Effects of adenosine on cardiac performance and phosphate compounds in microembolised guinea pig hearts.

OBJECTIVE: The excessive release of adenosine has been reported to cause hyperaemia and to attenuate ischaemic injury in microembolised hearts. The direct effects of exogenous adenosine on cardiac performance were investigated in microembolised guinea pig hearts with the simultaneous measurement of phosphate compounds. METHODS: 21 male guinea pig hearts were perfused according to the Langendorff technique and microembolism was induced by injecting microspheres. Hearts were then treated as follows: group A, adenosine 20 microM and theophylline 60 microM; group B, theophylline 60 microM; group C, saline (control). Cardiac performance was monitored and phosphate compounds were measured by 31P magnetic resonance spectroscopy. RESULTS: Group A showed a significant increase in the left ventricular developed pressure and coronary flow, and a modest restoration of ATP content. Pi/(Pi+Pcr) remained virtually constant. There were no significant changes in left ventricular developed pressure or coronary flow in groups B and C. There was a gradual decrease in tissue ATP content and slight increase in Pi/(Pi+Pcr). CONCLUSIONS: Adenosine improved cardiac performance without adverse effect on energy metabolism in microembolised hearts. Adenosine also restored the ATP stores in microembolised hearts. (Pi = inorganic phosphate; Pcr = phosphocreatine.)     

Regulation of ischemic muscle metabolism in peripheral arterial occlusive disease

A review of metabolic pathways is presented, which are involved in muscular energy production during hypoxia according to recent experimental findings. By means of own exercise examinations the course of reactions providing ATP anaerobically in the muscles of limbs with poor circulation is analysed. Therefore, the arteriovenous differences in the concentrations of lactate, pyruvate, ammonia, hypoxanthine and alanine in the femoral blood of patients with stage II AOD were determined. In addition, the intracellular phosphorus compounds ATP, PCr and Pi as well as the tissue pH were measured noninvasively in the calf muscles using 31P magnetic resonance spectroscopy. The results give evidence for marked activation of the creatine kinase reaction, of glycolysis, of the myokinase reaction and of the purine nucleotide cycle in the ischaemic musculature at loads of short duration, which are in total sufficient to maintain the concentration of ATP even during claudication pain. In spite of salvage pathways like alanine formation, the end products of these "emergency reactions", Pi, H+ and NH4+, accumulate and exert deleterious cytotoxic effects, which are thought to be responsible for rapid muscle fatigue and claudication pain in PAOD.     

The effect of coronary perfusion with an oxygenated celsior solution on 12-hour cardiac preservation

Celsior is a new extracellular-type cardiac preservation solution. We recently developed an apparatus for preservation using low-pressure continuous coronary perfusion. The purpose of this study was to investigate the efficacy of coronary perfusion with an oxygenated Celsior solution using the new apparatus for prolonged cardiac preservation. Adult mongrel dogs weighing 9–13 kg were divided into two groups: the coronary perfusion group (CP; n=5) and the simple immersion group (SI; n=7). The coronary vascular beds were washed out with a 4°C Celsior solution following cardiac arrest using the same solution, and their hearts were excised. In the CP group, the graft was immersed in a 4°C Celsior solution and perfused with the same oxygenated solution. In the SI group, the graft was simply immersed in a 4°C Celsior solution. -adenosine triphosphate (-ATP), phosphocreatine (Pcr), inorganic phosphate (Pi) levels and myocardial pH (pHi) were measured immediately after excising the heart, and at 3, 6, and 12 hours after preservation. -ATP, Pcr, and Pi values were expressed as a percentage of control values, which were measured immediately after excising the heart. -ATP/Pi and Pcr/Pi levels were significantly higher in the CP group than in the SI group at 6 and at 12 hours after preservation. The pHi levels during preservation were significantly higher in the CP group than in the SI group. Low-pressure hypothermic coronary perfusion with an oxygenated Celsior solution is effective for long-term heart preservation.This paper was presented in part at the 41^st Annual World Congress of the International College of Angiology, Sapporo Japan, July 1999.     

