Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli.

OBJECTIVE: To examine the relation between endothelial dependent and endothelial independent stimuli of varying intensity and measures of vascular function in the brachial artery of young healthy adults, to determine whether these responses are consistent and can be used to assess endothelial function. DESIGN AND SETTING: High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperaemia induced by forearm cuff occlusion, and after sublingual isosorbide dinitrate (ISDN). Each subject was assigned to a random order of six cuff occlusion times (30 seconds, 1.5, 2.5, 3.5, 4.5, and 8 minutes) and six doses of ISDN (10, 20, 50, 100, 200, and 400 micrograms). SUBJECTS: Three males and three females mean age 31 years (range 25 to 43) with no known risk factors for cardiovascular disease. MAIN OUTCOME MEASURES: Flow mediated, endothelial dependent dilatation was compared to duration of cuff occlusion, peak reactive hyperaemia, and duration of increased flow. Nitrate induced, endothelial independent dilatation was compared to dose of ISDN and change in flow. RESULTS: Vessel dilatation and duration of peak flow change increased with longer duration of cuff occlusion. After 4.5 minutes of occlusion, flow mediated dilatation was mean (SD) 96 (6)% of maximal response and did not increase significantly with longer occlusion times. No significant dilatation occurred after 10 or 20 micrograms of ISDN in any subject. With increasing doses up to 200 micrograms there was an increase in dilatation. Endothelial independent dilatation did not increase significantly with doses of ISDN above 200 micrograms. CONCLUSIONS: Measures of arterial function vary with duration of blood flow occlusion and ISDN dose. Maximum arterial response was reached in all subjects after 4.5 minutes of blood flow occlusion or 200 micrograms of ISDN. Therefore, these variables produce consistent reproducible measures of endothelial function.     

Does a glass of red wine improve endothelial function?

AIMS: To examine the acute effect of red wine and de-alcoholized red wine on endothelial function. METHODS AND RESULTS: High frequency ultrasound was used to measure blood flow and percentage brachial artery dilatation after reactive hyperaemia induced by forearm cuff occlusion in 12 healthy subjects, less than 40 years of age, without known cardiovascular risk factors. The subjects drank 250 ml of red wine with or without alcohol over 10 min according to a randomized procedure. Brachial artery dilatation was measured again 30 and 60 min after the subjects had finished drinking. The subjects were studied a second time within a week of the first study in a cross-over design. After the red wine with alcohol the resting brachial artery diameter, resting blood flow, heart rate and plasma-ethanol increased significantly. After the de-alcoholized red wine these parameters were unchanged. Flow-mediated dilatation of the brachial artery was significantly higher (P<0.05) after drinking de-alcoholized red wine (5.6+/-3.2%) than after drinking red wine with alcohol (3.6+/-2.2%) and before drinking (3.9+/-2.5%). CONCLUSION: After ingestion of red wine with alcohol the brachial artery dilated and the blood flow increased. These changes were not observed following the de-alcoholized red wine and were thus attributable to ethanol. These haemodynamic changes may have concealed an effect on flow-mediated brachial artery dilatation which did not increase after drinking red wine with alcohol. Flow-mediated dilatation of the brachial artery increased significantly after de-alcoholized red wine and this finding may support the hypothesis that antioxidant qualities of red wine, rather than ethanol in itself, may protect against cardiovascular disease.     

Reduction of peripheral flow reserve impairs endothelial function in conduit arteries of patients with essential hypertension

BACKGROUND: A diminished flow reserve in resistance vessels is a hallmark of hypertensive microvascular disease. Hypertension is associated with structural alterations in the microcirculation and a reduced endothelium-dependent dilation in conduit arteries. Both have been demonstrated to predict future cardiovascular events. OBJECTIVE: We hypothesized that a reduced peripheral flow reserve impairs endothelial function in upstream conduit arteries in patients with arterial hypertension. DESIGN: In 43 hypertensive patients (HT) and 38 normotensive controls (NT) endothelial function of the brachial artery was assessed by measurement of flow-mediated dilatation (FMD), using high-resolution ultrasound. Peripheral flow reserve (FR) was determined via measurements of forearm blood flow at rest and during increments of reactive hyperaemia, using venous occlusion plethysmography. RESULTS: FMD was markedly impaired in HT (3.6 +/- 0.3%) as compared with NT (10.2 +/- 0.3%), whereas maximum brachial artery diameter following endothelium-independent dilatation was similar in both groups. In hypertensive patients FR was significantly reduced (HT, 3.2 versus NT, 6.0) during reactive hyperaemia after 5 min of ischaemia. FR was associated with FMD (r = 0.68, P < 0.01). Multiple stepwise regression analysis identified FR as a strong independent variable determining the extent of FMD (r2 = 0.46, P < 0.01). In HT the dose-response curve of FMD upon stepwise increases of FR was shifted significantly to the right. Normalization of FR improved FMD in HT by more than 60%. CONCLUSIONS: In essential hypertension a reduced FR contributes to the endothelial dysfunction of upstream conduit arteries. These findings may have therapeutic and prognostic implications in patients with arterial hypertension.     

