Immediate exercise testing to evaluate low-risk patients presenting to the emergency department with chest pain

OBJECTIVES: The aim of this study was to determine whether nicotine, a constituent of cigarette smoke, contributes to acute endothelial dysfunction after smoking one cigarette. BACKGROUND: Animal studies suggest that nicotine might cause an impairment of endothelium-dependent vasodilation via an increase in oxidative stress. METHODS: Sixteen healthy smokers were entered into a randomized, observer-blinded crossover study comparing the effects of nicotine nasal spray (1-mg nicotine) and cigarette smoke (1-mg nicotine, 12 mg tar) on vascular reactivity in the brachial artery. Using high-resolution ultrasound, flow-mediated dilation (FMD) and endothelium-independent, nitroglycerin-induced dilation were assessed at baseline and 20 min after the administration of nicotine (spray or cigarette). RESULTS: In response to similar increases in nicotine serum levels, FMD values declined from 10.2 +/- 4.4% to 6.7 +/- 4.0% after the spray (mean difference: -3.6 +/- 2.0%, 95% confidence interval: -4.6; -2.5, p < 0.0001) and from 9.4 +/- 3.8% to 4.3 +/- 2.8% after the cigarette (-5.1 +/- 2.6%, -6.5; -3.7, p < 0.0001). Nitroglycerin-induced dilation remained similar within both periods. Performing a period effect analysis of variance, a significant influence on FMD was found for the mode of administration (p = 0.017) and the baseline value (p = 0.021). The effect on FMD was more pronounced after the cigarette than after the spray (estimated average effect difference: 1.9% FMD). Oxidation parameters did not increase significantly after nicotine spray or tobacco exposure. CONCLUSIONS: These results demonstrate that nicotine alone causes acute endothelial dysfunction, although to a lesser extent than smoking a cigarette of the same nicotine yield. However, the precise mechanisms by which nicotine leads to this altered vascular reactivity remain unclear.     

Smoking mentholated cigarettes impairs coronary microvascular function as severely as does smoking regular cigarettes

OBJECTIVE: Smoking mentholated cigarettes inhibits the metabolism of nicotine and increases systemic exposure to cigarette smoke toxins. However, the possible effects of smoking mentholated cigarettes on coronary microvascular functions are unknown. We sought to investigate whether smoking mentholated cigarettes impairs coronary flow reserve (CFR) more so than smoking regular cigarettes. METHODS: Twenty otherwise healthy smokers of regular cigarettes (6 women, 14 men; mean age, 25.6 +/- 6.4 years) and 22 non-smoking control subjects were included in the study. To compare the acute effects of mentholated (0.9 mg nicotine, 11 mg tar, 12 mg carbon monoxide) and regular (0.9 mg nicotine, 12 mg tar, 12 mg carbon monoxide) cigarettes on CFR, all subjects underwent an echocardiographic examination that included CFR measurements at baseline. Twenty to 30 minutes after subjects had smoked 2 regular cigarettes and 2 mentholated cigarettes, CFR was again measured in subjects in the smoking group. RESULTS: In response to smoking 2 regular and 2 mentholated cigarettes, CFR values declined from 2.56 +/- 0.60 to 2.06 +/- 0.38 (P < 0.004) and from 2.56 +/- 0.60 to 2.14 +/- 0.30 (P < 0.005), respectively. Smoking mentholated and regular cigarettes impaired CFR to the same degree (P = 0.547). CONCLUSIONS: When compared with smoking regular cigarettes, smoking mentholated cigarettes has similar acute detrimental effects on coronary microvascular functions.     

Arterial blood nicotine concentration and coronary vasoconstrictive effect of low-nicotine cigarette smoking.