Ischemic stroke in patients with intermittent claudication: a clinical study of 142 cases

The clinical features, risk factors, neuroimaging findings, and outcome of acute ischemic stroke were assessed in patients with intermittent claudication. Data from 142 patients with ischemic stroke and intermittent claudication were collected from a prospective hospital-based stroke registry in which 2500 consecutive acute stroke patients attended over a 12-year period. Ischemic stroke in patients with intermittent claudication accounted for 7.7% of all ischemic strokes (n = 1840). Ischemic stroke with and without intermittent claudication showed a similar in-hospital mortality rate (16% vs 14%) and absence of functional limitation at hospital discharge (20.5% vs 18.5%). Ischemic stroke patients with intermittent claudication showed a significantly shorter length of stay than patients without symptomatic peripheral arterial disease (14.6 vs 18.8 days, p < 0.05). Ischemic heart disease, transient ischemic attack (TIA), renal dysfunction, and watershed infarct were significant independent predictors of ischemic stroke in patients with intermittent claudication. Although cerebral infarction in patients with intermittent claudication showed a clinical profile suggestive of poor outcome, the prognosis was similar to that of ischemic stroke without intermittent claudication.     

31P in-vivo spectroscopic study by high-field whole-body MR system--an application to a case with arteriosclerosis obliterans

31P in-vivo spectroscopy was performed by a 1.5-tesla whole-body MR system. The 31P spectrum for the calf muscle in a patient with arteriosclerosis obliterans having intermittent claudication was obtained every two minutes. When the spectrum after the workload was compared with that at rest, an increase in inorganic phosphate (Pi) and a decrease in phosphocreatine (PCr) were observed, resulting in a strong decrease in the PCr/Pi ratio. This method can measure the ischemic and recovery stages of energy metabolism in skeletal muscle noninvasively and continuously in addition to magnetic resonance imaging.     

A case of rapidly progressive glomerulonephritis in the course of Wegener's granulomatosis

Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis of the respiratory tract and glomerulonephritis (GN). Prognosis of this disease is poor and about 20% of untreated patients die after one year from the onset. WG was recognized in 45-year-old patient on the basis of: 1) clinical symptoms (joint pain and swollen, purpura on the skin which appeared one week after respiratory tract infection, ulceration of the tonsils and lingula), 2) results of additional testing (X-chest-ray-infiltrates of both lungs), positive results of the cANCA (titre 1:640) and rapidly progressive renal failure [the increase of serum creatinine level (Pcr) from 123.7 to 707 mumol/l (1.4 to 8.0 mg/dl) during one week]. Renal biopsy revealed extracapillary GN (cellular crescents in 7 out of 8 glomeruli and scattered foci of fibrinoid necrosis of capillary walls in all). At the beginning of the treatment Pcr raised to 884 mumol/l (10 mg/dl) and the patient required hemodialysis. He was treated with methylprednisolone (M) at flash doses of 1000 mg/24 h by three days followed by 125 mg/24 h i.v.--because of peptic ulcer, with cyclophosphamide (C-150 mg/24 h p.p.), with trimetoprim/sulphametoxazole, with pentoxifylline and omeprazol. After six weeks of the treatment in the control kidney biopsy sclerotic changes in 10 out of 13 glomeruli and diffuse interstitial fibrosis were found. However, during the same time, we observed clinical remission of the disease and the decrease of Pcr to 176.8 mumol/l (2 mg/dl). The M dosis was reduced by 5 mg every weeks and the C dosis--to 50 mg (because of the increase of aminotransferase levels) After six months of the treatment Pcr was 132.6 mumol/l (1.5 mg/dl) and CANCA titer was 1:16. In this case of RPGN, despite off the progression of the morphological changes in the kidney, we obtained the clinical remission of the disease and significant decrease of Pcr level. These results suggest that aggressive treatment of WG is justified even in patients with advanced renal failure requiring dialysis and in such patients clinical remission is possible to occur.     

磷酸肌酸后适应联合缺血后适应减轻大鼠心肌缺血再灌注损伤

目的探讨磷酸肌酸后适应联合缺血后适应对大鼠心肌缺血再灌注损伤的影响。方法取健康雄性Wistar大鼠40只,随机分成假手术组(Sham组)、缺血再灌注组(I/R组)、缺血后适应组(IPost组)、磷酸肌酸后适应+缺血后适应组(Pcr+IPost组)各10只,均给予心肌缺血30 min,再灌注120 min处理。再灌注2 h后用比色法测量各组血清肌酸激酶(CK)、乳酸脱氢酶(LDH)、髓过氧化物酶(MPO),ELISA方法检测核因子κB(NF-κB),TTC染色测定心肌梗死面积。结果 IPost组血清CK、LDH、MPO活性和NF-κB以及心肌梗死面积显著低于I/R组,Pcr+IPost组较IPost组各项指标进一步降低(P均<0.05)。结论磷酸肌酸后适应联合缺血后适应可以明显减轻大鼠心肌缺血再灌注损伤,其机制之一可能与抑制NF-κB参与的炎症反应有关。     

