3-min step test and treadmill exercise for evaluating exercise-induced asthma.

A simple exercise test would be useful for detecting exercise-induced asthma, a common problem in asthmatic children. The current study compared the 3-min step test with treadmill exercise for evaluating exercise-induced asthma in asthmatic children and assessed whether responses to both tests are influenced by baseline lung function and habitual physical activity. A series of 154 asthmatic children (84 male children; mean age 12.9 +/- 0.9 yrs) underwent a 3-min step-test and treadmill testing on different days within a week at least 24 h apart. Before both tests each subject did spirometry to obtain the baseline forced expiratory volume in one second (FEV1). After both exercise challenges all subjects did serial spirometry and the lowest FEV1 recorded over time was used to calculate the fall in FEV1 expressed as a percentage of the measured pre-exercise (baseline) value (% fall in FEV1) and the area above the FEV1 curve (AAC0-30 min) expressed as a percentage of the pre-exercise value. Changes in both exercise variables were also analysed in percentile subgroups defined by questionnaire answers on habitual physical activity in hours. The mean % fall in FEV1 was significantly higher for treadmill exercise than for the step test (15.0 +/- 7.5 versus 11.7 +/- 5.9); and the AAC0-30 min was larger for treadmill than for the step test (-261.6 +/- 139.9% versus -197.3 +/- 105.0% min). In all subgroups defined by habitual physical activity the mean % fall in FEV1 decreased more after treadmill exercise than after the step test. After step test and treadmill exercise no significant correlation was found between % fall in FEV1 and baseline lung function, or between % fall in FEV1 among groups defined by habitual physical activity. Although the 3-min step test yields a lower % fall in forced expiratory volume in one second (FEV1) and a lower value of the area above the FEV1 curve than treadmill testing, it is a quick, economical, reproducible and portable alternative procedure for identifying exercise-induced asthma in outpatients and epidemiological studies. Baseline lung function and habitual physical activity have no influence on the amount or duration of exercise-induced asthma.     

Increased exercise tolerance after nitroglycerin oral spray: a new and effective therapeutic modality in angina pectoris

The prophylactic antianginal efficacy of nitroglycerin (NTG) oral spray was assessed in 20 patients with angiographically documented coronary disease and stable angina pectoris. The evaluation was by a randomized crossover trial involving treadmill exercise testing. On study day 1, a control treadmill exercise test was performed, followed 30 minutes later by a second exercise test 2 minutes after administration of either placebo (group A, 10 patients) or NTG spray 0.8 mg (group B, 10 patients). One week later, on study day 2, the patients again underwent control treadmill exercise testing followed by a second exercise test after either NTG spray (group A) or placebo (group B). NTG spray delayed the onset of anginal pain during exercise by a mean of 100 +/- 64 seconds (p less than 0.001) in 13 patients and prevented pain entirely in seven. Placebo did not significantly delay the appearance of angina and prevented chest pain in only one patient. NTG spray increased treadmill exercise duration by 31% before the onset of angina (p less than 0.001); placebo did not significantly alter the duration of exercise. NTG spray abolished in six patients and delayed in 14 patients the onset of exercise-induced ST-segment depression of 1 mm (p less than 0.001). Patients achieved a higher heart rate at peak exercise with NTG spray, and yet the maximal exercise-induced ST-segment depression of 2.1 +/- 1.0 mm during the control study declined to 1.3 +/- 0.9 mm on NTG spray (p less than 0.001). Placebo had no effect on exercise ST-segment depression. These data indicate that the oral NTG spray is an effective prophylactic for exercise-induced angina.     