Low-nicotine cigarettes have been advertised to the public as less harmful to the cardiovascular system. We studied the effects of smoking two low-nicotine cigarettes on arterial and venous blood nicotine levels, hemodynamics, and coronary vascular tone in 12 patients referred for diagnostic coronary arteriography. All were chronic smokers as evidenced by their elevated baseline arterial and venous cotinine blood levels (139 +/- 30 ng/ml and 155 +/- 34 ng/ml, respectively). High-resolution coronary angiograms were evaluated "blindly" before and after smoking. An electronic caliper was used to measure the diameter of disease-free coronary segments of the left anterior descending and circumflex arteries. Arterial nicotine levels rose from 5 +/- 1 ng/ml at baseline to 37 +/- 7 ng/ml (p less than 0.01) after the first cigarette was smoked and to 45 +/- 8 ng/ml (p less than 0.01) after the second cigarette. Venous nicotine levels rose from 8 +/- 2 ng at baseline to 15 +/- 3 ng/ml (p less than 0.05) after the first cigarette and to 20 +/- 3 ng/ml (p less than 0.01) after the second cigarette. After the first cigarette heart rate increased 8 +/- 2 beats/min (p less than 0.003) and double product 1229 +/- 400 beats/min x mm Hg (p less than 0.02). Compared to baseline values, after the second cigarette heart rate increased 9 +/- 1 beats/min (p less than 0.001) and double product 1767 +/- 486 beats/min x mm Hg (p less than 0.01). Systolic, diastolic, and mean blood pressure did not change significantly after either the first or second cigarette.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects immediate to the inhalation of tobacco smoke with different concentrations of nicotine

Fifteen healthy and non smoking men, age range 20 to 27 years (23.6 +/- 2.5 (SD) were subject of a double blind study designed to compare the immediate cardiovascular effects of smoking "regular" and "light" cigarettes (nicotine content: 1.1 mg and 0.6 mg, respectively). The measured cardiovascular parameters were: heart rate, blood pressure, echographic calculations of the left ventricle fractional shortening, amplitude of the posterior wall systolic movement and posterior wall contraction velocity, as well as QTc interval and T wave amplitude. All those measurements were obtained before and after smoking one or two other kind of cigarette. When the changes evoked by the regular cigarette were compared to the changes evoked by the light cigarette, no significant difference was detected. When analyzing the modifications that each kind of cigarette produced to its respective basal-control measurement the following observations were detected: heart rate increased after smoking both types of cigarette (p less than 0.001), blood pressure was raised only with regular cigarette (systolic, p less than 0.002; diastolic, p less than 0.005). QTc interval was prolonged (p less than 0.05) and T wave amplitude decreased (p less than 0.02) after regular and light cigarette. It is concluded that tobacco of regular and light cigarettes significantly and immediately affects diverse cardiovascular parameters, but there is no a clear or definite difference when the changes produced by the two types of cigarette are compared to each other, at least at the level of nicotine here utilized.     

Acute hemodynamic effect of cigarette smoking and its relationship with nicotine content

We studied the acute effects of cigarette smoking on the cardiovascular system, especially regarding nicotine-related hemodynamic effects using cigarettes with low and high nicotine contents. 40 healthy men who were habitual smokers were divided into two groups: 20 subjects smoked cigarettes of low nicotine content [0.4 mg/cigarette; group 1 (G1)] and another 20 tested cigarettes containing high nicotine [2 mg/cigarette; group 2 (G2)]. All of the subjects were requested to abstain from cigarette smoking for at least 12 hours prior to study, and to rest in the supine position for 30 minutes just prior to the test. They smoked two consecutive cigarettes for 10 minutes, inhaling every 30 seconds by drawing on the cigarette for two seconds, and holding the smoke for three seconds before exhaling. Blood pressure (BP), heart rate (HR) and cardiac output (CO) were measured and blood samples were taken before, and 5, 10 and 30 minutes after the start of smoking. Smoking with a high nicotine content (G2) produced a significant increase in both systolic and diastolic BP (124 +/- 14/78 +/- 8----138 +/- 21/90 +/- 10 mm Hg), but no significant changes in BP were observed in the low nicotine group. HR and CO increased predominantly in both groups (HR: G1; 62 +/- 7----66 +/- 7, G2; 64 +/- 7----76 +/- 9/min, CO: G1; 4.85 +/- 1.36----5.31 +/- 1.37, G2; 4.95 +/- 1.58----5.63 +/- 2.01 l/min), but the present increases were significantly less in G1 than in G2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute effects of cigarette smoking on platelet-dependent thrombin generation.