Flow-mediated vasodilation of the femoral and brachial artery induced by exercise in healthy nonsmoking and smoking men.

OBJECTIVES: We sought to analyze diameter changes of conduit arteries in response to whole-body exercise and hypothesized that this response might be endothelium-dependent and, therefore, impaired in smokers. BACKGROUND: Hyperemia and coincident vasodilation are pivotal mechanisms for meeting the increased metabolic demands of active muscle tissue during physical exercise, but studies in humans are sparse. METHODS: We studied diameter and blood flow of the femoral and brachial arteries in response to a submaximal bicycle exercise test in 10 nonsmoking and 8 smoking healthy male subjects. During an exercise period of 40 min the investigated conduit arteries were periodically scanned in longitudinal sections by high-resolution ultrasound. In the same subjects flow-mediated dilation (FMD) of the brachial artery was recorded by inducing an ischemia through a forearm-occluding cuff. RESULTS: In response to exercise the diameter of the femoral artery significantly increased in both nonsmokers and smokers, with a diminished response in smokers (9.2 +/- 1.9% vs. 4.8 +/- 1.6%, p < 0.001). Flow-mediated dilation of the brachial artery induced by forearm occlusion was also reduced in smoking subjects, revealing a strong correlation between these different methods of FMD (exercise vs. forearm ischemia) (r = 0.88, p < 0.001). In contrast, blood flow increase of the femoral artery was similar in nonsmoking and smoking subjects (392 +/- 77% vs. 382 +/- 109%, p = NS). CONCLUSIONS: Conduit arteries react with a flow-mediated dilation in response to whole-body exercise. The impairment of this vasodilation observed in smokers was strongly related to a decrease of endothelium-dependent dilation induced by forearm ischemia, indicating that endothelial dysfunction represents the underlying mechanism.     

The effects of mental stress and the cold pressure test on flow-mediated vasodilation

As a stressful lifestyle has been associated with coronary heart disease, this study aim to evaluate how two stressful tests influence endothelial-dependent vasodilation evaluated by flow-mediated dilation (FMD) of the brachial artery. FMD following 5 min of occlusion of the forearm was evaluated in young healthy volunteers with measurements of brachial artery diameter and blood flow (BABF) using ultrasound before and during a mental arithmetic task (MAT), and during cold pressure test (COP). MAT and COP increased blood pressure to a similar degree (18-21 mmHg). The COP induced a significant reduction in FMD compared to the baseline levels (from 9.3 +/- 3.9 to 5.9 +/- 3.2%, p < 0.01), as well as to the MAT, which in itself did not influence FMD (10.1 +/- 5.0%). However, as MAT increased BABF during hyperaemia significantly, the FMD to BABF ratio was significantly reduced by both stress tests (p < 0.05). Time-control experiments showed FMD measurements to be reproducible and that MAT and COP by themselves only marginally affected brachial artery diameter. In conclusion, cold pressure stress induced an impairment in FMD, but no effect was induced by a MAT. However, when FMD was normalized for the degree of hyperaemic blood flow, the driver of the vasodilation in the brachial artery, a reduction in flow-mediated vasodilation was seen during both mental and cold pressure stress.     

