Effect of cilostazol on impaired vasodilatory response of the brachial artery to ischemia in smokers

The vascular endothelial function of smokers is known to be impaired. This study investigated whether cilostazol could improve the vasodilatory response of the brachial artery to ischemia, an indicator of endothelial function, in ten male smokers. Endothelium-dependent vasodilatation and endothelium-independent vasodilatation of the brachial artery were measured in 11 male non-smokers and 20 male smokers with matching age and weight. The results showed that the vasodilatory response to reactive hyperemia was significantly smaller in the smokers (4.8 +/- 1.6%) when compared to that in the non-smokers (7.6 +/- 2.5%) (p = 0.0013). However, no significant difference in the vasodilatory response to isosorbide dinitrate was observed between the two groups. In addition, there were no significant differences in serum lipid, Lp (a), or blood homocysteine between the smokers and non-smokers. When 150 mg/day of cilostazol was administered for two weeks, the vasodilatory response to reactive hyperemia significantly improved (4.2 +/- 1.2% to 7.8 +/- 3.5%, p = 0.0032). The increased vasodilatory response to reactive hyperemia by cilostazol was reduced after cessation of the drug (4.5 +/- 1.5%). These findings suggest that cilostazol improves vascular endothelial dysfunction in smokers.     

Comparison of mortality rates after acute myocardial infarction in smokers versus nonsmokers

Patients who smoke paradoxically have favorable outcomes after acute myocardial infarctions compared with nonsmokers. However, after adjustment for age only, the decrease in all-cause mortality in the smoker population is explained by the smokers' generally younger age, with better prognoses due to their age.     

Examination of the microcirculation damage in smokers versus nonsmokers with vasospastic angina pectoris

Endothelial dysfunction is considered one of the mechanisms underlying vasospastic angina pectoris (VSA). It is also known that smokers have abnormalities in endothelial dysfunction. Although smoking is a major risk factor for coronary artery disease, microvascular abnormalities have not been well shown. We investigated clinical characteristics and coronary reactivity with adenosine triphosphate in smokers with VSA. Twenty-two consecutive patients whose coronary spasm was documented in the left anterior descending (LAD) coronary artery with acetylcholine were enrolled. Coronary blood flow responses were also evaluated by intracoronary Doppler flow velocity recordings in the LAD coronary artery. Average peak velocities (APVs) were measured at baseline and intracoronary administration of adenosine triphosphate (50 microg) in 11 smokers (age 60+/-9 years; 8 men) and 11 nonsmokers (age 61+/-10 years, 5 men). Coronary flow reserve (CFR) was calculated by the ratio of baseline to hyperemic APV. Multivessel spasm was demonstrated in 6 smokers and only 2 nonsmokers (p<0.05). APV at rest in smokers (13.4+/-3.0 cm/s) was similar to that in nonsmokers (13.5+/-2.9 cm/s). However, CFR in smokers (2.6+/-0.7) was significantly lower than in nonsmokers (3.4+/-0.8; p<0.05). In conclusion, multivessel spasm was demonstrated in smokers in clinical settings, and microcirculation damage is prominent in smokers with VSA.     

青年长期吸烟者血管内皮依赖性舒张功能的改变

目的:探讨青年长期吸烟血管内皮依赖性舒张功能的改变。方法:测定20例长期吸烟青年及15例正常对照者血流介导的和硝酸甘油介导的肱动脉内径改变。结果:两组肱动脉内径基础值(3.75±0 61mm:3.81±0.55mm)及硝酸甘油介导的肱动脉舒张[(22.13±7.65)％:(23.45±8.21)％]无显著差异(P>0.05),而血流介导的血管扩张存在显著差异.为[(3.61±2.90)％:(8.32±4.75)％]、P<0.01。单因素相关分析表明,肱动脉内皮依赖件舒张与吸烟量呈显著负相关(r=0.523.P<0.001).结论:青年长期吸烟者血管内皮依赖性舒张功能明显受损,受损程度与吸烟量有关。     

Effect of supplemental phytonutrients on impairment of the flow-mediated brachial artery vasoactivity after a single high-fat meal