AIMS: Thrombin is an important factor in the pathogenesis of thrombotic diseases. To clarify whether smoking has an effect in platelet-dependent thrombogenesis, we studied the acute effects of smoking on platelet-dependent thrombin level in smokers. METHODS AND RESULTS: Subjects consisted of ten smokers and nine non-smokers. Platelet-dependent thrombin level measured after overnight fasting was greater in smokers than in non-smokers (smokers vs non-smokers, 121 +/- 47 vs 56 +/- 5 mIU. ml(-1), P < 0.01). When subjects in the smokers group smoked two cigarettes containing 0.9 mg of nicotine per cigarette, platelet-dependent thrombin levels showed a transient three-fold increase in blood samples obtained immediately after smoking (365+/-76 mIU. ml(-1), P < 0.001). Thrombin levels in the blood samples obtained 10 min and 30 min after smoking were less than that in the samples obtained immediately after smoking ceased, but were not significantly different from those in the samples obtained before smoking. Blood nicotine level increased significantly immediately after smoking (P < 0.001), and plasma protein C activity decreased significantly 30 min after smoking (P < 0.05). When nicotine or cotinine was added to the platelet-rich plasma of non-smokers ex vivo, the platelet-dependent thrombin level increased significantly (P < 0.002). CONCLUSION: Platelet-dependent thrombin level is enhanced in smokers, even when not smoking, when compared with non-smokers and increases immediately after smoking. Increases in nicotine and cotinine levels caused by smoking induced a prothrombotic state in smokers via increased platelet-dependent thrombogenesis.     

Effects of vitamin E on chronic and acute endothelial dysfunction in smokers

OBJECTIVES: The aims of this study were to determine whether chronic or acute impairment of flow mediated vasodilation (FMD) in the brachial artery of smokers can be restored or preserved by the antioxidant vitamin E. BACKGROUND: Transient impairment of endothelial function after heavy cigarette smoking and chronic endothelial dysfunction in smokers result at least in part from increased oxidative stress. METHODS: We studied 22 healthy male smokers (mean +/- SD, 23 +/- 9 cigarettes per day) randomly assigned to receive either 600 IU vitamin E per day (n = 11, age 28 +/- 6 years) or placebo (n = 11, age 27 +/- 6 years) for four weeks and 11 age-matched healthy male nonsmokers. Flow mediated vasodilation and endothelium-independent, nitroglycerin-induced dilation were assessed in the brachial artery using high resolution ultrasound (7.5 MHz) at baseline and after therapy. Subjects stopped smoking 2 h before the ultrasound examinations. At the end of the treatment period, a third scan was obtained 20 min after smoking a cigarette (0.6 mg nicotine, 7 mg tar) to estimate transient impairment of FMD. RESULTS: Flow mediated vasodilation at baseline was abnormal in the vitamin E (5.3 +/- 3.8, p < 0.01) and in the placebo group (6.4 +/- 3.5, p < 0.05) compared with nonsmoking controls (11.6 +/- 4.7). Using a two-way repeated measures analysis of variance (ANOVA) to examine the effects of vitamin E on FMD, we found no effect for the grouping factor (p = 0.5834) in the ANOVA over time but a highly significant difference with respect to time (p = 0.0065). The interaction of the time factor and the grouping factor also proved to be significant (p = 0.0318). Flow mediated vasodilation values remained similar after treatment for four weeks in both groups but declined faster after smoking a cigarette in subjects taking placebo compared with those receiving vitamin E (p values from successive differences for the time/group factor: 0.0001/0.0017). The transient attenuation of FMD (calculated as the percent change in FMD) was related to the improvement of the antioxidant status, estimated as percent changes in thiobarbituric acid-reactive substances (r = -0.67, p = 0.0024). Nitroglycerin-induced dilation did not differ between study groups at baseline or after therapy. CONCLUSIONS: These results demonstrate that oral supplementation of vitamin E can attenuate transient impairment of endothelial function after heavy smoking due to an improvement of the oxidative status but cannot restore chronic endothelial dysfunction within four weeks in healthy male smokers.     

