A novel S-nitrosothiol (RIG200) causes prolonged relaxation in dorsal hand veins with damaged endothelium

BACKGROUND: Reduced nitric oxide bioavailability caused by endothelial dysfunction or damage is a contributory factor in the initiation and progression of a number of cardiovascular diseases. Delivery of exogenous nitric oxide is an attractive therapeutic option, but current agents lack selectivity for areas of endothelial damage. We tested the hypothesis that a novel nitric oxide donor drug, N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6-tetra-O-acet yl-P-glucopyranose [RIG200], which has selective effects in endothelium-denuded isolated arteries in vitro, would exert similar effects in dorsal hand veins with experimentally damaged endothelium in vivo. METHODS: Venodilator responses to sodium nitroprusside and RIG200 were compared in two groups of healthy volunteers (age range, 18 to 63 years; n = 7 for each group) in norepinephrine 70% maximum effective concentration (EC70) preconstricted hand veins with use of the Aellig technique. In this doubleblind study, subjects were randomly assigned to receive either sodium nitroprusside or RIG200 (infusions of 0.06 and 6 nmol/min into the hand vein) before and 2 days after 15 minutes of local venous irription with distilled water. Endothelial function was assessed in all subjects on both visits with use of the endothelium-dependent vasodilator acetylcholine (1 nmol/min). RESULTS: Irrigation of hand veins with distilled water abolished endothelium-dependent dilatation in response to acetylcholine in both study groups (n = 14) but did not affect the amplitude or duration of responses to the conventional nitric oxide donor sodium nitroprusside (P = .87; n = 7). However, responses to RIG200 were significantly prolonged during the washout phase (30 minutes) in veins after water irrigation (P = .02; n = 7). CONCLUSION: These studies confirm that RIG200 has prolonged effects in veins with damaged endothelium, a characteristic that might be exploited therapeutically to target nitric oxide delivery to damaged blood vessels.     

ADMA对人脐静脉内皮细胞粘附功能影响的体外研究

目的观察非对称性二甲基精氨酸(ADMA)对体外培养的人脐静脉内皮细胞(HUVECs)粘附功能的影响。方法原代获取HUVECs,分别加入ADMA5μmol/L和10μmol/L培养48小时。测定细胞的数目、粘附和产生一氧化氮的能力。流式细胞仪检测细胞表面粘附分子的表达。结果与对照组相比,不同浓度的ADMA可显著抑制HU-VECs产生NO和粘附的能力、增强细胞表面ICAM-1和VCAM-1的表达。结论ADMA可抑制体外培养的HUVECs粘附功能。     

Preservation of arm veins for arterial reconstruction.

The results of surgery for lower extremity salvage have improved steadily over the past decade. One of the principles accounting for this advance is the preferential use of autogenous veins for peripheral bypass surgery. Nonautogenous and prosthetic grafts to the infrageniculate (below knee) level have patency rates significantly lower than autogenous bypasses. Currently, the technical limits of bypass surgery often depend upon the availability of adequate venous conduits. The saphenous vein has been the conduit of choice for distal arterial bypasses. However, some patients lack saphenous veins as a result of previous vein harvesting for coronary or other arterial surgery, phlebitis, variations in venous anatomy, previous vein stripping, or other conditions. In these patients, arm veins (cephalic and basilic) have been used successfully for limb salvage. There are several requirements for the successful use of arm veins. These include a detailed knowledge of the anatomy of the cephalic and basilic veins, education of patients and health care professionals, nursing protocols to preserve arm veins, and the training of surgical nurses in the demanding technical maneuvers for arm vein implantation. This paper will address these subjects.     