The effect of acute hyperglycaemia on brachial artery flow mediated dilatation in normal volunteers

Abstract Background : Endothelial function is known to be abnormal in patients with diabetes and acute hyperglycaemia may play an aetiological role.
Aims : The aim of this randomised controlled study was to determine if acute systemic hyperglycaemia impairs endothelial function in normal subjects.
Methods : Endothelial function was assessed by the change in brachial artery diameter in response to forearm ischaemia using B-mode ultrasound in ten healthy subjects (eight male) aged 19–35 years. Brachial artery blood flow velocity and diameter were measured before and after five minutes of forearm ischaemia. Measurements were performed in the supine position after an overnight fast, before and after 60 minute infusions of 0.9% saline or 10% dextrose. Measurements were made on two separate occasions at least 24 hours apart, and subjects were randomised to saline first or dextrose first. The largest diameter measured after ischaemia was divided by the resting arterial diameter to calculate percent dilatation of the artery from baseline, and is reported as flow-mediated dilatation (FMD).
Results : Dextrose infusion resulted in a significant rise in mean (SD) serum glucose 5.2 (0.1) to 9.2 (0.3) mmol/L and insulin concentration 6.3 (1.4) to 20.6 (3.7) mU/L p <0.002. Brachial artery blood flow velocity and diameter increased significantly from baseline after ischaemia ( p <0.002). Mean FMD (SEM) before and after infusion were not, however, significantly different ( p =0.4) (pre-saline 7.3 [1.0]%, post saline 5.2 [1.5]% and predextrose 8.1 [2.0]%, post dextrose 5.9 [1.7]%).
Conclusions : These data suggest that acute hyperglycaemia does not impair FMD in normal subjects.     

Endothelium-dependent flow-mediated vasodilatation,insulin resistance and the metabolic syndrome in 60-year-old men

OBJECTIVES: To evaluate the endothelium-dependent flow-mediated vasodilatation (FMD) in the brachial artery and to study the relationship to insulin sensitivity and to the metabolic syndrome in 60-year-old clinically healthy men. SUBJECTS: The men were randomly selected from the general population (n = 55). The subjects with the metabolic syndrome were defined according to a definition proposed by a working group associated with the World Health Organization (WHO). METHODS: Ultrasound images for measurement of lumen diameter of the brachial artery were recorded before and after reactive hyperaemia induced by occlusion of the artery, both with and without ischaemic hand exercise during the occlusion. Insulin-mediated glucose uptake was determined by euglycaemic hyperinsulinaemic clamp as a measure of insulin sensitivity. RESULTS: The FMD was in the total group 3.2% when hyperaemia was induced by occlusion only and 8.7% after occlusion plus ischaemic hand exercise (P < 0.001, n = 51). However, no relationship was observed between any measure of FMD and insulin-mediated glucose uptake (r = -0.05 and r = 0.06, n = 47, P > 0.30). Furthermore, subjects with the metabolic syndrome (n = 13) did not differ in any measure of FMD compared with those with no risk factors (n = 11). CONCLUSION: In this study the ultrasound method to evaluate endothelial function did not show that low insulin sensitivity or the metabolic syndrome were associated with impaired FMD in otherwise clinically healthy 60-year-old men.     

Characteristics of flow-mediated brachial artery vasodilation in human subjects

In an effort to determine whether arterial conductance vessels dilate in response to increased blood flow stimuli, brachial artery area (cm2) and diameter (cm) were derived by simultaneous measurement of forearm blood flow (ml/min.100 ml) and brachial artery blood flow velocity (cm/sec) following the release of arterial occlusion. Measurements were made at rest and at the time of maximal flow after the release of graded periods of forearm arterial occlusion (20 seconds to 10 minutes). These studies showed a graded large vessel dilation following occlusions of up to 1 minute (baseline diameter, 0.33 +/- 0.01; after 1 minute occlusion, 0.45 +/- 0.02 cm; p less than 0.05) after which time diameter plateaued (after 10 minutes of occlusion, 0.48 +/- 0.02 cm). In addition, the time course of diameter and flow changes after 3 minutes of arterial occlusion were examined. Flow was maximal at 5 seconds but diameter was maximal at 15-30 seconds after release. Furthermore, the half time for the return of diameter to baseline was longer than that for blood flow. We also measured the diameter after forearm heating (42 degrees C) and noted a substantial increase in diameter (before heating, 0.32 +/- 0.01; after heating, 0.39 +/- 0.02 cm; p less than 0.05). Finally, we applied pressure to the venous side of arteriovenous fistulae in five hemodialysis patients. This maneuver was associated with large reductions in forearm blood flow (baseline flow, 63.3 +/- 10.6; venous compression flow, 36.0 +/- 4.4 ml/min.100 ml; p less than 0.05) and a decrease in brachial artery size (baseline diameter, 0.63 +/- 0.07; venous compression diameter, 0.58 +/- 0.06 cm; p less than 0.05). We conclude that 1) the human brachial artery size changes in response to changes in blood flow, and 2) the maximal dilation occurs after maximal flow is noted. Although alternate explanations are possible for each of our observations, our results are most consistent with a flow-mediated, localized vasodilating process.     