Superiority of endothelin-1 over norepinephrine in exercise-induced alterations of the conduit artery tone of the non-exercised arm in patients with chronic heart failure

This study is aimed at examining the relative importance of norepinephrine and endothelin-1 in treadmill exercise-induced changes in brachial arterial tone of the non-exercised arm in patients with chronic heart failure (CHF). Brachial artery diameter and blood flow were measured before and after exercise in eight healthy volunteers and 18 patients with stable chronic heart failure by high-resolution ultrasound. Maximal exercise resulted in brachial artery dilatation in controls (4.42+/-0.39 vs. 4.77+/-0.39 mm; P<0. 0001) in contrast to constriction seen in the patients (5.27+/-0.67 vs. 5.12+/-0.66 mm; P=0.07). Both groups demonstrated a significant increase in blood flow after exercise. The pre-exercise (2.83+/-0.76 vs. 1.69+/-0.15 pmol/l; P=0.0004), post-exercise (4.15+/-1.5 vs. 2. 02+/-0.34 pmol/l; P=0.0004) and the percent increase (47.15+/-32.5 vs. 19.0+/-10.5%; P=0.02) in endothelin-1 levels were significantly greater in patients than in controls. In contrast to endothelin-1, the exercise-induced percent increase in norepinephrine was greater in controls than patients (100.7+/-51.8 vs. 49.8+/-43.4%; P=0.01). The percent change in the diameter of the brachial artery in response to maximal exercise was significantly correlated to pre- (r=0.634; P=0.003) and post-exercise (r=0.467; P=0.05) endothelin-1 levels in patients but not in controls [pre-exercise (r=0.07; P=0. 86), post-exercise (r=0.310; P=0.47)]. The change in the diameter of the brachial artery did not correlate with pre- or post-exercise plasma norepinephrine levels in either group. These findings suggest that endothelin-1 is potentially more important than norepinephrine in contributing exercise-induced brachial artery constriction in patients with chronic heart failure.     

Supervised exercise training reduces plasma levels of the endothelial inflammatory markers E-selectin and ICAM-I in patients with peripheral arterial disease

Elevated plasma levels of vascular inflammatory markers have been reported in patients with peripheral arterial disease (PAD). We assessed the effect of supervised exercise training (ET) on vascular inflammation, hypothesizing that ET reduces plasma levels of the endothelial adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-I (VCAM-I). Twenty-nine patients with PAD underwent a supervised ET program for 8 weeks. Before and after ET, walking distances (pain-free, PWD; maximal, MWD) were determined by a standard treadmill test. Plasma levels of E-selectin and ICAM-I were significantly reduced (E-selectin: 45.5-40.4 ng/mL, P = .013); ICAM-I: 342.0-298.0 ng/mL, P = .016). VCAM-1 levels were unchanged. Walking distances increased significantly (PWD: median 77-150 m, P < .001; MWD: median 306-535 m, P < .001). In conclusion, 8 weeks of ET in patients with PAD reduces plasma levels of the specific endothelium-derived inflammatory markers E-selectin and ICAM-I.     

An evaluation of levalbuterol HFA in the prevention of exercise-induced bronchospasm.

BACKGROUND: Exercise-induced bronchospasm (EIB) affects up to 90% of all patients with asthma. Objective. This study evaluated the ability of levalbuterol hydrofluoroalkane (HFA) 90 mug (two actuations of 45 microg) administered via metered dose inhaler (MDI) to protect against EIB in mild-to-moderate asthmatics. METHODS: This was a randomized, double-blind, placebo-controlled, two-way cross-over study. Patients with asthma (n = 15) were > or =18 years, had a > or =6-month history of EIB, > or = 70% baseline predicted forced expiratory volume in 1 second (FEV1), and a 20% to 50% decrease in FEV(1) after treadmill exercise challenge using single-blind placebo MDI. Levalbuterol or placebo was self-administered 30 minutes before exercise. Treatment sequences were separated by a 3-to 7-day washout period. Spirometry was performed predose, 20 minutes postdose/pre-exercise, and 5, 10, 15, 30, and 60 minutes post-exercise. The primary endpoint was the maximum percent decrease in FEV1 from baseline (postdose/pre-exercise). The percentage of protected (< or = 20% decrease in post-exercise FEV1) patients was also assessed. RESULTS: Levalbuterol had significantly smaller maximum percent post-exercise decrease in FEV1 compared with placebo (LS mean +/- SE; -4.8% +/- 2.8% versus -22.5% +/- 2.8%, respectively). For levalbuterol, 14/15 (93.3%) patients had < 20% decrease in post-exercise FEV1 compared with 8/15 (53.3%) for placebo (p = 0.0143). Treatment was well tolerated. CONCLUSION: Levalbuterol HFA MDI (90 microg) administered 30 minutes before exercise was significantly more effective than placebo in protecting against EIB after a single exercise challenge and was well tolerated. CLINICAL IMPLICATIONS: Levalbuterol HFA MDI when administered before exercise was effective in protecting adults with asthma from EIB.     