Effects of levels of cigarette smoke exposure on symptom-limited spiroergometry

Previous investigations demonstrated reduced exposure to selected cigarette smoke constituents in adult smokers switching from conventional cigarettes (CC) to an electrically heated cigarette smoking system (EHCSS). This study investigated whether reduced exposure and no smoking (NS) would improve exercise performance. In a 3-period crossover study, 18 male adult smokers (age, 43.6+/-5.3 years) of CC were randomized to smoke CC (tar, 11 mg; nicotine, 0.8 mg; carbon monoxide, 11 mg), to use EHCSS (tar, 3 mg; nicotine, 0.2 mg; carbon monoxide, 0.4 mg [Federal Trade Commission method]), or to NS for 3 days before performing symptom-limited spiroergometry. NS and EHCSS vs CC resulted in less severe dyspnea (NS, 44.4% [P<.01 vs CC;] EHCSS, 50% [P=.03 vs CC;] CC, 88.9%), higher working capacity (NS, 2.92+/-0.4 W/kg [P=.06 vs CC;] ECHSS, 2.92+/-0.4 W/kg [P=.04 vs CC;] CC, 2.86+/-0.5 W/kg), higher peak oxygen uptake (NS, 2694+/-466 mL O(2)/min [P=.08 vs CC;] EHCSS, 2830+/-606 mL O(2)/min [P=.03 vs CC;] CC, 2682+/-492 mL O(2)/min), higher anaerobic threshold (NS, 1324+/-306 mL O(2)/min; EHCSS, 1396+/-312 mL O(2)/min [P=.03 vs CC;] CC, 1315+/-290 mL O(2)/min), and higher maximum rate-pressure product (NS, 30.1+/-2.7 x 10(3) mm Hg/min; EHCSS, 2.8 x 10(3) mm Hg/min [P<.01 vs CC;] CC, 30.7+/-29.2+/-3.6 x 10(3) mm Hg/min) indicating that reduced exposure from tobacco smoke and NS for 3 days may improve cardiovascular function as detected by symptom-limited spiroergometry.     

Bacterial endotoxin is an active component of cigarette smoke

BACKGROUND: Chronic bronchitis in cigarette smokers shares many clinical and histologic features with environmental lung diseases attributed to bacterial endotoxin (lipopolysaccharide [LPS]) inhalation. Experimental LPS inhalation mimics many of the acute effects of cigarette smoke in the lower airway. Therefore, we reasoned that LPS may be a biologically active component of cigarette smoke. DESIGN: The Limulus amebocyte lysate (LAL) assay was used to measure LPS in the tobacco and filter tip components of unsmoked 1R4F experimental cigarettes and commercially available "light" cigarettes, as well as in mainstream (MS) and sidestream (SS) smoke particles generated with an automated smoking machine and collected on ventilator mainflow filters. SETTING AND PARTICIPANTS: Blood LPS activity and plasma cytokine concentrations were measured in groups of healthy smokers and nonsmokers who reported to the walk-in clinic at the Baltimore VA Medical Center for unrelated complaints. MEASUREMENTS: Blood LPS levels were measured by LAL assay and plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), soluble TNF receptors I and II (sTNFR I and sTNFR II) were measured by enzyme-linked immunosorbent assay. RESULTS: Bioactive LPS was detected in both the tobacco portion (1R4F, 17.8+/-1.0 microg/cigarette; light, 26.8+/-7.3 microg/cigarette [mean+/-SE]) and filter tips (1R4F, 0.67+/-0.55 microg/cigarette; light, 0.70+/-0.39 microg/cigarette) of cigarettes. Bioactive LPS was also detected in both MS (1R4F, 120+/-64 ng/cigarette; light: 45.3+/-16 ng/cigarette) and SS smoke (1R4F, 18+/-1.5 ng/cigarette; light: 75+/-49 ng/cigarette). Although systemic absorption of inhaled LPS may occur, we failed to detect any differences between nonsmokers and smokers in median blood LPS levels (median values, 66.75 and 72.1 pg/mL, respectively; p = 0.55) or plasma concentrations of TNF-alpha (0 vs 0 pg/mL, respectively; p = 0.71), sTNFR I(1,469 vs 1,576 pg/mL, respectively), sTNFR II (2,011 vs 3,110 pg/mL, respectively), or IL-6 (8.8 vs 0 pg/mL, respectively; p = 0.20). CONCLUSIONS: Smoking one pack of cigarettes per day delivers a dose of respirable LPS that is comparable to the levels of LPS associated with adverse health effects in cotton textile workers. Thus, we suggest that the bioactive LPS in cigarette smoke may contribute to the pathogenesis of chronic bronchitis that develops in susceptible cigarette smokers.     