Peripheral hemodynamic and biological effects of perindopril in the healthy subject. Dose-effect relationship

The effects of three doses of perindopril (4.8 and 16 mg), a new angiotensin I-converting enzyme inhibitor, and of a placebo on systemic blood pressure, heart rate, brachial artery flow and diameter, forearm vascular resistance and the renin angiotensin system biological parameters (plasma converting enzyme activity PCEA, renin activity PRA and aldosterone PA) were compared during a double-blind cross-over study performed in six healthy volunteers. Perindopril dose-dependently inhibited PCEA, increased PRA, augmented brachial artery flow and diameter and decreased forearm vascular resistance, whereas it did not affect systemic blood pressure and heart rate. The perindopril-induced increase in brachial artery flow was related (a) at the low dose to the sole arteriolar and (b) at the two highest doses to both arteriolar and large vessels dilatation. Finally, during the ten first hours following drug intake, there was a significant correlation between perindopril-induced PCEA inhibition and brachial artery flow increase.     

Reproducibility of brachial ultrasonography and flow-mediated dilatation (FMD) for assessing endothelial function

Abstract Background : High-resolution brachial artery ultrasonography is used to study vasodilator response induced by physiologic reactive hyperaemia. We examined the reproducibility of measuring flow-mediated dilatation (FMD) on two occasions.
Aims : To determine the degree of variability of this technique in our vascular laboratory for the design of clinical research studies.
Methods : Nineteen subjects were studied on two separate occasions using an Acuson 128 ultrasound device and a 7.0 MHz linear array transducer. Reactive hyperaemia was induced in the brachial artery by inflation and release of a blood pressure cuff. Nitrate-induced dilatation was assessed in 11 of the 19 subjects. Measurements were made by two observers blinded to subject details.
Results : The 11 subjects given sublingual GTN during the first ultrasound study had a mean nitrate-induced dilatation of 20.7% (sd 9.6). The mean vessel diameter of 3.78 mm (sd 0.7) at rest and 3.89 mm (sd 0.7) during reactive hyperaemia yielded a mean FMD of only 3.0% (sd 2.7). The mean difference in FMD within-observers was 0.13% (sd 2.07), between-observers 0.06% (sd 2.17) and between-studies was 0.57% (sd 6.83).
Conclusions : The reproducibility of FMD measured by brachial artery ultrasound was poor and likely to render the measurements inaccurate for clinical research in our hands. Between-study variation contributed the largest proportion of total study variability. We suggest that investigators using this technique conduct their own careful reproducibility studies in order to avoid the misinterpretation of 'negative' studies.     

Endothelial dysfunction in cardiologists after 24 hours on call

The objective was to determine if the stress caused by 24 hours on call in a cardiology emergency room alters endothelial function assessed by high-resolution ultrasonography in the brachial artery.Fifteen young physicians were studied in a crossover design: a) after a normal night of sleep at home, and b) after 24 hours on call without sleeping in an emergency room. Both studies were made at rest, 5 minutes after forearm occlusion and 3 minutes after administration of sublingual nitroglycerin. High-resolution ultrasonography and a 7.5-MHz linear array transducer were used to measure the brachial artery lumen.After 24 hours on call, physicians had significantly higher resting systolic and diastolic blood pressure. They also had a non-significant increase in heart rate and a lower brachial artery diameter. Brachial artery dilatation caused by hyperemia was only 3.35%, while it increased to 11.34% after normal sleep (p < 0.001). Only 2 physicians showed more than 4.4% dilatation, which was considered a normal response, while 13 had more than 4.4% after a normal night of sleep at home (p < 0.01). The response to nitroglycerin was similar under control conditions and after 24 hours of duty oncall.In conclusion, stress caused by 24 hours on call in a cardiology emergency room depresses or abolishes endothelial function.     