Effects of a selective thromboxane synthetase inhibitor (OKY-046) in patients with coronary artery disease during exercise

We studied the levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), platelet aggregability, beta-thromboglobulin and platelet factor 4 in 30 coronary artery disease (CAD) patients and 21 normal subjects during exercise. During treadmill exercise, 13 of 30 CAD patients reported chest pain. We administered a selective thromboxane synthetase inhibitor (OKY-046) for 2 weeks to 10 CAD patients with exercise-induced chest pain and studied its effects. At rest, the plasma TXB2 levels and platelet aggregation were significantly lower in normal subjects than in CAD patients, and there was no difference between CAD patients with and without exercise-induced chest pain. On treadmill testing, plasma TXB2 levels and platelet aggregation increased significantly only in the CAD patients with exercise-induced chest pain. Plasma 6-keto-PGF1 alpha levels in normal subjects were significantly higher than those in CAD patients both at rest and during exercise. After administration of OKY-046, mean exercise time increased significantly from 7.5 to 8.6 min (p less than 0.001). Plasma TXB2 level and platelet aggregation decreased significantly after OKY-046 administration both at rest and during exercise. These results suggest that a marked increase in TXA2, with only a minimal change in PGI2, during exercise may contribute to exercise-induced myocardial ischemia, and that OKY-046 is useful in the treatment of CAD patients.     

A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge

OBJECTIVES: To compare the effects of addition of montelukast or salmeterol to inhaled corticosteroids (ICS) on the response to rescue beta2-agonist use after exercise-induced bronchoconstriction. METHODS: A double-blind, placebo-controlled study was performed at 16 centers in the United States. Patients with asthma (n = 122, ages 15-58) whose symptoms were uncontrolled on Low-dose inhaled fluticasone and who had a history of exercise-induced worsening of asthma were randomized to receive either montelukast (10 mg once daily), salmeterol (50microg twice daily), or placebo for 4 weeks. Standardized spirometry after exercise challenge and beta2-agonist rescue was performed at baseline, week 1 and 4. RESULTS: Maximum achievable forced expiratory volume in 1 s (FEV1) percent predicted after rescue beta2-agonist improved in the montelukast (+1.5%) and placebo (+1.2%) groups at 4 weeks, but diminished in the salmeterol (-3.9%) group (P < 0.001). Although pre-exercise FEV1 was greatest with salmeterol (P = 0.10), patients taking montelukast had significantly greater protection from an exercise-induced decrease in FEV1 than those taking salmeterol (P < 0.001). Both the magnitude and rate of rescue bronchodilation were greater with montelukast compared with salmeterol (P < 0.001). Five minutes after rescue beta2-agonist, 92% of patients taking montelukast and 68% of those taking placebo had recovered to pre-exercise levels, whereas only 50% of those taking salmeterol had recovered to pre-exercise levels. CONCLUSION: In patients whose asthma symptoms remain uncontrolled using ICS, addition of montelukast permits a greater and more rapid rescue bronchodilation with a short-acting beta2-agonist than addition of salmeterol and provides consistent and clinically meaningful protection against exercise-induced bronchoconstriction.     

