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Time course of endothelin-1 and adrenomedullin after the Fontan procedure

ANNALS OF THORACIC SURGERY 1999年第1期68卷 169-172页

作者： Hiramatsu, T Imai, Y Takanashi, Y Seo, K Terada, M Aoki, M Nakazawa, M Tokyo Womens Med Univ Heart Inst Japan Dept Pediat Cardiac Surg Shinjuku Ku Tokyo 1628666 Japan Tokyo Womens Med Univ Heart Inst Japan Dept Cardiol Shinjuku Ku Tokyo 1628666 Japan

Background. The endothelium-derived vasoconstrictor endothelin (ET)-1 might contribute to the physiology of blood flow regulation and play a role in cardiovascular disease. Adrenomedullin (AM) is a potent vasodilator peptide that has major effects on cardiovascular function and has multiple biologic effects involved in cardiovascular homeostasis. Although pulmonary vascular resistance is known to be one of the most important factors to determine the indications for a Fontan procedure, the time course of the plasma cytokine before and after the Fontan procedure is not known. Methods. Sixteen patients were divided into two groups, 8 patients (1 to 14 years) who had the Fontan procedure (atriopulmonary connection) and 8 age-matched controls who had biventricular repair with normal central venous pressure. Plasma ET-1 and adrenomedullin levels were measured in both groups immediately before cardiopulmonary bypass, immediately after cardiopulmonary bypass, and 6 and 24 hours after cardiopulmonary bypass. A thermodilution catheter was inserted during the operation, and mean pulmonary arterial pressure, pulmonary wedge pressure, and cardiac output were measured, and pulmonary vascular resistance was calculated at the same time points. Correlation between the plasma ET-1 levels and pulmonary vascular resistance data were obtained in the Fontan group. Results. Plasma ET-1 levels in the Fontan group were elevated after operation and were higher than the control group at 6 and 24 hours after cardiopulmonary bypass. Plasma adrenomedullin in the Fontan group was lower than in the control group at 6 and 24 hours after cardiopulmonary bypass. A significant positive correlation was obtained between the plasma ET-1 and pulmonary vascular resistance data (r = 0.475). Conclusions. Imbalance between increased ET-1 and relatively decreased adrenomedullin after cardiopulmonary bypass in the Fontan procedure could contribute to dominant effects of ET-1, which might induce vasoconstriction

关键词：肾上腺髓质素心肺转流术内皮缩血管肽1/血液内皮缩血管肽1/生理学 Fontan手术肽类/血液肽类/生理学肺循环时间因素血管收缩/生理学血管舒张/生理学青少年儿童儿童学龄前人类婴儿

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Neurogenic vasodilatation of canine isolated small labial arteries

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 1999年第3期288卷 1031-1036页

作者： Okamura, T Ayajiki, K Uchiyama, M Uehara, M Toda, N Shiga Univ Med Sci Dept Pharmacol Ohtsu Shiga 5202192 Japan Shiga Univ Med Sci Dept Dermatol Ohtsu Shiga 5202192 Japan

Mechanisms underlying vasodilatation to nerve stimulation by electrical pulses and nicotine were analyzed in isolated canine small labial arteries. Transmural electrical stimulation (5 and 20 Hz) produced a contraction followed by a relaxation in labial arterial strips denuded of the endothelium, partially contracted with prostaglandin F-2 alpha. The contraction was abolished by prazosin or combined treatment with alpha, beta-methylene ATP. In the treated strips, neurogenic relaxation was abolished by N-G-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor, and restored by L-arginine. The D-enantiomers were without effect. Nicotine (10(-4) M) also relaxed the arteries, in which the contractile response was abolished by prazosin and alpha,beta-methylene ATP. The relaxant response was attenuated but not abolished by L-NA;the inhibition was reversed by L-arginine. The remaining relaxation by nicotine was abolished by calcitonin gene-related peptide (CGRP)-[8 to 37], a CGRP, receptor antagonist. Relaxations elicited by a lower concentration of nicotine (2 x 10(-5) M) sufficient to produce similar magnitudes of response to those induced by 5-Hz electrical nerve stimulation were also inhibited partially by L-NA. Histochemical study with the NADPH-diaphorase method demonstrated positively stained nerve fibers and bundles in the arterial wall, suggesting the presence of neuronal NO synthase. It is concluded that the relaxation induced by electrical nerve stimulation of small labial arteries is mediated exclusively by NO synthesized from L-arginine in nerve terminals, whereas nicotine in the concentrations used evokes relaxations by a mediation of nerve-derived NO and also CGRP, possibly from sensory nerves. The reason why nicotine but not electrical pulses stimulates sensory nerves and elicits vasorelaxation remains unsolved.

