.01). However, hypercholesterolemia did not affect peak hyperemic FBF (13.1 +/- 1.0 vs. 13.2 +/- 1.0 ml/100 ml/min, P = 1.0) or the FBF volume repayment during the 1 or 5 min after exercise. Resting FBF was reduced by L-NMMA to a similar degree (by 33% vs. 40%, P = 0.17) in both groups. Although L-NMMA reduced peak hyperemic FBF (by 16% vs. 17%, P = 0.93) and the volume repaid after exercise in both groups, there were no differences between the two groups. CONCLUSIONS: Exercise-induced metabolic vasodilation is in part dependent on NO release. Hypercholesterolemia impairs NO-mediated vasodilation, but is not associated with a reduction in exercise-induced hyperemia. This may indicate that multiple compensatory mechanisms are operative in skeletal muscle metabolic vasodilation.

Acetylcholine↗
PubMed1999

Relative contribution of vasodilator prostanoids and NO to metabolic vasodilation in the human forearm.

Although many factors are thought to contribute to the regulation of metabolic vasodilation in skeletal muscle vasculature, recent interest has focused on the role of the endothelium. We examined the relative roles of nitric oxide (NO) and of vasodilator prostanoids in the control of metabolically induced functional hyperemia in the forearm of humans. In 43 healthy volunteers [24 +/- 5 (SD) yr] we assessed resting and functional hyperemic blood flow (FHBF) in response to 2 min of isotonic forearm exercise before and after inhibition of NO and/or vasodilator prostanoid production with intra-arterial NG-monomethyl-L-arginine (L-NMMA, 2 mg/min) and aspirin (ASA, 3 mg/min), respectively. Blood flow was measured using venous occlusion plethysmography. L-NMMA and ASA decreased resting forearm blood flow by 42% (P < 0.0001) and 23% (P < 0.0001), respectively, whereas infusion of ASA followed by L-NMMA reduced flow by a further 24% (P < 0.05). L-NMMA reduced peak FHBF by 18% [from 13.9 +/- 1.0 to 11.4 +/- 1.1 (SE) ml. 100 ml forearm-1. min-1, P = 0.003] and the volume "repaid" after 1 and 5 min by 25% (8.9 +/- 0.7 vs. 6.7 +/- 0.7 ml/100 ml, P < 0.0001) and 37% (26.6 +/- 1.8 vs. 16.8 +/- 1.6 ml/100 ml, P < 0.0001). ASA similarly reduced peak FHBF by 19% (from 14.5 +/- 1.1 to 11.8 +/- 0.9. 100 ml forearm-1. min-1, P < 0.001) and the volume repaid after 1 and 5 min by 14% (7.5 +/- 0. 6 vs. 6.4 +/- 0.6 ml/100 ml, P = 0.0001) and 20% (21.2 +/- 1.5 vs. 16.9 +/- 1.5 ml/100 ml, P < 0.0001), respectively. The coinfusion of ASA and L-NMMA did not decrease FHBF to a greater extent than either agent alone. These data suggest that endothelium-derived NO and vasodilator prostanoids contribute to resting blood flow and metabolic vasodilation in skeletal muscle vasculature in healthy humans. Although these vasodilator mechanisms operate in parallel in exercise-induced hyperemia, they appear not to be additive. Other mechanisms must also be operative in metabolic vasodilation.

Adult↗
PubMed1999

Systemic arterial compliance is reduced in young patients with IDDM.

Arterial elastic properties are altered with increasing age and in various disease states, including non-insulin-dependent diabetes mellitus (NIDDM). Whether young patients with insulin-dependent diabetes mellitus (IDDM) have reduced arterial compliance before developing endothelial dysfunction or overt micro- and macrovascular disease is unclear. Systemic arterial compliance and endothelium-dependent, flow-mediated vasodilation (FMD) was assessed in 25 individuals with uncomplicated IDDM (23 +/- 4 yr, 14 females and 11 males) and compared with 30 age-matched controls (15 females and 15 males). Arterial compliance was determined via simultaneous measurements of aortic blood flow and carotid arterial pressure. The relationship between arterial compliance and endothelial function (assessed by brachial artery FMD) was also examined. Arterial compliance was 29% lower in IDDM subjects compared with control subjects (0.46 +/- 0.05 vs. 0.65 +/- 0.07 arbitrary compliance units, P < 0.05). Blood pressure, lipid levels, and daily energy expenditure (a measure of physical activity levels) were not different between groups. Compliance in the IDDM group was not related to the integrity of endothelial vasodilator function, disease duration, or degree of glycemic control. Arterial compliance is reduced in young patients with IDDM before the development of overt micro- or macrovascular disease. Early assessment of arterial compliance may be useful in predicting the development of diabetic vascular complications.