Efficacy and safety of oral nadolol for exercise-induced ventricular arrhythmias

Sixty-four patients with reproducible exercise-induced ventricular arrhythmias were enrolled in an open-label, multicenter study to assess the efficacy and safety of oral nadolol therapy. There were 53 men and 11 women ranging in age from 19 to 75 years (mean 53.9). The severity of arrhythmias varied from frequent ventricular premature beats to nonsustained and sustained ventricular tachycardias. Using serial treadmill exercise tests, patients underwent dose titration for 1 month and were followed up for 3 to 6 months. Depending on drug tolerance and response to treadmill exercise testing, the single daily required dose of oral nadolol ranged from 20 to 240 mg (average 66). Twenty-three (36%) of the patients experienced a total of 30 adverse effects of nadolol therapy; however, only 9 (14%) patients had to be withdrawn from the study. The adverse effects observed were those commonly associated with beta-adrenergic blocking agents, and all were dose-dependent and reversible. At the last patient visit, the severity of exercise-induced ventricular arrhythmias was significantly decreased compared with pretreatment in 36 (75%) of 48 evaluable patients. Eighteen (38%) of the patients demonstrated total suppression of arrhythmias. This was accompanied by significant increases from pretreatment in both the mean duration of symptom-limited exercise (+1.02 +/- 0.41 minutes, p less than 0.05) and the mean time of exercise required for arrhythmia induction (+1.80 +/- 0.66 minutes, p less than 0.01), a significant decrease from pretreatment in the mean peak exercise double-product (-4,775, p less than 0.001) and a decrease in the incidence of exercise-induced ST-segment depression (-33%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Peripheral vascular disease. Rheologic variables during controlled ischemia

The quantitative and qualitative behavior of hemorheologic factors both at rest and after treadmill exercise in 30 male patients with stage II peripheral vascular disease compared with 20 sex- and age-matched healthy controls have been studied. The aim of our study was to identify functional rheologic markers for peripheral vascular disease. At rest, whole blood viscosity (corrected for hematocrit at both high and low shear rates), fibrinogen levels (4.23 +/- 1.39 vs. 3.23 +/- 1.5), and white blood cell count (7.05 +/- 1.25 vs. 6.03 +/- 1.28) were significantly different between patients and controls. After treadmill exercise, white blood cell counts increased in both patients and controls, whereas only the filterability of mononuclear leukocytes showed a significant variation in the patient group (5.47 +/- 1.54 vs. 7.26 +/- 2.00, p less than 0.002). In this group, mononuclear filterability improved during the recovery period. The results suggest a relation between exercise-induced ischemia of the lower limb and mononuclear filterability in patients with peripheral vascular disease. Mononuclear filterability could be a functional rheologic marker for peripheral vascular disease.     

Long-term angiotensin-converting enzyme inhibition reduces plasma asymmetric dimethylarginine and improves endothelial nitric oxide bioavailability and coronary microvascular function in patients with syndrome X

Angiotensin-converting enzyme (ACE) inhibition has been shown to improve clinical myocardial ischemia in patients with syndrome X (angina pectoris, positive treadmill exercise test, normal coronary angiograms, and no evidence of coronary spasm). This study was conducted to investigate the effects of long-term ACE inhibitors on endothelial nitric oxide (NO) metabolism and coronary microvascular function in patients with syndrome X. After a 2-week washout period, 20 patients with syndrome X were randomized to receive either enalapril, an ACE inhibitor, 5 mg twice daily (n = 10) or placebo (n = 10) in a double-blind design for 8 weeks. Another 6 age- and gender-matched subjects with negative treadmill exercise tests were also studied as controls. Compared with control subjects, patients with syndrome X had significantly reduced coronary flow reserve, reduced plasma levels of nitrate and nitrite (NOx), and a reduced plasma L-arginine to asymmetric dimethylarginine (ADMA) ratio (an index of systemic NO metabolism), as well as reduced endothelial function. These patients also had increased plasma levels of ADMA, which is an endogenous inhibitor of NO synthase and of von Willebrand factor, a marker of endothelial injury. Baseline characteristics including exercise performance and coronary flow reserve were similar between enalapril and placebo groups. After an 8-week treatment period, exercise duration (p = 0.001) and coronary flow reserve (p = 0.001) significantly improved with enalapril but not with placebo. Enalapril treatment, but not placebo, reduced plasma von Willebrand factor (p = 0.03) and ADMA levels (p = 0.01) and increased NOx levels (p = 0.01) and the ratio of L-arginine to ADMA (p <0.01). In patients with syndrome X, the plasma NOx level was positively and ADMA level inversely correlated with coronary flow reserve before and after the treatment. In conclusion, long-term ACE inhibitor treatment with enalapril improved coronary microvascular function as well as myocardial ischemia in patients with syndrome X. This may be related to the improvement of endothelial NO bioavailability with the reduction of plasma ADMA levels.     