Venous claudication. A report of 15 cases and a review of the literature

The symptom of intermittent claudication is not invariably due to arterial disease. Exercise-related pain resulting from venous insufficiency is poorly defined, but has been described by a number of authors in the past. Fifteen patients with symptoms suggestive of venous claudication are reported. The history and clinical findings are described. The further investigation of these patients is outlined, starting with the non-invasive methods of Doppler ultrasonography and strain gauge plethysmography. Ascending phlebography was performed on all affected limbs (n. 19) and descending phlebography was performed on those shown to have a patent deep venous system. These investigations demonstrated deep venous abnormalities associated with the distinct symptom complex. Venous claudication is defined and the literature reviewed. It is hoped that a clearer understanding of the condition will result in more frequent and accurate diagnosis with subsequent benefit to the patient.     

Intermittent arterial claudication. Clinical aspects--hemodynamic correlation

Introduction: Intermittent arterial claudication is the master symptom in lower limbs arteriopathy. It is used as a reference in invasive or non-invasive arterial explorations. It allows to assess the evolutive degree of the disease and above all helps the therapeutic decision. The seat of claudication is traditionally acknowledged as being located immediately downstream of the significant arterial lesion. The purpose of our work was to verify such a notion and ascertain the relation between spontaneous and tread-mill induced claudication. Protocol: 60 stage-2 arteritic patients were included in a prospective mode study. They were all taken in hospital for arteriographic check-up and vascular functional explorations: Doppler velocimetry, segment pressures, treadmill tests and pressure measurements after stress. The patients were classified according to age (table I), time of claudication record (table II) and lesions location (table III). All clinical and paraclinical data were recorded with a view to correlations interpretation. Results and discussion: The relation between spontaneous claudication and tread-mill induced claudication was studied with respect to lesion sites (table IV). Among 37 patients 46% of the claudications observed appeared at iliac stage in both cases (fig. 1). In 35 cases, femoral claudication was observed in 48% (fig. 2). As for distal claudication among 6 patients, 3 showed calf claudication in both cases, i had foot claudication and 2 showed discrepant claudication types. The relation between claudication and lesion site was not confirmed in all cases. Buttock claudication always appeared in relation with a lesion upstream or an internal iliac lesion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ultrasound of proximal upper extremity arteries to increase the diagnostic yield in large-vessel giant cell arteritis

OBJECTIVE: To describe characteristic ultrasound findings and clinical features of patients with newly diagnosed cranial and large-vessel (LV) GCA in a specialized ultrasound clinic. METHODS: This case-control study includes all consecutive patients between 1997 and 2006 with newly diagnosed GCA. Duplex ultrasound of the temporal, subclavian, axillary and proximal brachial arteries was performed in all patients with suspected temporal arteritis, PMR, arm claudication, unclear inflammation or pyrexia of unknown origin (PUO). RESULTS: In 53 of 176 patients, ultrasound depicted characteristic vasculitic homogeneous wall swelling of the axillary, subclavian and/or proximal brachial arteries. These were affected in 98, 61 and 21%, respectively, in the 53 patients. The findings were bilateral in 79%. Axillary arteries were stenotic or occluded in 51 and 2% and temporal artery ultrasound and histology were positive in 62 and 67% of LV-GCA cases, respectively. A significantly greater number of LV-GCA patients were female (83 vs 65%) and younger (mean 66 vs 72 yrs) as compared with those without proximal arm involvement. Headaches (38 vs 75%), jaw claudication (24 vs 48%) and anterior ischaemic optic neuropathy (4 vs 19%) occurred significantly less frequently. The median time until diagnosis was significantly longer (31 vs 8 weeks). ESR and presence of PMR were similar in both groups. CONCLUSIONS: Performing axillary artery ultrasound in all patients with suspected temporal arteritis, PMR, arm claudication, unclear inflammation or PUO increases the diagnostic yield for LV-GCA. Patients with LV-GCA differ from those without arm involvement.     