OBJECTIVES: Our objective was to determine if long-term daily administration of phytonutrient supplements can prevent the immediate adverse impact of a high-fat meal and increase the production of nitric oxide. BACKGROUND: Ingestion of a high-fat meal impairs flow-mediated vasodilation of the brachial artery for at least 4 h; however, co-ingestion of vitamin antioxidants or a green salad has been shown to prevent this effect. METHODS: Flow-mediated brachial artery reactivity test (BART) both before and 3 h after a 900 calorie 50 g fat meal was evaluated in 38 healthy volunteers (age 36.4 +/- 10.1 years). Subjects were randomized to four weeks of daily supplementation with a powdered fruit vegetable juice concentrate (Juice Plus [JP]) along with a complex supplement providing nutritional antioxidants and various herbal extracts (Vineyard [V]), JP alone, or a matching placebo. At three and four weeks, BART was repeated both before and after the high-fat meal. Serum nitrate/nitrite concentrations were measured at baseline and at four weeks. RESULTS: Four weeks of the JP-V combination blunted the detrimental effect of the high-fat meal (-47.5 +/- 23.4% at baseline vs. -1.7 +/- 9.7% at four weeks [p < 0.05]). Four weeks of JP alone had a similar beneficial effect (-45.1 +/- 19.7% at baseline vs. -16.6 +/- 10.3% at four weeks [p < 0.05]), whereas there was no substantial effect of the placebo. In the subjects treated with supplements, concentrations of serum nitrate/nitrite increased from 78 +/- 39 to 114 +/- 62 microm/l (p < 0.02). CONCLUSIONS: Daily ingestion of modest amounts of a fruit/vegetable juice concentrate with or without adjunctive phytonutrient supplementation can reduce the immediate adverse impact of high-fat meals on flow-mediated vasoactivity and increase nitrate/nitrite blood concentration.     

Hemodynamic factors changing blood flow velocity waveform and profile in normal human brachial artery

We have investigated the influence of changes of perfusion pressure and local peripheral resistance on blood flow velocity waveform and profile in normal human peripheral arteries. Blood flow velocity and profile were recorded from the distal end of the left brachial artery in ten normal subjects by means of an ultrasonic device. The records were obtained in basal conditions and after blood pressure in the brachial artery and local peripheral vascular resistance were changed, separately or together, by progressive inflation of two arm cuffs, one encircling the proximal half of the left arm and the other the middle part of the left forearm. Both blood flow velocity waveform and profile were shown to be markedly modified by changes in perfusion pressure and local peripheral vascular resistance. Reduction of perfusion pressure decreased both forward and reverse peak velocities, but had the largest effect upon reverse velocity. The upslope and the downslope of the forward velocity wave were left unchanged. Increase in local peripheral vascular resistance markedly augmented reverse peak velocity, whether perfusion pressure was normal or reduced. Increased resistance only slightly influenced peak forward velocity.     

Extra-ascending aortic versus intra-descending aortic balloon counterpulsation-effect on coronary artery blood flow

BACKGROUND: Diastolic counterpulsation has been used to provide circulatory augmentation for chronic heart failure or for short-term cardiac support. Recently an extra-aortic balloon (EAB) counterpulsation device has been proposed. AIM: To compare the circulatory effects of counterpulsation using the EAB or an intra-aortic balloon (IAB) in the acute pig model. METHODS: In six anaesthetized great white pigs (paced at 100 bpm), ECG, arterial and central venous pressures, flow in the coronary circulation and descending thoracic aorta were measured. Baseline data was collected, then with the EAB or an IAB fitted using 1:1 and 1:2 counterpulsation modes. Baseline data was compared to EAB and IAB data in 1:1 mode. Assisted beat data compared to unassisted beat data was also analysed in 1:2 mode. RESULTS: Both devices augmented peak diastolic arterial pressure, and decreased afterload. EAB counterpulsation increased diastolic coronary flow in both the 1:1 mode by 69% (p < 0.05) and in the 1:2 mode by 63% (assisted versus unassisted beat, p < 0.05). The IAB significantly increased diastolic coronary flow only in the 1:2 mode by 28% (p < 0.01). Both devices augmented total coronary flow and some augmentation of aortic flow was observed. CONCLUSION: The circulatory effect of the EAB and IAB counterpulsation were comparable. This suggests the EAB could be used as a non-blood contacting heart assist device in patients suffering moderate-severe heart failure.     