Habitual resistance exercise and endothelial ischemia-reperfusion injury in young adults

Resistance exercise involves muscular contractions that can render downstream tissues ischemic and may precondition the vasculature against ischemia-reperfusion (IR) injury, but it is unknown if habitual resistance exercise protects against IR injury in humans. We determined the magnitude and recovery from endothelial IR injury induced by forearm occlusion in 22 healthy young sedentary and resistance-trained adults. After IR injury, brachial artery flow-mediated dilation (FMD) significantly decreased by 36% in sedentary, but not resistance-trained subjects and fully recovered within 45 min. Though HDL-cholesterol, handgrip strength and systolic blood pressure were significantly associated with FMD 15 min after IR injury, the change in FMD from before to 15 min after IR injury was not associated with any subject characteristics. These results are consistent with the notion that habitual resistance exercise may protect against endothelial IR injury in young adults, presumably through effects analogous to ischemic preconditioning.     

Impaired myocardial perfusion reserve but preserved peripheral endothelial function in patients with Fabry disease

Summary Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder due to deficient α-galactosidase A activity, which leads to accumulation of glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. The effect of this accumulation on peripheral and cardiac vascular function is poorly known. We studied 15 Fabry patients (mean age 35 years and mean BMI 24.8 kg/m2) and 30 age- and BMI-matched healthy controls to examine whether myocardial perfusion reserve and peripheral artery endothelial function are altered. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and H₂ ¹⁵O. Myocardial blood flow reserve was calculated as the ratio between the dipyridamole-induced maximal blood flow and resting blood flow. Peripheral artery endothelial function was assessed by measuring the brachial artery flow-mediated dilatation using ultrasound at rest and during reactive hyperaemia. The myocardial perfusion reserve was significantly lower in Fabry patients than in controls (3.3 ± 1.2 vs 4.4 ± 1.6, p = 0.02), while the brachial artery flow-mediated dilatation was similar (5.9% ± 3.9%vs 4.5% ± 3.6%, p = 0.27). Thus, inFabry disease, myocardial perfusion reserve is reduced while the peripheral artery endothelial function is preserved.     

Large and small artery endothelial function in patients with essential hypertension--effect of ACE inhibition and beta-blockade

Hypertension has been associated with changes in endothelial function in both large muscular arteries and small resistance arteries. We evaluated the relationship between blood flow velocity and dilatation of the brachial artery following transient forearm ischemia and acetylcholine-induced relaxation in subcutaneous small arteries and the influence of antihypertensive therapy on both in patients with essential hypertension. Thirty-one previously untreated hypertensive patients were randomized in a double-blind fashion to treatment with either the angiotensin-converting enzyme (ACE) inhibitor perindopril or the beta-blocker atenolol and compared with 17 healthy normotensive controls. Before and after 1 year of treatment, while still on active medication, flow-mediated dilatation (FMD) was measured in the brachial artery using ultrasound while relaxation to acetylcholine in small arteries was tested in vitro in a myograph. FMD correlated inversely to resting brachial artery diameter (r = -0.38, p<0.05). FMD corrected for resting diameter (FMD(corr)) was lower in patients (3.0+/-0.2%) compared with controls (4.2+/-0.3%, p<0.01). In both patients and controls, FMD(corr) was related to flow velocity in a non-linear way with FMD(corr) reaching a maximum despite increasing flow velocities, and in the patients, FMD(corr) was only reduced at high flow velocities. Furthermore, patients had a reduced acetylcholine-induced relaxation in small arteries (p = 0.04). Perindopril and atenolol reduced blood pressure to similar levels and both drugs improved FMD(corr) to a similar degree without any effects on relaxation to acetylcholine in small arteries. The present study demonstrates the role of correcting for differences in baseline diameter during measurements of FMD and a non-linear relationship between flow velocity and FMD in the brachial artery. Furthermore, the results suggest different effects of antihypertensive treatment on endothelial function in large and small arteries.     

