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Enhanced peripheral vasodilation in humans after a fatty meal

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第2期36卷 417-422页

作者： Raitakari, OT Lai, N Griffiths, K McCredie, R Sullivan, D Celermajer, DS Royal Prince Alfred Hosp Dept Cardiol Camperdown NSW 2050 Australia Royal Prince Alfred Hosp Dept Clin Biochem Camperdown NSW 2050 Australia Univ Sydney Dept Med Sydney NSW 2006 Australia Turku Univ Cent Hosp Dept Clin Physiol FIN-20520 Turku Finland

OBJECTIVES We sought to study the effects of a fatty meal on vascular reactivity, including endothelial function and maximal vasodilation. BACKGROUND Recent reports regarding the physiological changes in peripheral vasculature after eating a fatty meal have been controversial. METHODS Twelve volunteers were studied before, 3 h after, and 6 h after a high-fat meal (1030 kcal, 61 g fat) rich in saturated fatty acids, and 10 were restudied after a similar meal rich in monounsaturated fatty acids. Endothelial function was assessed as flow-mediated dilatation (FMD) in the brachial artery using ultrasound. Resting and postischemic forearm blood flow (FBF) were recorded using venous occlusion strain-gauge plethysmography, before, and every 10 to 15 s after, 5 min upper arm ischemia. RESULTS Brachial artery basal diameter, resting FBF and postischemic hyperemia increased after high-fat meats (all p < 0.001), whereas FMD did not change. The increase in resting FBF correlated with increases in postprandial insulin (r = 0.80, p < 0.002) and triglyceride (r = 0.77, p < 0.005) levels. CONCLUSIONS We concluded that eating a fatty meal induces vasodilation and increases resting and stimulated FBF and that these observations are probably mediated by postprandial changes in insulin and/or triglyceride levels. The metabolic changes that occur after meals are not associated with impaired endothelial nitric oxide release in the conduit arteries, (C) 2000 by the American College of Cardiology.

关键词：动脉/生理学胆固醇/血液膳食脂肪类/药理学内皮血管/药物作用前臂/血液供给高半胱氨酸/血液充血/病理生理学体积描记术饭后期间/生理学局部血流血管舒张/药物作用青少年成年人女(雌)性人类男(雄)性

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Measurement of total lung deposition of inhaled ultrafine particles in healthy men and women

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INHALATION TOXICOLOGY 2000年第8期12卷 715-731页

作者： Jaques, PA Kim, CS US EPA Human Studies Div Natl Hlth & Environm Effects Res Lab Res Triangle Pk NC 27711 USA Univ N Carolina Ctr Environm Med & Lung Biol Chapel Hill NC USA

Ultrafine particles (< 0.10 mu m in diameter) are present in great number in polluted urban air, thus posing a potential health risk. In this study, the total deposition fraction (TDF) of ultrafine aerosols with a narrow size distribution (number median diameter NMD = 0.04- 0.1 mu m and geometric standard deviation sigma(g) = similar to 1.3) was measured in a group of young healthy adults (11 men and 11 women). TDF was obtained with 6 different breathing patterns: tidal volume (V-t) of 500 ml at respiratory flow rates (Q) of 150 and 250 ml/s;V-t = 750 ml at Q of 250 and 375 ml/s;and V-t = 1 L at Q of 250 and 500 ml/s. Aerosols were monitored continuously by a modified condensation nuclei counter while subjects were inhaling them with prescribed breathing patterns. For a given breathing pattern, TDF increased as particle size decreased, regardless of the breathing pattern used. For example, with V-t = 500 ml and Q = 250 ml/s, TDF (mean +/- SD) was 0.26 +/- .04, 0.30 +/- .05, 0.35 +/- .05, and 0.44 +/- .07 for NMD = 0.10, 0.08, 0.06, and 0.04 mu m, respectively. For a given NMD, TDF increased with an increase in V-t and a decrease in Q. TDF was greater for women than men at NMD = 0.04 mu m within all breathing patterns used (p < .05), but the difference was smaller or negligible for larger sized particles. The results suggest that the TDF of ultrafine particles increases with a decrease of particle size and with breathing patterns of longer respiratory time, a pattern that is consistent with diffusion deposition of ultrafine particles. The results also suggest that there is a differential lung dose of ultrafine particles and thus there may be a differential health risk for men versus women.