Acquired skeletal muscle metabolic myopathy in atherosclerotic peripheral arterial disease

Peripheral arterial disease (PAD) is associated with an increased risk of overall cardiovascular mortality, and substantial morbidity resulting from claudication. While the initial disease process is clearly the result of atherosclerosis in the arterial circulation of the limb, altered hemodynamics do not completely explain the pathophysiology of claudication. Work from several laboratories has demonstrated secondary changes in the skeletal muscle of patients with PAD which are consistent with the presence of an acquired metabolic myopathy in these patients. Key findings include an alteration in the expression of mitochondrial enzymes, the accumulation of metabolic intermediates, altered regulation of mitochondrial respiration, increased oxidative stress, and the presence of somatic mutations in the mitochondrial genome. Understanding the metabolic changes associated with PAD is important in understanding the pathophysiology of claudication and in the development of novel therapeutic strategies.     

Claudication does not always precede critical leg ischemia.

Prevalence of intermittent claudication is often used to calculate the prevalence of critical leg ischemia (CLI), a more severe form of peripheral arterial disease (PAD). Although this logical course of the disease is intellectually appealing, not all patients with CLI have experienced any symptoms of previous claudication. A total of 100 consecutive patients with objective evidence of critical ischemia, as evaluated by non-invasive testing in the authors' vascular laboratory, were subjected to a structured interview to evaluate how often peripheral arterial disease is presented with symptoms of CLI as the initial complaint. In all, 37 patients had never experienced claudication prior to the development of CLI. Furthermore, 12 of 63 patients who suffered from previous claudication did not have any claudication symptoms at the time of the development of CLI. Of the 37 patients with CLI as the first sign of PAD, 20 had diabetes--four of whom with manifest diagnosed neuropathy. The patients without previous claudication more frequently had ulcers as the initial symptom of CLI (89%) than those with claudication (59%), whose disease first progressed to rest pain. Altogether, 25 patients did not walk enough to develop symptoms of claudication. In conclusion, every patient presenting with symptoms potentially related to CLI should undergo vascular laboratory measurements regardless of whether he/she has a history of claudication or not. This is especially true in limbs with unhealed skin lesions.     

Abnormal circulating levels of metalloprotease 9 and its tissue inhibitor 1 in angiographically proven peripheral arterial disease: relationship to disease severity

BACKGROUND: Peripheral arterial disease (PAD) is associated with adaptive changes in the vascular and muscle extracellular matrix (ECM) in response to reduced blood flow. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), are key modulators of ECM turnover. We hypothesized that patients with intermittent claudication (with low ankle-brachial blood pressure index, <0.8), and critical ischaemia would have raised circulating levels of MMP-9, TIMP-1 and TIMP-2 compared with healthy controls, reflecting an increase in proteolytic activity which may be related to ECM turnover in PAD. METHODS: We studied 36 patients (23 males; 65 +/- 9 years) with intermittent claudication and 43 (25 males; 68 +/- 12) patients with critical ischaemia. All patients had angiographic evidence confirming significant PAD. RESULTS: Circulating levels of MMP-9 and TIMP-1 were higher (both P < 0.0001) in the PAD patient groups compared with the controls. Patients with critical ischaemia had MMP-9 and TIMP-1 levels that were significantly higher than those with intermittent claudication. There were no differences in circulating TIMP-2 levels between patients and controls. There was a modest positive correlation between the white cell count (WCC) and MMP-9, both patients with intermittent claudication (Spearman, r = 0.398, P = 0.016) and critical ischaemia (r = 0.378, P = 0.014). CONCLUSION: We demonstrate higher levels of circulating MMP-9 and TIMP-1 in patients with intermittent claudication and critical ischaemia. Circulating concentrations of both markers can be related to disease severity, being higher in critical ischaemia compared with levels in intermittent claudication.     

A long-term study of policosanol in the treatment of intermittent claudication

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. This study was undertaken to investigate the long-term effects of policosanol administered to patients with moderately severe intermittent claudication. The study consisted of a 6-week single-blind, placebo-controlled run in phase, followed by a 2-year double-blind, randomized treatment step. Fifty-six patients who met study entry criteria were randomized to receive placebo or policosanol 10 mg twice daily. Walking distances on a treadmill (constant speed 3.2 km/h, slope 10 degrees, temperature 25 degrees C) were assessed before and after 6, 12, 18, and 24 months of treatment. Both groups were similar at randomization. After 6 months of therapy, policosanol significantly increased (p < 0.01) the initial claudication distance from 125.9 +/- 8.7 m to 201.1 +/- 24.8 m and the absolute claudication distance from 219.5 +/- 14.1 m to 380.7 +/- 50.2 m. Both variables remained unchanged in the placebo group (p < 0.01). These effects did not wear off but improved after long-term therapy, so that final values were 333.5 +/- 28.6 m (initial claudication distance) and 648.9 +/- 54.1 m (absolute claudication distance); both significantly greater (p < 0.0001) than those obtained in the placebo group, which showed values of 137.9 +/- 21.8 m (initial claudication distance) and 237.7 +/- 28.1 m (absolute claudication distance), respectively. At study completion, 21 policosanol and 5 placebo patients attained increases in claudication distance values > 50% (p < 0.001). Policosanol, but not placebo, significantly increased the ankle/arm pressure index. In addition, from month 6 up to study completion, the frequency of patients reporting improvement of lower limb symptoms was greater in the policosanol group than in the placebo group. The treatment was tolerated well. There were 16 withdrawals (12 placebo, 4 policosanol) from the study. Eight patients in the placebo group experienced a total of 10 serious adverse events, 8 of which were vascular events, compared with none in the policosanol group (p < 0.01). In addition, 3 patients in the policosanol group and 3 patients in the placebo group reported mild adverse events during the study. The present results demonstrate the long-term usefulness of policosanol therapy to treat patients with intermittent claudication.     