Evaluation of the Determinants of Flow — Mediated Radial Artery Vasodilatation in Humans

The relative importance of the early peak response during hyperaemia and of the duration of the hyperaemic phase (tl/2: blood flow velocity half time and AUCt1/2: area under the curve of flow velocity at tl/2) in the magnitude of the flow-dependent vasodilatation of the radial artery was determined in humans. Radial artery diameter was measured continuously in 18 healthy volunteers using an echotracking system coupled to a Doppler device for the measurement of the radial blood flow. In 9 subjects, arterial parameters were measured at baseline and during 3 hyperaemic tests performed after 2, 5 or 10 minutes of ischaemia. Reproducibility of the measured parameters was studied in 9 other subjects. Radial artery diameter, AUCt1/2 and t1/2 increased proportionally with the duration of ischaemia. In contrast, the peak flow response was already maximal after 5 minutes of ischaemia. The regression analysis showed that the best fit model after stepwise analysis only included t1/2 (r=0.85, p<0.001). There was no correlation between the peak flow values andthe duration of hyperaemia (14.29, pd.14). These results demonstrate that conduit arteries postischaemic flow-dependent vasodilatation in humans is both determined by the peak value and by the duration of the hyperaemic phase and suggest that these two components must be consirered when comparing this index of NO release between different groups of subjects.     

Antiplasmin correlates to arterial reactivity in a healthy population of 35-year-old men and women

OBJECTIVE: To study whether haemostasis function variables correlate with endothelial function and other vasomotion characteristics of the brachial artery in a randomly selected healthy population of 35-year-old men and women. DESIGN: Endothelial function was measured as flow mediated dilatation (FMD) of the brachial artery during reactive hyperaemia and the nonendothelial dependent dilatation after sublingual nitroglycerin (NTG) was administered. Haemostasis and fibrinolysis function were estimated by analysis of von Willebrand factor, plasminogen activator inhibitor-1, antiplasmin and fibrinogen. SETTING: A general medicine research centre and a university hospital. SUBJECTS: Randomly chosen men (n = 53) and women (n = 56). RESULTS: Univariate correlation analysis showed significant correlations between haemostasis factors, conventional risk factors for cardiovascular disease and indices of vasomotion of the brachial artery. In multivariate analysis, with haemostasis variables and conventional risk factors included, antiplasmin was the strongest explanatory variable for FMD. When antiplasmin was removed from the analysis, the r-value dropped from 0.46 to 0.35. Antiplasmin also correlated with NTG-induced dilatation (positively) and brachial diameter at rest (negatively), albeit less consistently. CONCLUSIONS: Antiplasmin correlates significantly and independently to FMD, reflecting endothelial function, and also to brachial artery diameter at rest and nitroglycerin-induced dilatation. In multivariate analysis these correlations of antiplasmin to arterial characteristics were stronger than for 'conventional' risk factors, such as smoking, blood pressure and serum cholesterol.     

Augmented hyperaemia and reduced tissue injury in response to ischaemia in subjects with the 34C > T variant of the AMPD1 gene.

AIMS: In patients with coronary artery disease, the 34C > T variant of the adenosine mono-phosphate deaminase gene (AMPD1), encoding a dysfunctional protein, predicts improved survival. We hypothesized that in subjects with this variant allele, ischaemia-induced intracellular adenosine formation is increased, augmenting reactive hyperaemia and ischaemic tolerance. METHODS AND RESULTS: We selected 10 healthy subjects with the CT genotype and 10 CC controls. The forearm vasodilator response to 2 and 5 min of ischaemia (venous occlusion plethysmography, expressed as percentage of maximum blood flow after 13 min of ischaemia) was higher in the CT group 56% (49-74%) and 77% (71-86%) vs. 49% (42-53%) and 60% (55-70%) in the CC group [median (interquartile range), P = 0.01]. Additionally, ischaemia-reperfusion injury was assessed in the thenar muscle using (99m)Tc-annexin A5 scintigraphy after forearm ischaemic exercise to detect externalized membrane phosphatidylserines. At reperfusion, (99m)Tc-annexin was administered intravenously. The change in annexin targeting between 1 and 4 h post-injection was -2.3% (interquartile range -2.4 to -1.6%) in the CT group vs. -0.3% (-0.6 to 1.3%) in controls (n = 7 in both groups, P = 0.03). CONCLUSION: The 34C > T variant of AMPD1 augments vasodilation and reduces tissue injury in response to forearm ischaemia. These mechanisms could contribute to the survival benefit of cardiovascular patients with this variant allele.     

Myocardial contrast echocardiography: influence of ischaemia and hyperaemia in an animal model.