关键词：气雾剂空气污染物/分类空气污染物/代谢气道阻力/药物作用剂量效应关系药物吸入暴露肺/代谢粒子大小体积描记术全身肺通气性征潮气量肺总量/药物作用成年人女(雌)性人类男(雄)性

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Calf and forearm blood flow in hypercholesterolemic patients

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ANGIOLOGY 2000年第4期51卷 309-318页

作者： Cortella, A Zambon, S Sartore, G Piarulli, F Calabrò, A Manzato, E Crepaldi, G Univ Padua Dept Internal Med I-35128 Padua Italy

Patients with hypercholesterolemia without vascular disease have an impaired endothelium-dependent (nitric oxide-mediated) vasodilation in coronary and peripheral vascular beds. This study was designed to establish whether hypercholesterolemia (and its reduction) affects also the microcirculation vasomotion during postischemic hyperemia in both calf and forearm. Thirteen male patients, aged 36.2 +/- 8.5 years, mean +/- SD, with heterozygous familial hypercholesterolemia and 10 male control subjects, aged 32.2 +/- 3.6 years free from vascular lesions were studied. Plasma lipids, hematologic parameters, and limb vasoreactivity were evaluated while the patients were treated only with diet and during therapy with simvastatin. Calf and forearm blood flows were determined by venous occlusion strain gauge plethysmography at rest, during reactive hyperemia, and after sublingual isosorbide dinitrate administration. Calf resting flow rate of the hypercholesterolemic patients during: and without treatment was similar to that of the controls. Calf resting vascular resistance was greater in the untreated hypercholesterolemic subjects than in the normal controls, but during treatment this difference was abolished. Peak flow during reactive hyperemia and flow debt repayment were lower in the untreated hypercholesterolemic subjects as compared to the controls, but they were normalized following hypocholesterolemic therapy. No differences were observed in forearm blood flow measurements between hypercholesterolemic subjects (without and during therapy) and control subjects. The blood flow and vascular resistance after isosorbide dinitrate were modified in a similar manner in the hypercholesterolemic (without and during therapy) and control subjects at both calf and forearm. Hypercholesterolemia does not affect vasodilation in the forearm as determined by postocclusive reactive hyperemia, while in the calf hypercholesterolemia is associated with higher resting vascular resistance, lo

关键词：前臂/血液供给充血/病理生理学高胆固醇血症Ⅱ型/病理生理学腿/血液供给微循环体积描记术局部血流血管阻力成年人人类男(雄)性

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SB 239063, a potent p38 MAP kinase inhibitor, reduces inflammatory cytokine production, airways eosinophil infiltration, and persistence

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第1期293卷 281-288页

作者： Underwood, DC Osborn, RR Kotzer, CJ Adams, JL Lee, JC Webb, EF Carpenter, DC Bochnowicz, S Thomas, HC Hay, DWP Griswold, DE SmithKline Beecham Pharmaceut Dept Pulm Pharmacol King Of Prussia PA 19406 USA SmithKline Beecham Pharmaceut Dept Med Chem King Of Prussia PA 19406 USA SmithKline Beecham Pharmaceut Dept Bone Biol King Of Prussia PA 19406 USA SmithKline Beecham Pharmaceut Dept Safety Assessment King Of Prussia PA 19406 USA

The anti-inflammatory/antiallergic activity of a novel second-generation p38 mitogen-activated protein kinase inhibitor, SB 239063 [trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl methoxypyridimidin-4-yl)imidazole], was investigated in vivo and in vitro. SB 239063 had an IC50 of 44 nM for inhibition of recombinant purified human p38 alpha. In lipopolysaccharide-stimulated human peripheral blood monocytes, SB 239063 inhibited interleukin-1 and tumor necrosis factor-alpha production (IC50 values = 0.12 and 0.35 mu M, respectively). A role for p38 kinase in cytokine-associated inflammation in the mouse was shown by p38 activation in the lung and inhibition of lipopolysaccharide-induced tumor necrosis factor-a production by SB 239063 (ED50 = 5.8 mg/kg p.o.). Antiallergic activity was demonstrated by essential abolition (similar to 93% inhibition) of inhaled ovalbumin (OA)-induced airway eosinophilia by SB 239063 (12 mg/kg p.o.), measured by bronchoalveolar lavage (BAL) in OA-sensitized mice. In addition, p38 kinase was found by Western analysis to be activated in guinea pig lung. Administration of SB 239063 (10 or 30 mg/kg p.o.) in conscious guinea pigs markedly reduced (similar to 50% inhibition) OA-induced pulmonary eosinophil influx, measured by BAL 24 h after antigen. SB 239063 (10 mg/kg b.i.d. p.o.) administered after leukotriene D-4 inhalation, reduced by 60% the persistent airway eosinophilia seen at 4 days. Apoptosis of cultured eosinophils isolated from guinea pig BAL was increased by SB 239063 (1-10 mu M) in the presence of interleukin-5. These results indicate that SE 239063 is a potent inhibitor of inflammatory cytokine production, inhibits eosinophil recruitment, in addition to enhancing apoptosis of these cells. Collectively, the results support the potential utility of p38 kinase inhibitors, such as SE 239063, for the treatment of asthma and other inflammatory disorders.