培哚普利和依那普利对ApoE基因敲除小鼠动脉粥样硬化进展的影响

目的 探讨血管紧张素转换酶抑制剂(ACEI)对ApoE基因敲除小鼠动脉粥样硬化病变进程的影响,特别是对斑块成分的影响,并比较培哚普利与依那普利的疗效.方法 ApoE基因敲除小鼠随机分为培哚普利组、依那普利组及对照组3组.对主动脉根部斑块进行定量分析,并评估斑块胶原含量及脂核面积.以冰冻切片进行免疫荧光检查,观察斑块内单核细胞/巨噬细胞-2(MOMA-2)、细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子(VCAM-1)、基质金属蛋白酶-9(MMP-9)的表达.结果 各实验组之间的血压、血脂差异无统计学意义.与对照组比较,培哚普利组与依那普利组的斑块面积分别少了25.33%和22.86%(P均＜0.01),但是两组ACEI的斑块面积差异无统计学意义.培哚普利组与依那普利组减小脂核面积(分别为52.98%及38.98%,P均＜0.01)及MOMA-2(分别为88.38%及52.16%,P均＜0.01)、ICAM-1(分别为80.87%及49.59%,P均＜0.01)、VCAM-1(分别为77.56%及56.44%,P均＜0.01)、MMP-9(分别为86.93%及55.56%,P均＜0.01)的表达,并增加斑块胶原含量(分别为298.36%及168.14%,P均＜0.01),而且培哚普利组在这些方面均显著优于依那普利组(P均＜0.05).结论 ACEI在不影响血脂和血压的情况下可以抑制ApoE基因敲除小鼠动脉粥样硬化斑块的炎症并延缓动脉粥样硬化的进展.尽管培哚普利和依那普利在减少斑块面积方面差异无统计学意义,但是培哚普利在稳定斑块方面优于依那普利.     

The changes in circulating levels of vasoactive intestinal polypeptide during exercise and its reproducibility for detection of myocardial ischemia

Vasoactive intestinal polypeptide (VIP) contributes to the regulation of coronary vasomotor tone and circulating levels of VIP have been reported to increase during acute myocardial infarction. However, the changes in VIP concentration during exercise-induced ischemia have not been studied yet. Therefore, we sought to determine whether circulating levels of VIP change during treadmill exercise testing and whether they could be used as a marker of exercise-induced myocardial ischemia. Twenty-nine subjects with definitive positive (group-I) and 20 subjects (group-II) with negative results on treadmill exercise testing were included in this study. In order to assess circulating levels of VIP, blood samples were collected in both groups before exercise, at 5 minutes of exercise, at peak exercise, and at 10 minutes in the recovery period. There were no differences between the two groups with respect to the baseline demographics of age, sex, heart rate, or blood pressure. The metabolic equivalents (METs) values, peak heart rate achieved, peak systolic-diastolic blood pressure, and exercise duration did not differ between the two groups. No significant differences were found in the circulating levels of VIP at any stage of the exercise between the two groups (10.5 +/- 2.5 versus 11.0 +/- 3.5 pmol/L, P = 0.5, 10.6 +/- 2.3 versus 10.6 +/- 3.3 pmol/L, P = 0.9, 10.9 +/- 3.1 versus 11.5 +/- 3.4 pmol/L, P = 0.5, and 10.7 +/- 1.8 versus 11.7 +/- 4.1 pmol/L, P = 0.3, respectively). There was no relationship between the circulating level of VIP and exercise-induced myocardial ischemia, and therefore it could not be used as a marker of exercise-induced myocardial ischemia.     