Adult↗
PubMed1999

Estrogen improves acetylcholine-induced but not metabolic vasodilation in biological males.

We have previously shown that chronic estrogen therapy improves endothelium-dependent vasodilation in the resistance vessels of biological males. Whether this is nitric oxide (NO) mediated and whether estrogen improves metabolic vasodilation is unknown. Resting forearm blood flow (FBF), ACh-induced vasodilation, and functional hyperemic blood flow (exercise) were assessed before and after the inhibition of NO with N(G)-monomethyl-L-arginine (L-NMMA) in 15 male-to-female transsexuals prescribed estrogen and in 14 age-matched males. Resting FBF was similar in the two groups and was similarly (P = 0.44) but significantly reduced by 48% after infusion of L-NMMA (P < 0.0001). The ACh dose-response relationship was shifted upward and to the left in the transsexual compared with the male group (P < 0.01). After the inhibition of NO, however, the difference in the ACh dose-response curve between the two groups was abolished (P = 0.15). Peak functional hyperemic blood flow was similar for the two groups (P = 0.94). L-NMMA produced a significant (P < 0.01) but similar (P = 0.64) reduction in peak hyperemia in the two groups. The volume of blood repaid to the forearm 1 and 5 min after exercise was also reduced by L-NMMA (P < 0.0001); however, there were no differences between the two groups. This suggests that ACh-mediated NO-dependent vasodilation may be more sensitive to the effects of chronic estrogen than exercise-induced vasodilation. Long-term estrogen does not appear to improve exercise-induced metabolic vasodilation in biological males, despite the fact that NO contributes to this process.

Acetylcholine↗
PubMed1999

Acute administration of 17beta-oestradiol does not improve endothelium-dependent vasodilatation in young men.

Studies have recently demonstrated that long-term oestrogen therapy improves endothelium-dependent and endothelium-independent vasodilatation in the conductance vessels of biological males. We sought to determine if an acute single dose of oestrogen might similarly improve vasodilator function in young males. In a randomized, double-blind, placebo-controlled, crossover study, we compared the effects of 1 mg of sublingual 17beta-oestradiol (E(2)) and placebo on endothelium-dependent and endothelium-independent vasodilatation in the brachial artery using a non-invasive ultrasound technique. We recruited 30 young males based on a power calculation. Neither acute sublingual oestrogen nor placebo affected flow-mediated vasodilatation [5.32+/-0.78% and 5.28+/-0.60% respectively (mean+/-S.E.M.), P=0.94]. Responses to nitroglycerine were similar after oestrogen or placebo (16.01+/-0.86% and 15.29+/-1. 19%, P=0.47). Basal blood flow and flow during reactive hyperaemia did not differ after oestrogen or placebo. Heart rate and blood pressure were similar during both treatment phases of the study. The absolute change in serum oestradiol levels was greater after the oestrogen treatment phase than after placebo (1509+/-87 versus -13+/-4 pmol/l, P<0.0001). Despite achieving supra-physiological oestradiol levels, the acute administration of sublingual E(2) does not appear to improve endothelium-dependent or endothelium-independent vasodilatation, at least acutely, in the brachial artery of young males. In keeping with our previous study, these data suggest that a period of oestrogen 'priming' (possibly to induce receptor-mediated nitric oxide synthesis) may be required to yield an improvement in vascular function in males.

Adult↗
PubMed1998

Bifuration coronary angioplasty using a new side branch accessible stent.

Two cases of successful angioplasty of bifurcational left anterior descending and diagonal lesions treated with a new side branch accessible Jomed stent in the LAD are discussed. A balloon dilatation of the side branch using kissing balloon technique in the first case and stenting the side branch followed by kissing balloon dilatation in the second case are described.

Angioplasty, Balloon, Coronary↗
PubMed1998

Continuous release of vasodilator prostanoids contributes to regulation of resting forearm blood flow in humans.