关键词：地诺前列素电刺激组织细胞化学唇系带/血液供给上颌动脉/神经支配肌平滑血管/神经支配尼古丁/药理学硝基精氨酸/药理学皮肤/血液供给血管舒张/生理学动物狗

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Mechanisms of hypoxic vasodilatation of isolated rat mesenteric arteries: a comparison with metabolic inhibition

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JOURNAL OF PHYSIOLOGY-LONDON 1999年第1期516卷 249-259页

作者： Otter, D Austin, C Manchester Royal Infirm Dept Med Manchester M13 9WL Lancs England

1. Hypoxia (P-O2 < 5 mm Hg) decreased vessel tone in isolated rat mesenteric arteries precontracted with either high [K+] or the thromboxane analogue U46619. This response was not altered by N-nitro-L-arginine (L-NA) and indomethacin. 2. Simultaneous measurement of pH(i) and tension showed that the decrease in vessel tone was accompanied by an intracellular acidification. Similar reductions in tone and pH(i) were observed with the metabolic inhibitors 2,4-dinitrophenol (DNP) and sodium azide. 3. The presence of the lactate transport inhibitor alpha-cyano-4-hydroxy-cinnamic acid (CHC) increased the magnitude of the acidification and resulted in a significantly faster reduction in tone in response to hypoxia. Addition of CHC to normoxic tissues caused both a vasodilatation and a reduction of pH(i). 4. A decrease in pH(i) induced on washout of ammonium chloride (NH4Cl) resulted in an increase in tone. 5. Relaxation to hypoxia or metabolic inhibition was unaffected when the change in pH(i) was neutralized by addition of the weak base trimethylamine (TMA). 6. It is concluded that severe hypoxia decreases tone in isolated rat mesenteric arteries by a mechanism which is independent of nitric oxide and prostaglandins. Both severe hypoxia and metabolic inhibition reduced pH(i), although this does not appear to be contributing to the changes in tone observed.

关键词： 15-羟基-11α 9α-(环氧亚甲基)前列腺-5 13-二烯酸/药理学 2 4-二硝基苯酚/药理学氯化铵/药理学缺氧/病理生理学抗代谢药/药理学氢离子浓度肠系膜动脉/药物作用肠系膜动脉/病理生理学甲胺类/药理学肌收缩/药物作用肌松弛/药物作用一氧化氮/生理学钾/药理学大鼠 Wistar 解偶联药/药理学血管舒张/药物作用血管舒张/生理学动物男(雄)性大鼠

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Attenuated coronary flow reserve and vascular remodeling in patients with hypertension and left ventricular hypertrophy

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第6期35卷 1654-1660页

作者： Hamasaki, S Al Suwaidi, J Higano, ST Miyauchi, K Holmes, DR Lerman, A Mayo Clin & Mayo Fdn Ctr Coronary Physiol & Imaging Div Cardiovasc Dis Dept Internal Med Rochester MN 55905 USA