关键词：投药吸入细胞凋亡/药物作用印迹法蛋白质支气管肺泡灌洗液/细胞学支气管收缩/药物作用细胞因子类/生物合成酶抑制剂/药理学嗜酸粒细胞增多/化学诱导嗜酸粒细胞增多/病理学咪唑类/药理学白三烯D4/投药和剂量白三烯D4/药理学脂多糖类/药理学小鼠近交BALBC 丝裂原激活蛋白激酶类单核细胞/药物作用单核细胞/代谢吞噬作用/药物作用体积描记术全身嘧啶类/药理学呼吸系统/药物作用呼吸系统/病理学肿瘤坏死因子α/生物合成 p38丝裂原活化蛋白激酶类动物豚鼠人类小鼠

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Effects of passive tilting on capillary filtration in the lower leg in idiopathic dilated cardiomyopathy and after heart transplantation for the same condition

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第11期84卷 1328-1334页

作者： Galatius, S Wroblewski, H Sorensen, VB Arendrup, H Kastrup, J Rigshosp Heart Ctr B2014 DK-2100 Copenhagen 0 Denmark

Abnormal reflex control of the peripheral microvasculature during orthostasis in congestive heart failure (CHF) and after heart transplantation (HT) may cause failure of microvascular homeostasis and peripheral edema. We explored the effect of passive head-vp tilt on lower leg capillary filtration measured by strain-gauge plethysmography in 24 patients with CHF, in 20 patients after HT (12 patients with preserved native right atrium, 8 patients without native right atrium), and in 18 controls. We hypothesized that an impaired peripheral microvascular reflex during orthostasis in CHF and Hi might allow increased arterial hydrostatic pressure to increase pressure at the capillary level. To identify an impact of changes in arterial hydrostatic pressure, capillary fluid filtration was expressed per mm Hg arterial hydrostatic pressure (capillary filtration coefficient(arterial pressure) [CFCAP]) and was measured (1) during elevated venous pressure alone (50 mm Hg venous stasis in supine position), and (2) during elevated hydrostatic pressure at both the venous and arterial side of the vascular tree (head-up tilt with a vertical distance from the right atrium to the strain-gauge of 68 cm of water [50 mmHg]). Elevated venous pressure alone resulted in the highest CFCAP in controls (0.79 +/- 0.28 ml/min 100 ml mm Hg . 10(-3) +/- SD) versus those with CHF (0.44 +/- 0.23, p <0.0001) and those after HT (0.54 +/- 0.22, p <0.01). However, during head-vp tilt, CFCAP was similar in all 3 groups, because CFCAP decreased in controls (to 0.49 +/- 0.22, p <0.0001), in contrast to unchanged CFCAP in those with CHF (0.43 +/- 0.24) and in those with HT (0.50 +/- 0.21). HT patients with complete removal of the native right atrium had higher CFCAP (0.62 +/- 0.17) during head-up tilt than patients with preserved native right atrium (0.36 +/- 0.16, p <0.005). In conclusion, patients with CHF and those after HT have increased capillary filtration to a lesser degree than controls during elevat

关键词：血压毛细血管/病理生理学心肌病扩张型/病理生理学心肌病扩张型/外科学水肿/病理生理学心脏移植流体静力压腿/血液供给微循环体积描记术体位/生理学预后倾斜台试验时间因素成年人女(雌)性人类男(雄)性中年人

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PSYCHOPHYSIOLOGIC EFFECTS OF ACUTE CANNABIS SMOKING IN LONG-TERM USERS

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1976年第DEC30期282卷 375-386页

作者： LIAKOS, A BOULOUGOURIS, JC STEFANIS, C UNIV ATHENS EGINITION HOSPSCH MEDDEPT PSYCHIATATHENSGREECE

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Impaired forearm reactive hyperemia is related to late restenosis after coronary stenting

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AMERICAN JOURNAL OF CARDIOLOGY 2000年第9期85卷 1071-1076页

作者： Wu, TC Chen, YH Chen, JW Chen, LC Lin, SJ Ding, PYA Wang, SP Chang, MS Taipei Vet Gen Hosp Dept Med Div Cardiol Taipei Taiwan Natl Yang Ming Univ Sch Med Taipei 112 Taiwan