Pulsed Doppler: determination of diameter, blood flow velocity, and volumic flow of brachial artery in man

A pulsed Doppler velocimeter suitable for the determination of blood flow velocity and volumic flow in peripheral arteries is described. The apparatus has two main characteristics: an adjustable range-gated time system and a double transducer probe. The error in the determination of the angle between the ultrasound beam and flow of blood with this apparatus was less than 2%, and overestimation of the arterial diameter due to the sample volume size did not exceed 0.035 +/- 0.015 cm. The apparatus was used to determine diameter, blood flow velocity and volumic flow of the brachial artery of 22 healthy men. The values were respectively 0.440 +/- 0.010 cm, 9.15 +/- 1.01 cm.s-1 and 85 +/- 10 cm3.min-1. Administration of intravenous nitroglycerin significantly increased the arterial diameter (p less than 0.001) without any significant change in volumic flow. The described pulsed Doppler velocimeter provides an accurate noninvasive method for determining volumic flow in peripheral arteries in clinical investigation and cardiovascular pharmacology.     

Effect of internal mammary artery mobilization on sternal blood flow

Use of the internal mammary artery as a conduit for coronary artery bypass has enhanced this procedure in terms of prolonged graft patency. An earlier warning that use of both arteries would devascularize the sternum was based on postmortem radiologic imaging. This was complemented by a subsequent animal study employing isotopic microspheres. In the present clinical study, laser Doppler flowmetry was adapted to identify changes in blood supply to the left half of the divided manubrium sternum during separation of the left internal mammary artery from its chest wall attachment. Our finding of continued blood flow after this event suggests that complete devascularization of the sternum does not take place. Quality of sternal bone and surrounding tissues and clinical indications should remain as factors influencing use of one or both internal mammary arteries.     

Urine bactericidal activity of pefloxacin versus norfloxacin in healthy female volunteers after a single 800-mg oral dose

Summary In an open randomised crossover study the antibacterial activity of pefloxacin and norfloxacin was assessed in the urine after a single 800-mg oral dose in 14 healthy female volunteers. Pefloxacin demonstrated lower peak concentrations in the urine than norfloxacin (mean, 217.2 mg/l versus 492.9 mg/l as determined by the microbiological assay) but pefloxacin was present over a longer period of time in sufficient concentrations than norfloxacin. Mean urine levels of at least 2 mg/l were present for 7 days after pefloxacin administration and 2 days after norfloxacin administration as determined by the microbiological assay. Overall, the urinary recovery of pefloxacin and norfloxacin amounted to 49.3% and 25.1%, respectively, of the total administered dose. The average urine bactericidal activity against the five test organisms was as follows: against reference strainEscherichia coli ATCC 25922 susceptible to nalidixic acid (Nal-S) for 5 days with pefloxacin and 2 days with norfloxacin; against three clinical isolates, one strain each ofE. coli resistant to nalidixic acid (Nal-R),Klebsiella pneumoniae Nal-R, andStaphylococcus saprophyticus, for 3 days with pefloxacin and 24 h with norfloxacin; and against a clinical isolate ofEnterococcus faecalis for 2 days with pefloxacin and 12 h with norfloxacin. In conclusion, pefloxacin as a single dose proved to have sufficiently high and long-lasting urine bactericidal activity against urinary pathogens. These findings support the results of a meta-analysis of seven clinical trials in patients with uncomplicated lower UTI, demonstrating a single oral dose of 800 mg pefloxacin to be as effective as a conventional treatment with comparative drugs [21].     