Effect of acute cigarette smoking, alone or with alcohol, on gastric barrier function in healthy volunteers

BACKGROUND: Smoking is a risk factor for gastroduodenal ulcer and gastric adenocarcinoma. However, the pathophysiological mechanisms induced by acute cigarette smoking in the human gastric mucosa are poorly understood. AIM: To evaluate the effect of acute cigarette smoking, alone or with alcohol, on the gastric permeability to sucrose, a specific marker of mucosal damage in the stomach. SUBJECTS AND METHODS: Twenty healthy volunteers (8 smokers/12 non-smokers) were studied. Each fasted subject ingested 500 ml of a 20% sucrose solution and the amount of sucrose excreted in a 5-hour urine collection was measured by gas chromatography Four sucrose permeability tests were carried out: 1. basal, 2. while smoking 5 cigarettes, 3. after drinking 50 ml of a 40 degrees alcoholic beverage, 4. a combination of 2+3. RESULTS: Sucrose excretion increased after alcohol ingestion (40.5 +/- 6.0 mg vs 143.1 +/- 28.9 mg, p = 0.002), but was not modified by acute cigarette smoking (34.4 +/- 5.9 mg). When alcohol and cigarettes were simultaneously consumed, the increase in alcohol-induced sucrose excretion was significantly reduced (73.1 +/- 16.6 mg, p = 0.03). Basal sucrose excretion was similar in smokers and non-smokers. However, in acute cigarette smoking, a decrease in sucrose excretion was observed in smokers (p = 0.02) but not in non-smokers. CONCLUSIONS: These results indicate that acute cigarette smoking may tighten the gastric mucosa in habitual smokers and this is associated with a smaller increase of gastric permeability induced by alcohol.     

Stress modulation over the day in cigarette smokers

This review summarizes the findings from a series of four published studies into the relationship between cigarette smoking and stress. In each study, feelings of anxiety/stress were significantly lower post-smoking than pre-smoking (p < 0.001). However, while moods improved immediately after smoking, mood impairments occurred between cigarettes. This repetitive cycle of mood reversals provides a clear rationale for repetitive/addictive cigarette use. The degree of stress modulation was significantly related to the sedative subscale of the Smoking Motivation Questionnaire (p < 0.01). However, high SMQ sedative subjects reported above-average stress prior to smoking, rather than below-average stress after smoking. Thus stress modulation represented mainly the relief of adverse moods, rather than the attainment of beneficial moods. Deprived smokers reported a diurnal pattern of increasing stress, confirming the deleterious effects of nicotine deprivation. These studies demonstrated the importance of mood control as a motive for smoking. They indicate that smokers gain little real advantage from cigarettes, but smoke mainly to for stall nicotine depletion. The deleterious mood effects of acute nicotine withdrawal oho helps explain why, when smokers quit smoking, they experience reduced levels of daily stress.     