Mechanisms of beta-adrenergic receptor-mediated venodilation in humans

OBJECTIVES: Recent studies suggest that stimulation of beta-adrenergic receptors results in both endothelium-dependent and endothelium-independent venodilation, but results of former studies are inconsistent. This study was designed to elucidate the underlying mechanisms of isoproterenol (INN, isoprenaline)-induced venodilation by investigation of dorsal hand vein responses. METHODS: In phenylephrine-constricted veins, isoproterenol (2-514 ng/min) was infused with and without oral pretreatment with 1 g acetylsalicylic acid (n = 7) or 5 mg of the selective beta(1)-adrenergic receptor antagonist bisoprolol (n = 7). In addition, isoproterenol was coinfused with the nitric oxide inhibitor N(G)-monomethyl-l-arginine (l-NMMA) (6.3 micromol/min [n = 6]), with selective blockers of calcium (Ca(++))-dependent potassium (K(+)) channels (tetraethylammonium, 300 microg/min [n = 6]) and adenosine triphosphate (ATP)-sensitive K(+) channels (glyburide [INN, glibenclamide], 20 microg/min [n = 6]) or with the cyclic guanosine monophosphate inhibitor methylene blue (13 microg/min [n = 6]). Finally, L-NMMA was coinfused with potassium chloride (20 mmol/L) to inhibit hyperpolarization (n = 6). RESULTS: Isoproterenol induced dose-dependent venodilation to 67.4% +/- 6.8%. Oral pretreatment with bisoprolol (P =.340) or acetylsalicylic acid (P =.760) did not affect isoproterenol-induced venodilation. Coinfusion of isoproterenol and L-NMMA relaxed the veins to the same extent as in the presence of isoproterenol alone. Neither inhibition of ATP-sensitive K(+) channels (P =.196) nor blockade of Ca(++)-dependent K(+) channels (P =.640) modulated isoproterenol-induced venodilation. In contrast, methylene blue reduced the maximum response to isoproterenol by about one third (68.5% +/- 4.3% versus 41.7% +/- 5.5%, P =.001). Infusion of L-NMMA alone raised vein size to 38.8% +/- 6.5%, yielding an L-NMMA-sensitive increase of 20% (P =.001), which was antagonized by coinfusion of potassium chloride to 17.1% +/- 6.7% (P =.02). CONCLUSIONS: Isoproterenol dilates human hand veins exclusively via beta(2)-adrenergic receptors without involvement of endothelium-derived epoprostenol. Although a contribution of endothelium-derived nitric oxide appears unlikely, the venodilating effect of L-NMMA could have obscured the nitric oxide component of isoproterenol. beta(2)-Adrenergic receptor-mediated dilation is mediated in part by cyclic guanosine monophosphate-dependent mechanisms, whereas ATP- and Ca(++)-dependent K(+) channels are not involved, excluding a significant contribution of smooth muscle cell hyperpolarization. In addition, high concentrations of the nitric oxide synthase blocker L-NMMA dilate human hand veins via activation of endothelium-derived hyperpolarizing factors.     

Heparin-induced vasodilation in human hand veins.

OBJECTIVE: To investigate whether heparin produces vasodilation in human veins and to explore the underlying mechanisms. METHODS: Eleven healthy volunteers were studied with the dorsal hand vein compliance technique. Dose-response curves to heparin and enoxaparin were generated. Dose-response curves to heparin were also constructed before and after heparin was infused with the nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine (L-NMMA) or combined histamine H1- and H2-receptor blockade. RESULTS: Heparin but not enoxaparin caused significant dose-dependent relaxation with an average apparent maximal response (at an infusion rate of 20 IU/min) of 47% +/- 23%. L-NMMA attenuated heparin-induced relaxation (P < .001). The combination of H1-and H2-receptor antagonists attenuated heparin-induced relaxation to a lesser extent (P < .05). Heparin-induced relaxation decreased by 52%, 73%, and 35% in the presence of L-NMMA, indomethacin (INN, indometacin) plus L-NMMA, and combined H1- and H2-receptor blockade, respectively. CONCLUSION: Heparin is an endothelium-dependent venodilator in humans. The mechanism of heparin-induced relaxation involves an increased availability of nitric oxide, possibly partially related to local release of histamine.     