Late systolic wave on brachial artery blood flow velocity pattern in patients with coronary artery disease and its relation to vascular stiffness

Duplex-Doppler study typically exhibits triphasic brachial artery blood flow velocity pattern in subjects classified as normal without clinically evident atherosclerotic complications, heart disease, hypertension, or diabetes mellitus. In this study, the authors described the late systolic wave on the brachial artery blood flow velocity pattern in patients with coronary artery disease and investigated the relation between late systolic wave and vascular stiffness. Blood flow profile and velocity of the brachial artery were determined noninvasively by ultrasound pulsed-Doppler technique under the guidance of a B-mode ultrasound image in 96 patients with coronary artery disease (CAD). The control group consisted of 23 healthy subjects with no or maximally 2 risk factors (only among age, cigarette smoking, obesity, and gender) for vascular disease. None of the patients and controls had clinical evidence of arterial disorders at upper extremities. In 32 patients (33%) with CAD, a late systolic wave was observed in the brachial artery Doppler study. On the other hand, no late systolic wave was observed in the healthy subjects. In addition, multivessel disease, hypertension, advanced age, diabetes, and smoking were significantly more frequent in patients with the late systolic wave. In conclusion, peripheral arterial abnormalities induced by vascular stiffness may produce alterations in regional wave reflections, and the normal triphasic pattern of the brachial artery blood flow may change by the appearance of the late systolic wave.     

Differentiation in the short- and long-term effects of smoking on plasma total ghrelin concentrations between male nonsmokers and habitual smokers

To explore the association between the anorexigenic effects of nicotine and the orexigenic properties of ghrelin, plasma total ghrelin levels were measured in nonsmokers and habitual smokers before and after short-term exposure to cigarette smoke. Thirty-one male smokers and 23 nonsmoking volunteers were matched for age and body mass index. After an overnight fast and abstinence from smoking, they all smoked 2 cigarettes consecutively (same brand, rate of inhalation, and duration of smoking). Total ghrelin concentrations were measured by radioimmunoassay before smoking (baseline), immediately afterward, and 30, 60, and 90 minutes after the second cigarette. Baseline ghrelin levels were not different between smokers and nonsmokers. Smoking did not have an immediate influence on ghrelin concentrations in smokers (analysis of variance for repeated measurements, P=0.74), whereas there was a progressive decline in nonsmokers, reaching statistical significance at 30 minutes (P=.04) and a nadir at 60 minutes (P=.04) after smoking. Moreover, the area under the curve for the changes of ghrelin over time after smoking was lower in nonsmokers than in smokers (-287.2+/-167.1 vs 29.2+/-125.3 ng.min/L, P=.03). In conclusion, fasting plasma total ghrelin concentrations are not different between male smokers and nonsmokers. Smoking does not provoke any short-term change in ghrelin levels in smokers, but induces a decline in nonsmokers. If the anorectic effect of smoking is ghrelin induced, this effect may be present only in people not habituated to smoke exposure. In habitual smokers, ghrelin suppression by short-term smoking could be blunted as a result of desensitization due to prolonged nicotine exposure.     

Measurement of mucociliary clearance in smokers and nonsmokers using a bronchoscopic video-technical method

We used a bronchoscopic video-technical method to measure mucociliary clearance in vivo. 1-mm discs of polyethylene were placed on the tracheal mucosa. Their cephalad movement was recorded on video-tape via a videocamera adapted to the bronchoscope optic, and the mucous transport velocity was estimated. In 10 dogs the reproducibility of this method was demonstrated by measuring the mucociliary clearance twice at an interval of 7 days. Measurements performed in 10 smokers and 7 nonsmokers showed differences between the two groups. In nonsmokers the mean mucous transport velocity cephalad in the trachea was 18.5 mm/min and in smokers 6.8 mm/min. Since each measurement took only a few minutes this method can easily be used in connection with routine bronchoscopy. The advantages and shortcomings of the method are discussed.     