Ethnic differences in arterial stiffness and wave reflections after cigarette smoking

BACKGROUND: Smoking increases plasma nicotine. Nicotine releases catecholamines and alters arterial distensibility. The nicotine intake per cigarette is greater and serum cotinine levels, the proximate metabolite of nicotine, are higher in Blacks than in Whites. We tested the hypothesis that cigarette smoking increases the pulse wave velocity (PWV), a marker of arterial stiffness, and the augmentation index (AI), a measure of wave reflection, more in Blacks than in Whites. METHODS: We matched Black (n = 30) and White (n = 30) smokers for age, gender, body mass index and height. We determined carotid-femoral PWV (PWVCF) and carotid-radial PWV (PWVCR) (Complior), the AI derived from the aortic pressure waveform (applanation tonometry, Sphygmocor), blood pressure, heart rate (HR) and cotinine levels before and after cigarette smoking. We also performed measurements in 16 participants after sham smoking. RESULTS: Smoking increased the AI, PWVCF and PWVCR in the whole population (all P < 0.05, n = 60). Increases in the AI and PWV were positively related to serum cotinine levels (all P < 0.05). Smoking increased serum cotinine (P = 0.01) and mean blood pressure (P = 0.03) more, but raised the HR to a lesser extent, in Blacks [+8 +/- 4 versus +13 +/- 6 beats/min in Whites (mean +/- SD), P = 0.01]. Blacks disclosed larger increases in AI adjusted for HR (Blacks, +7.2 +/- 8 versus Whites, +4.4 +/- 8%; P = 0.03), PWVCF (Blacks, +1.1 +/- 0.2 versus Whites, +0.6 +/- 0.3 m/s; P < 0.01) and PWVCR (Blacks, +1.4 +/- 0.1 versus Whites, +0.7 +/- 0.4 m/s; P < 0.01) normalized for the mean blood pressure. No changes were observed with sham smoking. CONCLUSIONS: Smoking acutely increases the PWV and AI in Blacks more than in Whites. Differences in nicotine metabolism and beta-adrenergic sensitivity could explain these findings.     

Time course of some effects of cigarette smoking on platelets.

Eight male habitual smokers smoked two cigarettes over a 20-min period following a 12-h period of abstinence. Antecubital venipuncture was performed immediately before, immediately after, and 55 min and 2 h after smoking had ceased. At these times, the mean values (+/- SD) of collagen-induced platelet aggregation were 45 +/- 5, 68 +/- 5, 59 +/- 6 and 52 +/- 5 chart units, respectively, while the corresponding values for the mean platelet aggregate ratio were 0.91 +/- 0.01, 0.82 +/- 0.03, 0.87 +/- 0.02 and 0.90 +/- 0.02, respectively. Mean collagen-induced platelet aggregation was significantly (P less than 0.005) higher immediately after, and 55 min and 2 h after smoking. The mean platelet aggregate ratio was significantly (P less than 0.001) lower immediately after and 55 min after smoking. Correlation coefficients between the concentration of nicotine in each of the 24 plasma samples obtained after smoking and the corresponding values of collagen-induced platelet aggregation and the platelet aggregate ratio were 0.41 (P less than 0.05) and -0.50 (P less than 0.02), respectively. It is concluded that when habitual smokers abstain from smoking overnight, a 20-min period of cigarette smoking may enhance platelet aggregability for as long as 2 h.     

Profound vasoconstrictive effect of cigarette smoking in diabetics with autonomic neuropathy.