OBJECTIVES The purpose of this study was to evaluate the association between hypertension and left ventricular hypertrophy (LVH) with both coronary vascular remodeling and endothelial function. BACKGROUND The association between endothelial and nonendothelial coronary flow reserve with vascular remodeling in patients with hypertension and LVI-I is still unclear. METHODS One hundred and eleven patients with normal or mildly diseased coronary arteries at angiography underwent intravascular ultrasound examination of the left anterior descending coronary artery. Patients were divided into three groups: group I: n = 13, hypertensive patients with LVH;group 2: n 30, hypertensive patients without LVH;group 3: n 68, normotensive patients. Vessel and lumen area and atherosclerotic plaque area were evaluated. Vascular reactivity was examined using intracoronary adenosine and acetylcholine. RESULTS Vessel area in group 1 (with LVH) was significantly (p < 0.01) greater than that in group 2 (without LVH), whereas, vessel area in both groups 1 and 3 was similar (12.8 +/- 0.8 mm(2), 10.7 +/- 0.4 mm(2) and 11.5 +/- 0.3 mm(2)). Coronary blood flow at baseline for patients in group 1 (with LVH) was significantly greater than it was for patients in groups 2 and 3 (81.1 +/- 9.9 ml/min, 56.5 +/- 6.2 ml/min and 48.1 +/- 3.2 ml/min, both p < 0.05). In comparison with groups 2 and 3, the response to both acetylcholine and adenosine was significantly impaired in patients with LVH. CONCLUSIONS The current study demonstrates that hypertension with LVH is associated with both coronary vascular remodeling and attenuated endothelial and nonendothelial coronary flow reserve. (C) 2000 by the American College of Cardiology.

关键词：乙酰胆碱腺苷冠状血管造影术冠状动脉疾病/诊断冠状动脉疾病/病理生理学冠状动脉循环/生理学冠状血管/病理生理学腔内超声检查内皮血管/病理生理学高血压/诊断高血压/病理生理学肥大左心室/诊断肥大左心室/病理生理学前瞻性研究血管舒张/生理学心室功能左/生理学女(雌)性人类男(雄)性中年人

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Inhibitory effects of low-density lipoproteins from men with type II diabetes on endothelium-dependent relaxation

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第6期35卷 1622-1627页

作者： McNeill, KL Fontana, L Russell-Jones, DL Rajman, I Ritter, JM Chowienczyk, PJ Univ London Kings Coll Ctr Cardiovasc Biol & Med Dept Clin Pharmacol London WC2R 2LS England Univ London Kings Coll Dept Endocrinol & Diabet London WC2R 2LS England

OBJECTIVE The object of the present study is to determine whether native (n) low-density lipoprotein (LDL) isolated from men with type n: diabetes and abnormal endothelial function inhibits endothelium-dependent relaxation more than n-LDL isolated from nondiabetic control subjects. BACKGROUND Endothelium-dependent vasodilation is impaired in men with type II diabetes and this may result from qualitative rather than quantitative abnormalities of LDL. METHODS Forearm blood flow responses to brachial artery infusions of acetylcholine (endothelium-dependent vasodilator) and nitroprusside (endothelium-independent vasodilator) were measured in 10 men with uncomplicated type II diabetes and 10 nondiabetic men of similar age and with similar plasma concentrations of LDL cholesterol. Native LDL was isolated by discontinuous density gradient ultracentrifugation using EDTA to prevent oxidation. Preconstricted rabbit aortic ring bioassay was used to determine inhibitory properties of n-LDL on endothelium-dependent relaxation by measuring relaxation to acetylcholine (and nitroprusside) in the presence and absence of n-LDL. RESULTS Forearm blood flow responses to acetylcholine but not nitroprusside were significantly impaired (p < 0.01) in diabetic men compared with control subjects. Native LDL (10 and 100 mu g protein/ml) from diabetic men inhibited relaxation to acetylcholine by 13.9 +/- 4.8% and 61.9 +/- 7.8% (mean inhibition for all doses +/- SE), respectively, whereas n-LDL from control subjects inhibited relaxation by 7.3 +/- 3.0% and 23.9 +/- 5.7% (p < 0.01 for a difference between diabetic and control n-LDL). Relaxation to nitroprusside was not significantly inhibited by n-LDL. CONCUSIONS A qualitative abnormality of LDL may account for endothelial dysfunction in men with type II diabetes. (C) 2000 by the American College of Cardiology.