Soluble vascular cell adhesion molecule-1 (sVCAM-1) is an independent prognostic marker in Hodgkin's disease

Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1, sCD106) were significantly elevated in patients with Hodgkin's disease (HD) (n = 101) compared to controls (n = 31) (P < 0.0001). sVCAM-1 correlated with histology, stage, B-symptoms, and prognostic markers (sICAM-1, sCD30, sIL-2R, LDH). sVCAM-1, sICAM-1 and sCD30 added independent prognostic information for both disease-free and overall survival. 14 biopsies from 13 patients with HD were immunostained for VCAM-1 and ICAM-1. The vascular endothelium stained positive for VCAM-1 in 10/12 evaluable biopsies and for ICAM-1 in all evaluable biopsies. A stromal expression of both adhesion molecules precluded a precise evaluation of HRS-cells. This led us to investigate VCAM-1 (and ICAM-1) expression in six Hodgkin cell lines (HDLM-2, L428, L540, L591, DEV, KM-H2). Two cell lines stained positive for VCAM-1 (HDLM-2, L591). All cell lines stained positive for ICAM-1. sVCAM-1 is a new prognostic marker in HD; its predictive power equals or surpasses that of sCD30 and sICAM-1. Furthermore, two Hodgkin cell lines stained positive for VCAM-1. This indicates that VCAM-1 may be expressed by some HD tumour cells in vivo.     

Effect of propionylcarnitine on changes in endothelial function and plasma levels of adhesion molecules induced by acute exercise in patients with intermittent claudication

In patients with intermittent claudication, treadmill exercise may cause acute deterioration of endothelial function and increase in plasma concentrations of adhesion molecules. The authors evaluated the efficacy of intravenously administered propionylcarnitine (PLC)in preventing these phenomena. Thirty-six claudicants with postexercise decrease in brachial artery flow-mediated dilation (FMD)were randomized to either placebo or PLC (600 mg as a single bolus followed by 1 mg/kg/min for 60 minutes).In the 18 patients randomized to placebo, FMD markedly decreased with exercise before (from 6.8 +/-0.4% to 4.0 +/-0.4%; p < 0.001) and after treatment (from 6.5 +/-0.4% to 4.4 +/-0.5%; p < 0.001). By contrast, in the PLC group, FMD significantly decreased with exercise before treatment (from 8.0 +/-0.7% to 4.4 +/-0.4%; p < 0.001), but not after active drug administration (from 7.1 +/-0.7% to 6.0 +/-0.6%; p = 0.067). The difference between treatments was not significant (p = 0.099; ANOVA). However, in the PLC group, the authors found that the greater the exercise-induced deterioration in endothelial function before treatment, the greater the capacity of PLC to prevent a postexercise decrease in FMD (r = -0.50, p = 0.034). Accordingly, they analyzed data in the 19 patients with a baseline exercise-induced decrease in FMD >or=45% (ie, the median FMD reduction in the entire group of 36 patients), and found that the exercise-induced FMD decrease was less after PLC than after placebo (p = 0.046, ANOVA). In the same subgroup, the exercise-induced increase in plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) was significantly higher before than after treatment in patients randomized to PLC (23.4 +/-5% vs 15.3 +/-7%, p = 0.007). In conclusion, in patients with intermittent claudication suffering from a greater endothelial derangement after treadmill, PLC administration provided a protective effect against deterioration of FMD and increase of sVCAM-1 induced by exercise.     

Association of blood pressure and fitness with levels of atherosclerotic risk markers pre-exercise and post-exercise

BACKGROUND: Physical fitness may attenuate the increased atherosclerotic risk in patients with systemic hypertension. We investigated the association of screening blood pressure (BP) and cardiorespiratory fitness with baseline levels and exercise-induced changes in levels of soluble atherosclerotic risk markers. METHODS: Twenty-six otherwise healthy and unmedicated subjects with elevated BP (systolic BP and/or diastolic BP > or =130/85 mm Hg) and 40 subjects with normal BP underwent 20-min treadmill exercise at 65% to 70% of predetermined peak oxygen consumption (VO(2peak)). Interleukin (IL)-6, soluble intercellular adhesion molecule (sICAM)-1, von Willebrand factor (VWF) antigen, and plasminogen activator inhibitor (PAI)-1 antigen were measured at baseline (ie, pre-exercise), early postexercise, and late postexercise (ie, 25 min after exercise). RESULTS: At baseline, higher screening mean arterial BP (MAP) independently predicted higher sICAM-1 levels (P = .031), and lower VO(2peak) independently predicted higher IL-6 (P = .016) and PAI-1 (P < .001) levels. Early and late postexercise lower VO(2peak) was associated with higher mean PAI-1 (P < or = .072) and IL-6 (P < or = .026) levels, and higher screening MAP was associated with higher mean sICAM-1 levels (P < or = .035). Higher VO(2peak) was associated with a greater PAI-1 increase from baseline to early postexercise in subjects with elevated BP (P = .045) but not in those with normal BP. CONCLUSIONS: Circulating levels of some atherosclerotic risk markers at baseline and with exercise were higher with elevated BP and lower with better fitness. Greater fitness did not particularly protect subjects with elevated BP from potentially harmful responses of atherosclerotic risk markers to acute physical exercise.     