Changes in leg skin temperature during and after cigarette smoking were examined in 25 diabetics with autonomic neuropathy (au-neuropathy) (mean age 52 +/- 2 years) and 23 without (mean age 49 +/- 2 years), and 15 normal controls (mean age 49 +/- 2 years) using a Thermoviewer JTG 3300. All subjects were habitual smokers. Japanese Seven Star cigarettes (each containing 1.2 mg nicotine) were used for the test. Tender brand cigarettes (0.3 mg) were used additionally to compare the effect of nicotine content on the results. The smoking-stimulated thermographic pattern in the control group was rather flat, with a slight decrease in temperature followed by a slight increase before returning to the baseline level 15-20 min after smoking. The frequency of the typical temperature decreasing pattern, characterized by a profound decrease and gradual return to the baseline level in about 1 h, was significantly higher in the diabetic group than in the control group (33/48 vs 1/15; P less than 0.005). A comparison of the two diabetic subgroups revealed that the frequency was considerably higher in the subgroup with au-neuropathy (23/25 vs 10/23). These results suggest that au-neuropathy affects smoking-induced vasoconstriction in diabetic subjects. The maximum temperature decreases recorded were 1.5 +/- 2.0 and 2.69 +/- 0.24 degrees C in the controls and diabetics with au-neuropathy, respectively. The effect of Tender cigarettes with a low nicotine content was much weaker than that of Seven Star, which further suggests that smoking-induced vasoconstriction was also nicotine-dependent.     

Doppler ultrasound evaluation of acute effects of cigarette smoking on portal blood flow in man

The acute systemic haemodynamic effects of cigarette smoking are well known, but there are no studies dealing with the possible smoke-related acute changes of splanchnic circulation in man. In the present study we evaluated the acute effects of cigarette smoking on portal blood flow (PBF) in normal subjects by the use of Doppler ultrasound. Twenty-three normal volunteers were asked to smoke two cigarettes with a known total nicotine content (1.1 mg each) in a supine position. Each cigarette was smoked during a 5 min period and a 5 min interval between the two cigarettes was allowed. Both mean PBF velocity and volume were evaluated at time 0 (basal values) and 8, 15, 30, 45 and 60 min after the first inhalation of the first cigarette. The basal mean PBF velocity (22 cm/s; 95% CI 20.9–24.2) was significantly decreased at 8 min (19 cm/s; 95% CI 17.9–20.8; P< 0.0007) and 15 min (20 cm/s; 95% CI 17.8–21.3; P< 0.005). Similarly, the PBF volumes at 8 min (710 mL/min; 95% CI 660–876; P< 0.002) and 15 min (750 mL/min; 95% CI 650–862; P< 0.005) were significantly lower than those measured at time 0 (850 mL/min; 95% CI 766–987). Both mean PBF velocity and volume measured at successive times did not differ significantly from basal values. The present study shows that cigarette smoking causes acute and transient reduction of PBF velocity and volume in normal subjects.     

Association between cigarette smoking and hypoxanthine guanine phosphoribosyltransferase activity

The aim of this study was to investigate the association between smoking behavior and hypoxanthine guanine phosphoribosyltransferase (HGPRT) activity. A cross-sectional study was performed of 82 men, including 38 non-smokers and 44 smokers. Inosine monophosphate (IMP), the product of HGPRT (used as the index of activity), was measured in peripheral blood mononuclear cells using high-performance liquid chromatography. The factors potentially associated with HGPRT activity included age, glutamyl oxaloacetic transaminase, glutamyl pyruvic transaminase, cholesterol, uric acid, triglycerides, creatinine, body mass index, gout, systolic blood pressure, diastolic blood pressure, alcohol consumption, and cigarette smoking. Mean HGPRT activity was 7.05 +/- 3.44 nmol/10(6) viable cells/hour for all participants, and was significantly lower for smokers than for non-smokers (6.24 +/- 3.40 vs 7.98 +/- 3.28 nmol/10(6) viable cells/hour; p = 0.02). In addition, as the number of smoked cigarettes increased, the HGPRT activity decreased (p < 0.05). The age at onset of cigarette smoking showed a positive correlation with HGPRT activity after adjusting for smoking duration, serum uric acid, and cigarettes smoked per year using a multiple regression model (p < 0.001). We concluded that the greater the number of cigarettes smoked, the lower the HGPRT activity, and that HGPRT activity was higher in smokers who had started smoking later.     

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.     