关键词：乙酰胆碱胆固醇 LDL/血液培养技术糖尿病 2型/病理生理学糖尿病血管病变/病理生理学内皮血管/病理生理学前臂/血液供给硝普钠血管舒张/生理学动物人类男(雄)性中年人兔

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Sustained infection induces 2 distinct microvascular mechanisms in the splanchnic circulation

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SURGERY 2000年第4期128卷 513-518页

作者： Zhao, HL Spain, DA Matheson, PJ Vaughn, C Harris, PD Garrison, RN Univ Louisville Dept Surg Louisville KY 40292 USA Univ Louisville Dept Physiol & Biophys Louisville KY 40292 USA Univ Louisville Ctr Excellence Appl Microcirculatory Res Louisville KY 40292 USA Vet Affair Med Ctr Louisville KY USA

Background. Altered intestinal bloodflow during systemic inflammation leads to organ dysfunction. Mucosal ischemia occurs during sepsis despite an increase in portal blood flow. We hypothesized that separate mechanisms are active in the large resistance and small mucosal microvessels to account for this dichotomy. Methods. Chronic infection was induced in rats by bacterial inoculation (Escherichia coli and Bacteroides fragilis) of an implanted subcutaneous sponge. Separate groups were studied at 24 and 72 hours after a single inoculation of bacterium or 24 hours after a second inoculation tie, 72 hours of sepsis). Time-matched controls were used for each group. Intravital microscopy of the terminal ileum was used to assess endothelial-dependent vasodilation to acetylcholine (10(-9) to 10(-5) mol/L) resistance (A(1)) and premucosal (A(3)) arterioles. Threshold sensitivity (-log of 20% response dose) was calculated from dose response curves for each animal. Results. Vasodilator sensitivity to acetylcholine in A(1) arterioles was significantly decreased at 24 hours, and these changes persisted up to 72 hours after a single bacterial inoculation. There was no change in the dilator sensitivity of A(3) arterioles after a single inoculation. When. there was a challenge with a second bacterial inoculation, there was a reversal of the A(1) dilator response and an increase in A(3) sensitivity. Conclusions. An initial septic event results in a decrease in dilator reactivity in the resistance A(1) arterioles that;persists for at least 72 hours. A sustained septic challenge results in increased dilator reactivity in both A(1) and A(3) vessels. This enhanced sensitivity during sepsis suggests that more than 1 therapeutic approach to preservation of intestinal bloodflow will be necessary.

关键词：乙酰胆碱/药理学拟杆菌感染/代谢拟杆菌感染/病理生理学拟杆菌脆弱大肠杆菌感染/代谢大肠杆菌感染/病理生理学肠黏膜/血液供给肠黏膜/酶学肠黏膜/病理生理学显微镜检查电视一氧化氮/代谢一氧化氮合酶/代谢大鼠 Sprague-Dawley 脓毒症/代谢脓毒症/病理生理学内脏循环/生理学血管舒张/药物作用血管舒张/生理学血管舒张药/药理学动物男(雄)性大鼠

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Coronary artery distensibility in diabetic patients with simultaneous measurements of luminal area and intracoronary pressure - Evidence of impaired reactivity to nitroglycerin

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第4期34卷 1075-1081页

作者： Vavuranakis, M Stefanadis, C Triandaphyllidi, E Toutouzas, K Toutouzas, P Univ Athens Hipprokrat Hosp Dept Cardiol Athens Greece