To investigate whether systemic endothelial function on forearm resistance vessels is related to angiographic restenosis after coronary stenting, 47 men who underwent elective coronary stenting were divided into 2 groups according to the presence (n = 20) or absence (n = 27) of in-stent restenosis 6 months after the procedure. Another 19 risk factor-matched men with normal coronary angiograms served as the control group. Forearm blood flow was assessed by venous occlusive plethysmography. Basal forearm blood flow was similar between restenosis, nonrestenosis, and control groups (2.63 +/- 0.19, 2.58 +/- 0.14, and 3.23 +/- 0.13 ml/100 mi forearm tissue per minute, respectively). In all 3 groups, forearm blood flow increased significantly during reactive hyperemia (5.75 +/- 0.7, 11.32 +/- 1.23, and 14.52 +/- 1.36 ml/100 mi forearm tissue per minute, p <0.05, respectively) and remained unchanged after sublingual administration of nitroglycerin. The percentage change of forearm blood flow during reactive hyperemia was significantly lower in the restenosis group (117.3 +/- 18.3%) than in the nonrestenosis group (354.2 +/- 46.5%, p <0.01). This difference was still present after sublingual nitroglycerin (37.6 +/- 21.2% vs 226.4 +/- 40.5%, p <0.01). In contrast, percentage change of hyperemic forearm blood flow was significantly lower in patients with angina (117.5 +/- 49.5%) than in those without angina (290.1 +/- 37.4%, p <0.05) at follow-up. In all patients, the angiographic loss index was correlated negatively to the percentage change of hyperemic forearm blood flow (r = -0.33, p <0.01) and positively to the percentage change of forearm vascular resistance during reactive hyperemia (r = 0.33, p <0.01). In patients with angiographic restenosis after coronary stenting, forearm reactive hyperemia was more impaired compared with those without angiographic restenosis. Systemic endothelial dysfunction might be either a marker or one of the confounding factors in the developme

关键词：冠状血管造影术冠心病/病理生理学冠心病/治疗内皮血管/病理生理学前臂/血液供给充血/病因学体积描记术复发支架老年人女(雌)性人类男(雄)性中年人

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Withholding treatment in patients with acute pulmonary embolism who have a high risk of bleeding and negative serial noninvasive leg tests

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AMERICAN JOURNAL OF MEDICINE 2000年第4期109卷 301-306页

作者： Stein, PD Hull, RD Raskob, GE St Joseph Mercy Oakland Hosp Pontiac MI USA Univ Calgary Sch Med Calgary AB Canada Univ Oklahoma Hlth Sci Ctr Dept Med Oklahoma City OK USA Univ Oklahoma Hlth Sci Ctr Dept Biostat Oklahoma City OK USA Univ Oklahoma Hlth Sci Ctr Dept Epidemiol Oklahoma City OK USA

PURPOSE: Patients who have nonmassive acute pulmonary embolism and a high risk of bleeding or contraindication to anticoagulants, such recent surgery or gastrointestinal bleeding, present a clinical dilemma. We sought to estimate whether such patients could be safely left untreated if serial compression ultrasound or serial impedance plethysmography were negative and cardiorespiratory reserve was adequate. SUBJECTS AND METHODS: The frequency of recurrent pulmonary embolism among patients with nonmassive acute pulmonary embolism and negative serial noninvasive leg tests who were not treated was estimated from two prospective studies of the noninvasive management of patients with suspected pulmonary embolism. One of the studies used serial impedance plethysmography of the lower extremities;the other used serial compression ultrasound. The prevalence of pulmonary embolism in patients with nondiagnostic ventilation/perfusion lung scans was determined from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). RESULTS: The estimated frequency of fatal recurrent pulmonary embolism was 1% [95% confidence interval (CI), 0% to 5%) among untreated patients with nonmassive pulmonary embolism who had negative serial impedance plethysmograms and 0% (95% CI, 0% to 4%) among those with negative serial compression ultrasonograms. The frequency of nonfatal recurrent pulmonary embolism among untreated patients was 3%, regardless of whether they had negative serial impedance plethysmograms or negative serial compression ultrasonograms. These results were comparable with the frequency of recurrent pulmonary embolism among patients treated with anticoagulants or with inferior vena cava filters. CONCLUSION: Withholding treatment of nonmassive acute pulmonary embolism, if serial impedance plethysmograms or serial venous ultrasonograms are negative and cardiopulmonary reserve is adequate, is a possible strategy for the management of patients with a high risk of bleeding or