Treadmill testing in the assessment of peripheral arterial disease

A treadmill exercise test is used in many vascular laboratories to measure the claudication time and the total walking time of patients with intermittent claudication. Three hundred and nine consecutive outpatients in the peripheral arterial disease clinic were assessed on the treadmill. Fifty-nine were unable to walk on it at all, and of the remaining 250 patients, 68 (27%) could manage five minutes of treadmill exercise, and 87 (35%) patients stopped for reasons other than intermittent claudication. Only 95 (38%) stopped walking within five minutes as a result of intermittent claudication. Fifty of these 95 patients were retested approximately 10 days later and the mean change from day 1 to day 2 in the claudication time and in the total walking time was calculated to establish the normal range. From these results, if a treadmill is to be used to infer any improvement, we calculate that the claudication time must increase by at least 63 seconds and the total walking time by 93 seconds. Treadmill testing for the assessment of symptoms, if it is used at all, should be used in conjunction with objective methods of assessment.     

Hepatic phosphorus-31 magnetic resonance spectroscopy in primary biliary cirrhosis and its relation to prognostic models.

BACKGROUND: In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) provides biochemical information about phosphorus metabolism. AIM: To assess 31P MRS as a prognostic marker in patients with primary biliary cirrhosis (PBC) in relation to the current clinical prognostic models. PATIENTS AND METHODS: Twenty three patients with PBC of varying functional severity and 16 matched healthy volunteers were studied using in vivo 31P MRS. Spectra were acquired using a 1.5 T spectroscopy system. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) and nucleotide triphosphate (NTP) were calculated. Pugh score, Christensen prognostic index, and R value according to the Mayo model were calculated from the clinical data. RESULTS: The PME/NTP, Pi/NTP, PME/PDE, and PME/Pi ratios and the PME signal height ratio (SHR) were significantly higher, while the PDE/NTP and PDE/SHR were significantly lower in PBC patients compared with healthy volunteers (p < 0.01). Significant correlations were seen between PME/Pi ratio and the prognostic index according to Christensen (r = 0.63, p < 0.001), R value according to the Mayo model (r = 0.45, p < 0.03), and with the Pugh score (r = 0.55, p < 0.007). CONCLUSIONS: This study shows that PME/Pi ratio obtained from 31P MRS correlates well with all three of the commonly used models of prognosis in patients with PBC. A longitudinal study with larger number of patients is required to confirm these findings and elucidate the biochemical changes underlying this phenomenon.     

Functional outcomes and quality of life in peripheral arterial disease: current status

This review examines current evidence for baseline functional impairment and changes with therapy in patients with peripheral arterial disease (PAD)--ranging from patients without claudication or critical limb ischemia (CLI) but other exertional leg symptoms (erroneously referred to as asymptomatic in the Fontaine classification system), to patients with claudication and those with CLI. The review points out that the status of functional outcomes research is markedly different in focus and development in the different levels of disease severity--paradoxically less studied in the more severe CLI population than in patients with claudication, for example.     