OBJECTIVE This study investigated whether noninsulin dependent diabetes mellitus (NIDDM) adversely affects the elastic properties of the coronary arteries in patients with coronary artery disease (CAD) and NIDDM. BACKGROUND Attenuated vascular smooth muscle dilation to exogenous donors of nitric oxide, such as nitroglycerin, has been observed with forearm blood flow studies in patients with NIDDM. METHODS Twenty patients with CAD and NIDDM (diabetics), and 20 patients with only CAD (nondiabetics) were evaluated. Intracoronary ultrasound (ICUS) imaging with simultaneous intracoronary pressure (P-2) recordings were performed at the imaging site with 0.014 in fiber-optic high fidelity pressure monitoring wire. The same wire was used as guide wire for the ICUS catheter. Sites with less than 50% luminal stenosis by ICUS were studied. Recordings were done before and after 300 mu g of intracoronary nitroglycerin (IC-NTG). Electrocardiographic tracings recorded simultaneously with ICUS images were used for timing. Systolic and diastolic cross-sectional lumen area (CSLA) and coronary artery distensibility (C-DIST) were measured, C-DIST = {(systolic CSLA-diastolic CSLA)/[(intracoronary pulse pressure) x (diastolic CSLA)]} x 1,000. RESULTS Diabetics had smaller CSLA (diabetics = 8.6 +/- 0.6 mm(2), nondiabetics = 11.5 +/- 0.5 mm(2), p < 0.01). Although C-DIST was similar before IC-NTG in the two groups, it became significantly lower in diabetics after IC-NTG (diabetics C-DIST = 3.02 +/- 0.14 mm Hg-1 nondiabetics C-DIST = 4.21 +/- 0.15 mm Hg-1, p < 0.01). Degrees of circumference involved, total plaque burden and composition were similar in both groups. CONCLUSIONS Noninsulin dependent diabetes mellitus reduces C-DIST after IC-NTG administration. (J Am Coll Cardiol 1999;34:1 075-81) (C) 1999 by the American College of Cardiology.

关键词：血压/生理学冠心病/诊断显像冠心病/病理生理学冠状血管/生理学糖尿病 2型/诊断显像糖尿病 2型/病理生理学糖尿病血管病变/诊断显像糖尿病血管病变/病理生理学心舒期/生理学弹性心电描记术腔内超声检查/仪器和设备一氧化氮/生理学硝酸甘油观察者偏差心缩期/生理学血管舒张/生理学血管舒张药成年人老年人女(雌)性人类男(雄)性中年人

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Correction of endothelial dysfunction in chronic heart failure: Additional effects of exercise training and oral L-arginine supplementation

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第3期35卷 706-713页

作者： Hambrecht, R Hilbrich, L Erbs, S Gielen, S Fiehn, E Schoene, N Schuler, G Univ Leipzig Ctr Heart Div Cardiol D-04289 Leipzig Germany

OBJECTIVES The aim of this study was to analyze whether L-arginine (L-arg.) has comparable or additive effects to physical exercise regarding endothelium dependent vasodilation in patients with chronic heart failure (CHF). BACKGROUND Endothelial dysfunction in patients with CHF can be corrected by both dietary supplementation with L-arg. and regular physical exercise. METHODS Forty patients with severe CHF (left ventricular ejection fraction 19 +/- 9%) were randomized to an L-arg. group (8 g/day), a training group (T) with daily handgrip training, L-arg, and T (L-arg. + T) or an inactive control group (C). The mean internal radial artery diameter was determined at the beginning and after four weeks in response to brachial arterial administration of acetylcholine (ACh) (7.5, 15, 30 mu g/min) and nitroglycerin (0.2 mg/min) with a transcutaneous high-resolution 10 MHz A-mode echo tracking system coupled with a Doppler device. The power of the study to detect clinically significant differences in endothelium-dependent vasodilation was 96.6%. RESULTS At the beginning, the mean endothelium-dependent vasodilation in response to ACh, 30 mu g/min was 2.54 +/- 0.09% (p = NS between groups). After four weeks, internal radial artery diameter increased by 8.8 +/- 0.9% after ACh 30 mu g/min in L-arg. (p < 0.001 vs. C), by 8.6 +/- 0.9% in T (p < 0.001 vs. C) and by 12.0 +/- 0.3% in L-arg, + T (p < 0.005 vs. C, L-arg. and T). Endothelium independent vasodilation as assessed by infusion of nitroglycerin was similar in all groups at the beginning and at the end of the study. CONCLUSIONS Dietary supplementation of L-arg. as well as regular physical exercise improved agonist-mediated, endothelium-dependent vasodilation to a similar extent. Both interventions together seem to produce additive effects with respect to endothelium-dependent vasodilation. (C) 2000 by the American College of Cardiology.