过氧化物酶增殖物激活受体α激动剂降低高糖诱导的黏附因子的表达

目的探讨过氧化物酶增殖物激活受体(PPAR)α激动剂对高糖条件下人血管内皮细胞细胞间黏附因子-1(ICAM-1)和血管黏附因子-1(VCAM-1)表达的影响及相关机制。方法体外培养人脐静脉内皮细胞和HL-60细胞,酶联免疫吸附试验(ELISA)、HL-60细胞黏附试验及逆转录-聚合酶链反应(RT-PCR)方法检测ICAM-1和VCAM-1的表达,Western blotting和共聚焦显微镜方法探讨NF-κB通路IκB、磷酸化-IκB蛋白水平及p65亚基的移位,流式细胞仪和共聚焦显微镜方法检测细胞内活性氧离子(ROS)水平,化学发光法测定烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶的活性。结果 (1)高糖(33 mmol/L)干预24 h能够显著增加内皮细胞ICAM-1和VCAM-1的表达;(2)PPARα激动剂非诺贝特、NF-κB抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)和NADPH氧化酶抑制剂二联苯碘(DPI)显著抑制高糖诱导的ICAM-1和VCAM-1的表达;(3)高糖能够诱导内皮细胞IκBα的降解、磷酸化-IκBα蛋白水平的增加;另外,高糖可以显著增加内皮细胞NADPH氧化酶活性和细胞内ROS水平;非诺贝特则呈浓度依赖性的逆转高糖引起的上述效应。结论 PPARα激动剂非诺贝特通过抑制NF-κB通路和NADPH氧化酶的激活降低高糖诱导的人血管内皮细胞炎症因子ICAM-1和VCAM-1的表达。     

Nicotine impairs endothelium-dependent dilatation in human veins in vivo

BACKGROUND: Cigarette smoking is associated with impaired endothelium-dependent dilatation in human veins and arteries. An in vivo study in animals suggests that nicotine may contribute to this abnormality. We tested the hypothesis that local administration of nicotine at a dose reproducing the plasma concentration observed during smoking would impair endothelium-dependent vasodilatation in human veins in vivo. METHODS: We studied 11 healthy nonsmokers with the dorsal hand vein compliance technique. After 70% to 80% preconstriction with phenylephrine, endothelium-dependent venous relaxation was assessed by infusion of bradykinin (1 to 278 ng/min), a potent vasodilator acting primarily in this model through endothelial release of nitric oxide and prostanoids. Sodium nitroprusside (0.0001 to 3166 ng/min) was used to test endothelium-independent relaxation. Dose-response curves were constructed before and during nicotine coinfusion at a rate of 40 ng/min, reproducing a plasma concentration of 15 ng/mL. RESULTS: After a 10-minute preinfusion, nicotine administration was associated with a loss in sensitivity to bradykinin (P < .001). After 30 and 60 minutes of preinfusion with nicotine, the venorelaxant effect of bradykinin was further reduced (P < .001). A similar inhibition of the response to bradykinin by nicotine persisted in the presence of indomethacin (INN, indomethacin). Coinfusion of nicotine did not attenuate sodium nitroprusside-induced venodiiation. CONCLUSION: The results show that acute local exposure to nicotine in vivo is associated with an impaired response to endothelium-derived nitric oxide in human veins. This finding may provide further insight into the pathophysiology of smoking-induced endothelial dysfunction.     

Plasma soluble adhesion molecules and endothelium-dependent vasodilation in early human atherosclerosis

Levels of soluble cellular adhesion molecules are increased in patients with atherosclerosis, and have been found to predict coronary heart disease. Therefore these molecules have been suggested to represent laboratory markers for inflammation and activation of endothelial cells. Impaired endothelium-dependent vasodilation has been demonstrated to be an early marker of atherosclerosis. We hypothesized that soluble adhesion molecules are related to impaired endothelium-dependent vasodilation and may serve as an early marker of atherosclerosis. Patients (n=52) with moderate and uncomplicated hypercholesterolaemia [low-density lipoprotein (LDL)-cholesterol 4.89+/-1.26 mmol/l] were compared with healthy controls (n=43; LDL-cholesterol 2.44+/-0.79 mmol/l). Endothelium-dependent vasodilation of the forearm vasculature was assessed by intra-arterial infusion of acetylcholine (12 and 48 microg/min). Forearm blood flow was measured by venous occlusion plethysmography. Plasma concentrations of the soluble forms of ICAM-1 (intercellular cell adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1) and E-selectin were measured by ELISA. Hypercholesterolaemic patients had impaired endothelium-dependent vasodilation in comparison with healthy controls (forearm blood flow after 48 microg/min acetylcholine: 21.3+/-10.6 and 30.4+/-16.3 ml. min(-1).100 ml(-1) respectively; P=0.002). Plasma concentrations of soluble adhesion molecules were not different between hypercholesterolaemic patients and controls (ICAM-1, 196+/-56 and 180+/-38 ng/ml respectively; VCAM-1, 431+/-137 and 405+/-65 ng/ml respectively; E-selectin, 39+/-17 and 37+/-12 ng/ml respectively). Moreover, levels of soluble adhesion molecules were not correlated with endothelium-dependent vasodilation. Thus, in hypercholesterolaemic patients without clinical atherosclerosis, levels of soluble adhesion molecules were not elevated in comparison with healthy controls. In addition, these markers of endothelial inflammation were not related to impaired endothelium-dependent vasodilation. Our data indicate that measurement of levels of soluble adhesion molecules cannot replace assessment of endothelium-dependent vasodilation in detection of early hypercholesterolaemic atherosclerosis.     