Exercise echocardiography: a clinically practical addition in the evaluation of coronary artery disease

There has been only modest clinical interest in exercise echocardiography because of the technical limitations of the procedure. Recognizing that there have been recent technical advances in the echocardiographic instruments and that echocardiography should, in theory, be an ideal technique for evaluating exercise-induced wall motion abnormalities, a clinically practical method of performing exercise echocardiograms was developed. By obtaining the echocardiograms immediately after treadmill exercise, with the patient sitting at the treadmill, a high percent of studies adequate for interpretation was obtained (92%). The addition of echocardiography to the treadmill exercise test significantly enhanced the diagnostic yield. In addition, in cases of one and three vessel disease, exercise echocardiography identified stenosis in specific coronary arteries. In patients with two vessel disease and left circumflex obstruction, specific vessel identification was less reliable. A high percent of patients with multivessel disease developed wall motion abnormalities with exercise that persisted for at least 30 minutes. It is concluded that echocardiography performed immediately after exercise with the new generation of echocardiographs can be a practical and useful clinical tool.     

Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 serum level in patients with chest pain and normal coronary arteries (syndrome X)

BACKGROUND: Plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) mediators of leukocyte adhesion to vascular endothelium may implicate in the pathogenesis of the syndrome of chest pain with normal coronary arteries. HYPOTHESIS: We attempted to determine whether markers of endothelial activation are raised in patients with chest pain and normal coronary arteries. METHODS: We measured plasma VCAM-1, ICAM-1 (ng/ ml) in 36 patients (34 men, 2 women, aged 62 +/- 9 years) with stable angina, coronary artery disease (CAD), and a positive response to exercise test; in 21 patients (6 men, 15 women, aged 56 +/- 9 years) with chest pain and normal coronary arteriograms (syndrome X); and in 11 healthy control subjects (8 men, 3 women, aged 49 +/- 14 years). RESULTS: Plasma ICAM-1 levels were significantly higher both in patients with CAD (mean +/- standard error of the mean) (328 +/- 26, p < 0.05), and in syndrome X (362 +/- 22, p < 0.01) than in controls (225 +/- 29). VCAM-1 levels were also higher in syndrome X (656 +/- 42 ng/ml) and in patients with CAD (626 +/- 42 ng/ml) than in controls (551 +/- 60, p = 0.09). CONCLUSIONS: ICAM-1 and VCAM-1 levels are increased both in patients with CAD and with syndrome X compared with control individuals. These findings may suggest the presence of chronic inflammation with involvement of the endothelium in patients with anginal chest pain and normal coronary angiograms.     

Plasma beta-endorphin levels in silent myocardial ischemia induced by exercise

Although silent myocardial ischemia is a well recognized phenomenon, the reasons for the lack of symptoms in patients with coronary artery disease (CAD) is unclear. Because the endogenous opioid beta-endorphin has been related to pain modulation, plasma beta-endorphin levels were studied before, during and after exercise-induced ischemia in symptomatic and asymptomatic men. Because beta-endorphin responses have been closely linked to adrenocorticotropic hormone (ACTH) and cortisol responses, these hormones also were measured. Nine symptomatic and 12 asymptomatic patients with a high probability (at least 95%) of CAD and 8 apparently healthy men completed a Bruce protocol treadmill test. Blood samples were drawn before, during and 10 minutes after exercise. During exercise the measured hormones showed no significant increases from basal levels. However, plasma beta-endorphin, ACTH and cortisol levels were significantly elevated (p less than or equal to 0.01) 10 minutes after exercise in all 3 groups. There was no significant difference in plasma beta-endorphin levels during or after exercise between the symptomatic and asymptomatic patients with CAD. Thus, differences in circulating levels of beta-endorphin, ACTH and cortisol are not associated with the presence or absence of pain during exercise-induced myocardial ischemia.     