关键词：急性病抗凝药/投药和剂量抗凝药/禁忌证脑出血/化学诱导脑出血/预防和控制出血/病因学出血/预防和控制腿肺/超声检查体积描记术试验预期值预后前瞻性研究肺栓塞/并发症肺栓塞/诊断肺栓塞/药物疗法复发危险性评估敏感性与特异性治疗结果成年人老年人女(雌)性人类男(雄)性中年人

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Leg venous hemodynamics and leg volumes during a 42-day -6 degrees head-down bedrest

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ACTA ASTRONAUTICA 1995年第8-12期36卷 575-579页

作者： Louisy, F Schroiff, P Guezennec, CY Guell, A Centre National d'Etudes Spatiales 31055 Toulouse France

Seven healthy subjects were submitted to a 42-day head down bedrest, where leg venous compliance (venous distensibity index VDI) and leg volumes were assessed by mercury strain gauge plethysmography with venous occlusion and optoelectronic plethysmography, respectively. Plethysmographic and volometric measurements were made, before, during (at days 1, 4, 7, 14, 21, 26, 34 and 41), and after bedrest (days 1, 4, 7, 11 and 30 of the recovery period). Results showed a continuous decrease in leg volumes throughout bedrest, when VDI increased until day 26 of bedrest, and then decreased afterwards. The recovery period was characterized by a rapid return of VDI to prebedrest levels while leg volumes progressively normalised. These results showed that leg venous compliance changes are not always dependant upon skeletal muscle changes, and that factors other than size of muscle compartment are able to determine increases in leg venous compliance during long-term bedrest.

关键词：适应生理学卧床休息血量/生理学顺应性头低位血流动力学/生理学腿/血液供给腿/生理学肌骨骼/解剖学和组织学肌骨骼/血液供给肌骨骼/生理学肌平滑/血液供给肌平滑/生理学体积描记术失重模拟成年人人类男(雄)性

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Basic fibroblast growth factor in patients with intermittent claudication: Results of a phase I trial

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第4期36卷 1239-1244页

作者： Lazarous, DF Unger, EF Epstein, SE Stine, A Arevalo, JL Chew, EY Quyyumi, AA NHLBI Cardiol Branch NIH Bethesda MD 20892 USA NEI NIH Bethesda MD 20892 USA

OBJECTIVES This phase I study was designed to evaluate the safety, tolerability and pharmacokinetics of intra-arterial basic fibroblast growth factor (bFGF) in patients with atherosclerotic peripheral arterial disease (PVD) and intermittent claudication. We also assessed the effects of basic fibroblast growth factor (bFGF) on calf blood flow as a measure of biologic activity. BACKGROUND Preclinical studies have shown that bFGF, an angiogenic peptide, promotes collateral development in animal models of myocardial and hind limb ischemia. The safety and efficacy of bFGF in patients is unknown, and early clinical trials are underway in coronary and peripheral arterial disease. METHODS A double-blind, placebo-controlled, dose-escalation trial was conducted in patients with claudication demonstrating ankle/brachial index <0.8. Patients were randomly assigned to placebo (n = 6), 10 mu g/kg of bFGF (n = 4), 30 mu g/kg of bFGF once (n = 5) and 30 mu g/kg of bFGF on two consecutive days (n = 4). Study drug was infused into the femoral artery of the ischemic leg. Detailed safety information including retinal photography for neovascularization were obtained through one year. Calf blood flow was measured with strain gauge plethysmography in the two higher dose treatment groups and in four placebo patients at baseline, one month and three to seven months after treatment. RESULTS Intra-arterial bFGF was safe and well-tolerated. The half-life was 46 +/- 21 min. Calf blood flow increased at one month by 66 +/- 26% (mean +/- SEM) and at six months by 153 +/- 51% in bFGF-treated patients (n = 9, p = 0.002). Flow did not change significantly in the placebo group. CONCLUSIONS In this initial randomized, double-blind, placebo-controlled trial in patients with atherosclerotic PVD and claudication, bFGF was well-tolerated. The data suggest a salutary biologic effect, and initiation of phase 2 trials is warranted. (J Am Coil Cardiol 2000;36:1239-44) (C) 2000 by the American College of Cardi

关键词：踝/血液供给血流速度/药物作用肱动脉/药物作用肱动脉/病理生理学双盲法成纤维细胞生长因子2/投药和剂量成纤维细胞生长因子2/药代动力学半衰期注射动脉内间歇性跛行/血液间歇性跛行/药物疗法间歇性跛行/病理生理学体积描记术安全老年人女(雌)性人类男(雄)性

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