关键词：乙酰胆碱/投药和剂量投药口服精氨酸/投药和剂量精氨酸/药代动力学血流速度内皮血管/药物作用内皮血管/病理生理学运动疗法心力衰竭/血液心力衰竭/病理生理学心力衰竭/康复注射动脉内硝酸甘油/投药和剂量桡动脉/诊断显像桡动脉/药物作用桡动脉/病理生理学每搏输出量治疗结果超声检查多普勒血管舒张/药物作用血管舒张/生理学血管舒张药/投药和剂量老年人人类男(雄)性中年人

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Assessment and treatment of endothelial dysfunction in humans

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第3期34卷 631-638页

作者： Anderson, TJ Univ Calgary Dept Med Div Cardiol Calgary AB Canada Alberta Heritage Fdn Med Res Calgary AB Canada

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Endothelial vasodilator function is related to low-density lipoprotein particle size and low-density lipoprotein vitamin E content in type 1 diabetes

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第2期35卷 292-299页

作者： Skyrme-Jones, RAP O'Brien, RC Luo, M Meredith, IT Monash Med Ctr Ctr Heart & Chest Res Melbourne Vic Australia Monash Med Ctr Dept Med Melbourne Vic Australia Monash Univ Melbourne Vic 3004 Australia

OBJECTIVES We sought to determine whether endothelial vasodilator function (EVF) in patients with type 1 diabetes was related to low-density lipoprotein (LDL) particle size (LDLPS), LDL vitamin E content (LDLVE) or the susceptibility of LDL to oxidation (OxLDL). BACKGROUND Impaired EVF is an early feature of diabetic vascular disease and may be related to oxidant stress. Although small, dense LDL and oxidized LDL are features of type 2 diabetes and predict the development of coronary artery disease, their role in type 1 diabetes is less clear. METHODS Endothelium-dependent vasodilation was assessed in the brachial artery (flow-mediated vasodilation [FMD]) and in the forearm resistance circulation using venous occlusion plethysmography in response to graded doses of intrabrachial acetylcholine (ACh). Thirty-seven patients with type 1 diabetes mellitus (DM) and 45 matched controls underwent flow-mediated dilation, while a subset of 19 DM and 20 controls underwent plethysmography. RESULTS Total, LDL and high-density lipoprotein cholesterol or triglycerides were not different in DM compared with controls, but LDLPS was smaller (25.6 +/- 0.06 vs. 26.1 +/- 0.1 nm, p < 0.05) and LDLVE was reduced (2.0 +/- 0.25 vs. 2.6 +/- 0.18 mu mol/mmol LDL, p < 0.05). Oxidative susceptibility of LDL was not different. Flow-mediated vasodilation was impaired in DM compared with controls (3.6 +/- 0.6% vs. 7.1 +/- 0.5%, p < 0.005), as was the vasodilator response to ACh (p < 0.05). Flow-mediated vasodilation was directly related to LDLPS and LDLVE in both the entire study cohort and DM alone (p < 0.05), but not to other parameters of the standard lipid profile. Similarly, endothelium-dependent vasodilation in the resistance circulation was directly related to LDLPS and LDLVE, but not to OxLDL. CONCLUSION These results suggest, but do not prove, that LDL particle size and LDL vitamin E may be determinants of conduit and resistance vessel endothelial vasodilator function in type 1 diabetes.

关键词：乙酰胆碱/投药和剂量血流速度肱动脉/诊断显像肱动脉/药物作用肱动脉/病理生理学胆固醇 LDL/血液糖尿病 1型/血液糖尿病 1型/病理生理学内皮血管/药物作用内皮血管/病理生理学输注动脉内硝酸甘油/投药和剂量硝普钠/投药和剂量氧化性应激预后危险因素超声检查血管舒张/药物作用血管舒张/生理学血管舒张药/投药和剂量维生素E/血液成年人人类

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