An Evaluation of Levalbuterol HFA in the Prevention of Exercise-Induced Bronchospasm

Background. Exercise-induced bronchospasm (EIB) affects up to 90% of all patients with asthma. Objective. This study evaluated the ability of levalbuterol hydrofluoroalkane (HFA) 90 μg (two actuations of 45 μg) administered via metered dose inhaler (MDI) to protect against EIB in mild-to-moderate asthmatics. Methods. This was a randomized, double-blind, placebo-controlled, two-way cross-over study. Patients with asthma (n = 15) were ≥18 years, had a ≥6-month history of EIB, ≥ 70% baseline predicted forced expiratory volume in 1 second (FEV₁), and a 20% to 50% decrease in FEV₁ after treadmill exercise challenge using single-blind placebo MDI. Levalbuterol or placebo was self-administered 30 minutes before exercise. Treatment sequences were separated by a 3-to 7-day washout period. Spirometry was performed predose, 20 minutes postdose/pre-exercise, and 5, 10, 15, 30, and 60 minutes post-exercise. The primary endpoint was the maximum percent decrease in FEV₁ from baseline (postdose/pre-exercise). The percentage of protected (≤ 20% decrease in post-exercise FEV₁) patients was also assessed. Results. Levalbuterol had significantly smaller maximum percent post-exercise decrease in FEV₁ compared with placebo (LS mean ± SE; ?4.8% ± 2.8% versus ?22.5% ± 2.8%, respectively). For levalbuterol, 14/15 (93.3%) patients had < 20% decrease in post-exercise FEV₁ compared with 8/15 (53.3%) for placebo (p = 0.0143). Treatment was well tolerated. Conclusion. Levalbuterol HFA MDI (90 μg) administered 30 minutes before exercise was significantly more effective than placebo in protecting against EIB after a single exercise challenge and was well tolerated. Clinical Implications. Levalbuterol HFA MDI when administered before exercise was effective in protecting adults with asthma from EIB.     

The association of acute exercise-induced ischaemia with systemic vasodilator function in patients with peripheral arterial disease

Patients with peripheral arterial disease (PAD) frequently experience ischaemic attacks of the affected tissues during exercise. The present study assesses the association of transient exercise-induced leg ischaemia with vasodilator function of the clinically unaffected brachial artery over the course of 4 hours. Thirty male patients with symptomatic PAD and 14 age- and sex-matched healthy controls were included in the study. They performed a treadmill exercise until intolerable exercise-induced ischaemic pain occurred in the affected lower extremity, or for at most 10 min. Flow-mediated dilation (FMD) of the brachial artery was measured at baseline, 30 minutes, 2 hours and 4 hours after exercise. Baseline FMD values were significantly diminished in patients (7.03 +/- 1.99% vs 8.22 +/- 1.60% in controls, p = 0.009). A significant decrease in FMD was observed in patients after exercise (at 30 minutes: 3.92 +/- 1.78% vs 7.03 +/- 1.99% at baseline, p < 0.001; at 2 hours: 6.36 +/- 2.12% vs 7.03 +/- 1.99% at baseline, p = 0.005), followed by a gradual return to its baseline value, whereas FMD in controls non-significantly increased after exercise. The difference in the pattern of FMD change over time between patients and controls was significant (p < 0.001). This study shows that in PAD patients ischaemia during intermittent claudication is related to a transitory functional deterioration of the distant arteries. This indicates the harmful systemic effects of repeated ischaemic attacks during exercise and might explain the generalized and advanced nature of atherosclerotic disease in PAD patients.