Ultrasonographic measurement of saphenous vein diameter compared to CEAP classification in patients with varicose veins

Introduction and ObjectiveUltrasound of the saphenous vein and measurement of the vein diameter may have a role in determining the severity of varicose veins. This study aimed to compare the saphenous vein diameter with the CEAP classification, as the reference standard in determining the severity of chronic venous diseases, in patients with lower limbs varicose veins free from saphenous vein reflux.MethodsIn this cross-sectional study, 100 patients with lower limbs varicose veins (saphenous vein) and free from saphenous vein reflux were enrolled. Demographic data (age, gender, body mass index (BMI)) were collected using a checklist. The severity of varicose veins was determined using the standard CEAP classification. The saphenous vein diameter was measured using ultrasonography.ResultsMean age of the patients was 43 years and there were 68 female patients. According to the CEAP classification, 13 patients had no varicose veins (CEAP class C0). However, 87 patients had varicose veins (65 patients with class C1, one patient with class C2, and 21 patients with class C3). Mean saphenous vein diameter in the whole sample was 6.7 mm. There was no significant relationship between the severity of varicose veins determined by CEAP classification and mean saphenous vein diameter measured by ultrasound. Mean saphenous vein diameter in C0, C1, C2, and C3 groups were respectively 1.7 mm, 6.7 mm, 8 mm, and 8.7 mm (P= 0.71). On the other hand, mean saphenous vein diameter was higher significantly in those with higher body mass index (BMI) and among older patients.ConclusionThe results of this study showed that saphenous vein diameter did not differ significantly between CEAP C0 through C4 classes. However, the severity of varicose vein was more prominent in older patients and those with higher BMI.     

Correlation of preoperative ankle-brachial index and pulse volume recording with impaired saphenous vein incisional wound healing post coronary artery bypass surgery.

Patients undergoing coronary artery bypass surgery have vascular disease and, subsequently, the risk for impaired healing of their saphenous vein graft site. The purpose of this study was to identify the correlation of the preoperative ankle-brachial index (ABI) and pulse volume recording (PVR) with impaired saphenous vein incisional wound healing post coronary artery bypass grafting. A prospective, correlational research design was used to study 271 male and female adults undergoing coronary artery bypass surgery in which the saphenous vein was used for grafting. Arterial insufficiency was assessed preoperatively using patient history, physical examination, ABI, and PVR. Wound status was assessed postoperatively using the validated ASEPSIS tool for inpatients. A modified ASEPSIS tool, the Wound Healing Self Score, was used for telephone follow-up post discharge. Abnormal ABI and PVR measurements were positively correlated with impaired saphenous vein incisional wound healing (r = 0.72, P < .0001). Both tests also independently predicted impaired healing. Incisional infection correlated with impaired healing (P < .0001). Other clinical variables, including diabetes, hypertension, venous disease, and alcohol and cigarette use, were not found to be statistically significant independent predictors of impaired healing. Routine histories and physical examinations alone are insufficient in predicting risk for impaired saphenous vein incisional wound healing. The addition of noninvasive screening for the presence of arterial insufficiency before coronary artery bypass grafting using ABI and PVR tests is one method of predicting the likelihood of impaired healing.     

Dilator actions of arginine in human peripheral vasculature.