Continuous release of nitric oxide contributes to the maintenance of resting tone in the human forearm and coronary circulations; however, evidence for a similar role of vasodilator prostanoids such as prostacyclin is lacking. We examined whether continuous release of prostacyclin contributes to basal forearm blood flow. Flow was measured using venous occlusion plethysmography in 38 healthy volunteers [mean age 21.3 +/- 2.5 yr (+/- SD); 13 female, 25 male] at rest, after administration of three incremental intra-arterial infusions of either the cyclooxygenase inhibitor aspirin or placebo, and before and after administration of the endothelium-dependent and -independent dilators acetylcholine (30 micrograms/min) and nitroprusside (1 microgram/min). To assess the effect of aspirin on the production of prostacyclin, plasma 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha; the stable metabolite of prostacyclin) was measured by simultaneous arterial and venous sampling. Aspirin produced a time- and dose-dependent reduction in forearm blood flow, resulting in a 32% decrease at the highest dose. The effect was maximal after 10 min. Flow at rest and after aspirin doses of 1, 3, and 10 mg/min was 2.6 +/- 0.2, 2.3 +/- 0.2, 2.1 +/- 0.2, and 1.8 +/- 0.2 ml.100 ml forearm tissue-1.min-1, respectively (means +/- SE, P < 0.001). Commensurate with these data, the net forearm production of 6-keto-PGF1 alpha was 52.9 +/- 16.4, 11.7 +/- 8.6, 18.7 +/- 8.5, and 12.0 +/- 12.5 pg.100 ml forearm tissue-1.min-1 for the respective doses (P = 0.04). No time-dependent reduction in flow was seen in subjects with vehicle infusion. Aspirin did not affect the responses to acetylcholine or nitroprusside. These data suggest that continuous release of prostacyclin plays a role in the maintenance of resting forearm blood flow. There appears to be a direct link between the reduction in flow with aspirin and inhibition of prostacyclin production.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Long-term estrogen therapy improves vascular function in male to female transsexuals.

OBJECTIVES: This study sought to examine the effects of long-term estrogen therapy on vascular function in male to female transsexuals and to compare the findings with those observed in men and premenopausal women. BACKGROUND: Gender differences in coronary artery disease have largely been attributed to the beneficial effects of estrogen on vascular function and plasma lipids in women. However, the effects of estrogen on the male vasculature have not been widely studied. METHODS: We compared the effects of estrogen on vascular function in 14 male to female transsexuals, 14 age-matched men and 15 premenopausal women. Flow-mediated vasodilation and response to nitroglycerin were assessed in the brachial artery using noninvasive ultrasound. RESULTS: Flow-mediated vasodilation was similar in transsexuals and women but greater than that in men ([mean +/- SE] 11.5 +/- 1.3% and 9.4 +/- 1.1% vs. 5.2 +/- 1.0% respectively, p < 0.005). Responses to nitroglycerin were also greater in transsexuals and women than in men (21.6 +/- 1.7% and 21.0 +/- 0.9% vs. 14.5 +/- 1.2%, respectively, p = 0.0005). These differences persisted even after adjusting for vessel size. Despite similar total cholesterol levels, transsexuals had high density lipoprotein cholesterol levels similar to those in women and greater than those observed in men (1.76 +/- 0.12 and 1.82 +/- 0.11 mmol/liter vs. 1.35 +/- 0.07 mmol/liter, respectively, p < 0.005). Moreover, triglyceride levels were greater in transsexuals than in men and women, and low density lipoprotein cholesterol (LDL-C) particle size was smaller (25.7 +/- 0.2 nm vs. 26.2 +/- 0.1 and 26.6 +/- 0.1 nm, respectively, p = 0.0001). Serum testosterone (an index of estrogen therapy in transsexuals) was markedly suppressed in transsexuals and similar to that in women. Univariate analysis revealed that there was a strong inverse correlation between serum testosterone and flow-mediated vasodilation (r(s) = -0.48, p < 0.005). Multivariate analysis revealed that the best combination of predictors of flow-mediated vasodilation was serum testosterone, vessel size and LDL-C (R2 = 0.3, p < 0.005). CONCLUSIONS: Long-term estrogen therapy appears to improve vascular function in male to female transsexuals and occurs despite higher triglyceride levels and the presence of small, dense LDL-C. The beneficial effects of estrogen are not gender specific or solely mediated through endothelium-derived nitric oxide.

Adult↗