Ultrasonic determination of the common carotid and brachial artery blood flow in patients with acute hepatic failure--with special reference to a decrease in common carotid artery blood flow and its relationship with brain edema

A study was conducted to elucidate characteristics of circulatory parameters in patients with acute hepatic failure (AHF) employing Swan-Ganz catheter method and, in particular, ultrasonic quantitative flow measurement (QFM) system. The following results were obtained: 1) In five AHF patients who received Swan-Ganz catheter examinations, significant increases of cardiac index as well as decreased systemic vessel resistance were observed. 2) QFM in 11 patients with AHF revealed a significant increase of brachial artery blood flow (Br.F.), whereas common carotid blood flow (Ca.F.) was found to be significantly decreased. Thus, ratio of Ca.F./Br.F. showed a marked reduction as compared with that of control patients. 3) Vessel resistances measured by QFM were found to be significantly reduced in brachial artery, whereas markedly elevated in common carotid artery. 4) Those changes of circulatory parameters as described above were found to restore toward normal in parallel with the improvement of clinical features. 5) Vessel resistances of common carotid artery (Ca.R.) of AHF patients showed a significant negative correlation with CT values in the white matter of the brain, being regarded to well represent the degree of brain edema. In addition, in a case of AHF in whom intracranial pressure (ICP) was directly measured, time course of changes in Ca.F. was found to be in "mirror image" with that of ICP. Thus, it is strongly suggested that the increase of Ca.R. may well be induced, at least in part, by the elevated ICP in AHF patients.     

Effect of pregnancy on autoregulation of cerebral blood flow in anterior versus posterior cerebrum

Endothelin receptor antagonists and phosphodiesterase type 5 inhibitors are used to treat pulmonary arterial hypertension. We tested the hypothesis that a selective endothelin type A receptor antagonist (ambrisentan) and a phosphodiesterase type 5 inhibitor (tadalafil) may act synergistically to relax endothelin-constricted pulmonary arteries. Rat isolated intrapulmonary arterial rings contracted with 8 nmol/L endothelin-1 were relaxed by 10 nmol/L ambrisentan and 30 nmol/L tadalafil alone by 26±3% and 21±1%, respectively, whereas both drugs in combination acted synergistically to relax arterial rings by 83±6%. The nonselective endothelin type A and B receptor antagonists bosentan (100 nmol/L) and macitentan (30 nmol/L) alone relaxed endothelin-contracted rings by 30±5% and 24±3%, respectively. Combinations of 30 nmol/L tadalafil with 100 nmol/L bosentan or 30 nmol/L macitentan relaxed endothelin-contracted rings by 53±5% or 46±7%, respectively; these values are similar to the calculated sums of the individual effects of these compounds. Denudation of endothelium from pulmonary arterial rings abolished the vasodilator response to 30 nmol/L tadalafil and the synergistic vasorelaxant effect of tadalafil with ambrisentan. In the presence of 1 μmol/L BQ-788, a selective endothelin type B receptor antagonist, the vasorelaxant effects of 10 nmol/L ambrisentan and 30 nmol/L tadalafil were additive but not synergistic. These data can be interpreted to suggest that ambrisentan and tadalafil synergistically inhibit endothelin-1-induced constriction of rat intrapulmonary arteries and that endothelin type B receptors in endothelium are necessary to enable a synergistic vasorelaxant effect of the drug combination.     

测量踝部动脉血压与肱动脉血压、主动脉内血压的对比研究

目的　探讨下肢血压测量方法。方法　对高血压病组及非高血压病组共 10 7例病人采取将袖带缠于小腿下端监听足背动脉血压 ,并与肱动脉血压、主动脉内血压进行对比研究。结果　两组踝部动脉血压与肱动脉血压呈显著正相关 (P <0 0 0 1) ,两组四肢血压与主动脉内血压相关性检验 ,除高血压组踝部动脉舒张压外均有显著相关性 (P <0 0 5 )。踝部动脉收缩压和舒张压平均比肱动脉分别高 10和 5mmHg;肱动脉收缩压低于主动脉内收缩压 5mmHg ,舒张压约高于主动脉内舒张压 5～ 6mmHg ;踝部动脉收缩压高于主动脉内收缩压 6mmHg ,舒张压约高于主动脉内舒张压 10mmHg。结论　测量踝部动脉血压的方法是可信的 ,但高血压组的踝部动脉舒张压与主动脉内舒张压相关性较差。