Carbon monoxide, nicotine and the 'safer' cigarette

15 healthy adults (5 women, 10 men) have been exposed to each of four experimental conditions: rebreathing of air or carbon monoxide, and the smoking of two low-nicotine (0.3 mg) or medium-nicotine (1.2 mg) cigarettes. The dose of carbon monoxide selected (80 ml) had no effect on resting heart rate or electrocardiogram, nor did it modify the exercise heart rate, ventilation, oxygen consumption or electrocardiogram. Both types of cigarette produced variable changes in the blood carboxyhaemoglobin level, increments being greatest in heavy smokers, and least in former smokers, pipe and cigar smokers, Gains of carboxyhaemoglobin were less with low-nicotine than with medium-nicotine cigarettes. Both types of cigarette produced some increase of resting heart rate, but the smoking of two cigarettes was insufficient to modify the exercise heart rate, ventilation, or oxygen consumption. The electrocardiogram also showed no signs of ischaemia during either rest or effort. It is suggested that, for the light and moderate smoke, the 'safest' cigarette may be one with a low tar and a very low nicotine yield. On the present data, this would also induce only small increments of blood carboxyhaemoglobin levels.     

Respiratory symptom relief related to reduction in cigarette use

INTRODUCTION: Many smokers reduce their cigarette consumption during failed attempts to quit. We report the impact of changes in consumption on smoking-related respiratory symptom severity (SRRSS). METHODS: Between February 2002 and May 2004 we recruited 383 smokers from 5 methadone maintenance programs for a randomized trial of nicotine replacement plus behavioral treatment versus nicotine replacement alone for smoking cessation. Cigarette use in the 28 days prior to the interview, and severity of SRRSS using a 7-item respiratory index, were assessed at baseline and at 3-month follow-up. OUTCOME: Baseline minus 3-month assessment difference in SRRSS score. RESULTS: Follow-up of 319 participants (83.3%), mean age 40.4 years, 51.4% male, who smoked 26.4 cigarettes per day, demonstrated a mean reduction of 16.7 cigarettes per day. A reduction in cigarette use was positively and significantly (b=0.29, t=5.16, P<.001) associated with a reduction in smoking-related symptom severity after adjusting for age, gender, race, years of regular smoking, baseline nicotine dependence, and history of treatment for asthma or emphysema. A 1 standard deviation reduction in average daily smoking (about 14.1 cigarettes) was associated with a 0.28 standard deviation decrease in smoking-related symptom severity. CONCLUSION: Reduction in symptom severity increases as absolute reduction in daily smoking increases. This is the first study to demonstrate an association between subjective short-term health changes and reduction in smoking.     

The influence of cigarette smoke on metabolism of eicosanoids in rat lung in terms of variation of 15-hydroxyeicosatetraenoic acid and 11-dehydrothromboxane B2

We investigated the effects of cigarette smoking on metabolism of two eicosanoids, 15-hydroxyeicosatetraenoic acid (15-HETE) and 11-dehydrothromboxane B2 (11-dehydro-TXB2) in the lung. Twelve female Wistar rats aged between 5 and 6 weeks were chosen and the smoking group (SG, n = 6) was compared to the control group (CG, n = 6). Cigarette smoke exposure was performed using a Hamburg-II inhalation apparatus and the dose was 10 cigarettes in 30 min. Bronchoalveolar lavage (BAL) was conducted 30 min after smoking exposure and the recovered BAL fluid was centrifuged at 3000 rpm for 10 min. The levels of 15-HETE and 11-dehydro-TXB2 of the supernatant were measured by radioimmunoassay in each sample. Recovered 15-HETE significantly increased in SG (SG: 490 +/- 109 pg, CG: 191 +/- 63 pg, p less than 0.05), while there was no significant difference in recovered protein (SG: 2.64 +/- 0.50 mg, CG: 2.23 +/- 0.10 mg), 11-dehydro-TXB2 (SG: 128 +/- 13 pg, CG: 156 +/- 7 pg). We conclude that acute cigarette smoke exposure increases recovered BAL fluid 15-HETE, a potent inflammatory mediator and that 15-HETE in BAL fluid may indicate lung injury induced by smoking.