To evaluate changes in myocardial contrast echocardiography during ischaemia and hyperaemia, contrast studies were performed in 16 open chest dogs. Time-intensity curves were generated using videodensitometry after contrast injections to demonstrate ischaemic and non-ischaemic areas of interest during a wide range of coronary blood flow levels. For each time-intensity curve, the peak contrast intensity (PCI), washout halftime (T1/2) and area under the curve (AUC) were calculated. PCI and AUC decreased significantly only with severe ischaemia (90% or more reduction in flow), and increased significantly with hyperaemia of more than 2.5 times baseline flow. Both ischaemia and hyperaemia were found to prolong the T1/2. There was only a moderate linear correlation between the magnitude of hyperaemia and myocardial contrast echocardiographic parameters. There was significantly less increase in myocardial contrast echocardiographic parameters during hyperaemia in segments supplied by a stenosed coronary artery.     

Effects of nifedipine on coronary reactive and exercise induced hyperaemia

The effects of nifedipine on coronary vasodilation were studied during reactive hyperaemia after a transient coronary occlusion and during active hyperaemia associated with graded treadmill exercise. Studies were performed in 10 chronically instrumented dogs in which left circumflex coronary artery flow was measured with an electromagnetic flowmeter and myocardial oxygen extraction was determined from indwelling aortic and coronary sinus catheters. Thirty minutes after administration of nifedipine (10 micrograms.kg-1 iv), when coronary blood flow, arterial pressure, and heart rate had returned to control values, the vasodilatation following a 10 s coronary occlusion was significantly blunted, so that reactive hyperaemia blood flow debt repayment (mean(SEM)) was reduced from 387(39)% during control conditions to 270(33)% after nifedipine (p less than 0.05). In contrast, nifedipine did not alter the coronary vasodilatation that occurred in response to graded treadmill exercise so that the increase in coronary blood flow during exercise was not different from the control response. Thus, although nifedipine blunted ischaemic coronary vasodilatation during reactive hyperaemia, it did not alter coronary vasodilatation during active hyperaemia resulting from physiological increases of myocardial oxygen consumption.     

Role of endothelium-derived nitric oxide in sustained flow-dependent dilatation of human peripheral conduit arteries

Endothelial dysfunction is involved in the pathogenesis of cardiovascular diseases and is generally associated to the decrease in arterial nitric oxide (NO) availability. In humans, endothelial function can be evaluated by the post-ischaemic flow-dependent dilatation (FDD) of peripheral conduit arteries which is mainly mediated by the NO release when short duration of reactive hyperaemia are used (3 to 5 min ischaemia). However, recent studies suggest that the role of NO in this response decreases as the duration of the hyperaemic stimulation increases. The aim of the present study was thus, to evaluate, in healthy subjects, the role of NO in the FDD of conduct arteries in response to a sustained stimulation. Radial artery diameter (echotracking) and flow (Doppler) were measured, 7 cm under the elbow line, at baseline and during post-ischaemic hyperaemia (10 min wrist cuff inflation) in 10 healthy subjects (age: 24 +/- 1 years) in control period and after acute blockade of the endothelial NO-synthase by local infusion of NG-monomethyl L-arginine (L-NMMA, brachial artery, 8 mumol/min, 7 min). Endothelium-independent dilatation was studied by mean of sodium nitroprusside infusion (SNP: 5, 10 and 20 nmol/min, 3 min each dose before and after L-NMMA). L-NMMA administration decreased radial artery blood flow at base (Control: 14 +/- 2 vs L-NMMA: 10 +/- 1 ml/min, P < 0.05) and increased radial artery vasodilatation in response to SNP (P < 0.05) thus, demonstrating NO-synthase inhibition. Therefore, after L-NMMA there was a small decrease in radial FDD (Control: base: 2.52 +/- 0.05 mm, FDD: 11.3 +/- 0.6% vs L-NMMA: base: 2.51 +/- 0.04 mm: FDD: 9.0 +/- 0.9%; p < 0.05) without change in hyperaemia. In conclusion, our results demonstrate, in contrast to those obtained after short duration of hyperaemia, that the relative implication of NO in the flow-dependent vasodilatation of peripheral conduit arteries in humans decreases in response to sustained stimulation and suggest, in these experimental conditions, an associated flow-dependent vasodilating mechanism that is unaffected by the NO-synthase inhibition.