β-Blockers in patients with intermittent claudication and arterial hypertension: results from the nebivolol or metoprolol in arterial occlusive disease trial

The use of β-receptor blockers in peripheral arterial disease is controversial for their impact on vasomotor tone. The β-blocker nebivolol possesses vasodilating, endothelium-dependent, NO-releasing properties that might be beneficial in peripheral arterial disease. The aim of the study was to evaluate the effects and tolerability of nebivolol in comparison with metoprolol in these patients. A total of 128 patients with intermittent claudication and essential hypertension were included and double-blind randomized to receive 5 mg of nebivolol (N=65) or 95 mg of metoprolol (N=63) once daily. End points were changes in ankle-brachial index, initial and absolute claudication distance, endothelial function assessed by flow-mediated dilatation of the brachial artery, blood pressure, and quality of life using the claudication scale questionnaire. End point analysis was possible in 109 patients (85.2%). After the 48-week treatment period, ankle-brachial index and absolute claudication distance improved significantly in both patient groups (P<0.05 for both), with no difference across treatments. A significant increase of initial claudication distance was found in the nebivolol group. Adjusted mean change of initial claudication distance was 33.9% after nebivolol (P=0.003) and 16.6% after metoprolol (P=0.12) treatment. Quality of life was not influenced by either treatment, and there was no relevant change in flow-mediated dilatation in patients treated with nebivolol or metoprolol (P=0.16). Both drugs were equally effective in lowering blood pressure. In conclusion, β-blocker therapy was well tolerated in patients with intermittent claudication and arterial hypertension during a treatment period of ≈1 year. In the direct comparison, there was no significant difference between nebivolol and metoprolol.     

Long-term effects of supervised exercise training on walking capacity and quality of life in patients with intermittent claudication

Supervised exercise training has been shown to improve walking capacity in several studies of patients with intermittent claudication. However, data on long-term outcome are quite limited. The aim of this prospective study was to evaluate long-term effects of supervised exercise training on walking capacity and quality of life in patients with intermittent claudication. Patients and methods: Sixty-seven consecutive patients with intermittent claudication who completed a supervised 12-week exercise training program were asked for follow up evaluation 39 +/- 20 months after program completion. Pain-free walking distance (PWD) and maximum walking distances (MWD) were assessed by treadmill test and several questionnaires. Results: Forty (60%) patients agreed to participate, 22 (33%) refused participation, and 5 (7%) died during follow-up. PWD and MWD significantly improved at completion of 12-weeks supervised exercise training as compared to baseline (PWD 114 +/- 100 vs. 235 +/- 248, p = 0.002; MWD 297 +/- 273 vs. 474 +/- 359, p = 0.001). Improvement of PWD and MWD could be maintained at follow up (197 +/- 254, p = 0.014; 390 +/- 324, p = 0.035, respectively) with non-smokers showing significantly better sustained PWD and MWD improvement as compared to baseline. Overall, walking capacity correlated with functional status of quality of life. Conclusions: Major findings of this investigation were that improvement in walking capacity is sustained after completion of supervised exercise training program with best results in patients who quitted or never smoked. Improved walking capacity is associated with increased functional status of quality of life.     

Exaggerated endothelin release in response to acute mental stress in patients with intermittent claudication

Endothelin-1 (ET-1) is an endothelial-derived 21-amino-acid peptide with potent vasoconstrictor and mitogenic properties implicated in several cardiovascular disorders. To evaluate the plasma ET-1 response to mental stress in patients with intermittent claudication, plasma endothelin concentrations were measured by radioimmunoassay in 15 claudicant outpatients (13 men and 2 women; mean age 62 +/- 4 years) and in 15 sex- and age-matched healthy control subjects (12 men and 3 women; mean age 60 +/- 8 years) before and after mental arithmetic performed for 10 minutes. Venous blood samples were drawn from an antecubital vein at baseline, at the end of the mental arithmetic, and at 10 minutes of recovery. Baseline ET-1 values were higher in patients with intermittent claudication as compared with control subjects (4.5 +/- 0.5 pmol/L and 2.2 +/- 0.3 pmol/L, respectively, p < 0.0001). At the end of mental stress, ET-1 levels rose significantly in both groups from baseline (p < 0.001) reaching a higher value in patients with intermittent claudication than in control subjects (5.6 +/- 0.7 pmol/L and 2.4 +/- 0.4 pmol/L, respectively, p < 0.0001). The percent increases (delta%) in ET-1 plasma concentrations from baseline in response to mental stress were significantly greater in claudicant patients than in control subjects (+23 +/- 9% and +9 +/- 7%, respectively, p < 0.0001). ET-1 plasma concentrations returned to baseline values similarly in both groups at minute 10 of the recovery period. These findings show that acute mental stress causes an exaggerated release of ET-1 in patients with intermittent claudication and suggest that this could be a potential pathophysiological mechanism through which mental stress may trigger adverse acute cardiac events and accelerate progression of atherosclerosis in these patients.