1. L-Arginine is the physiological precursor for the formation of endothelium-derived nitric oxide. The synthesis of nitric oxide is stereospecific: D-arginine is not a substrate for nitric oxide synthase. It is possible that the provision of excess L-arginine substrate might increase the vascular synthesis of nitric oxide. We have examined this possibility by studying the effects of local infusion of L- and D-arginine in the forearm resistance bed and the superficial dorsal hand veins of healthy subjects. 2. Drugs were either infused locally into a vein on the back of the hand and then the vein diameter was measured using a linear displacement technique, or into the brachial artery and then the forearm blood flow was measured by venous occlusion plethysmography. 3. In the superficial hand veins, L- and D-arginine free base and L- and D-arginine hydrochloride (all four preparations at a dose of 5 mumol/min) all caused a significant increase in venous diameter. The responses of the L- and D-enantiomers did not differ significantly from one another. 4. In the forearm resistance bed, L- and D-arginine free base and L- and D-arginine hydrochloride were without effect at doses of 10 and 40 mumol/min. However, at doses of 160 mumol/min all three preparations of arginine caused a significant increase in forearm blood flow compared with control values. The responses to the three preparations of arginine did not differ significantly from one another. 5. These results show that arginine in high dose is a vasodilator in both human resistance vessels and superficial veins in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Superoxide Anion Generation, Superoxide Dismutase Activity, and Nitric Oxide Release in Human Internal Mammary Artery and Saphenous Vein Segments

BACKGROUND: Internal mammary artery (IMA) as conduit for a coronary artery bypass graft (CABG) stays patent longer and more often than saphenous vein (SV). However, the precise differences in the biology of IMA and SV are unclear. METHODS AND RESULTS: To examine inherent difference in superoxide anion, superoxide dismutase (SOD) and nitric oxide (NO) formation in IMA and SV as a basis for differences in patency rates, we measured these parameters in vascular segments of patients undergoing CABG. Superoxide anion generation was measured by lucigenin chemiluminescence and reduction of cytochrome c, SOD by inhibition of pyrogallol auto-oxidation, and No as nitrite/nitrate fluorometrically using 2-3-diaminonaphthalene as a probe. Generation of superoxide anion, SOD activity, and No formation were all greater in the IMA than in the SV segments (IMA:SV = 2.6:1, 2.9:1, 1, and 3.0:1, respectively, all P <.010. There was a positive correlation between superoxide anion generation and SOD activity (r = 0.65, P <.05; r = 0.70, P <.05 in IMA and SV, respectively) and NO release (r = 0.68, P <.05; r = 0.75, P <.03 in IMA and SV, respectively). Western blot analysis showed no differences in SOD and NO synthase protein expression in IMA and SV segment homogenates. To examine whether greater superoxide anion generation, SOD activity, and NO formation are unique to IMA, we studied pulmonary artery (PA) and pulmonary vein (PV) segments taken from patients undergoing lung resection. Superoxide anion generation, SOD activity, and NO formation were also found to be greater in PA than in PV segments. CONCLUSIONS: Inherently greater superoxide anion generation and subsequently increased formation of SOD and NO release in IMA (vs SV) may be a factor in the greater patency of the former as CABG conduit. Because both IMA and PA are exposed to pulsatile stretch and cary blood at higher pressure than the SV and PV, it is likely that these 2 factorsd account for the observed differences.     

下肢股腘动脉搭桥术中应用复合移植物6例报告

目的：为寻求一种有效的长距离膝下移植物来治疗下肢动脉长段阻塞或动脉旁路 远端动脉阻塞,方法：自１９９５年２月～１９９９年２月采用复合移植物治疗下肢股Ｕｕｏ动脉硬化闭塞症共６例,包括（１）“直接式”吻合法;（２）“跳跃式”吻合法;（３）“连贯式”吻合法：即先做膝上股Ｇｕｏ动脉人造血管移植。再做人造血管－自体大隐静脉－膝下Ｇｕｏ动脉端侧吻合。结果：经术后３年随访,６例中４例症状消失,２例症状同术前,结论：当无法应用单一的大隐静脉或人造血管时,复合移植物对治疗下肢股瘤动脉长段闭塞,特别是病变累及膝下动脉时,是合适的血管代用品。     

Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells.

Accumulation of monocyte-derived foam cells in focal areas of the arterial intima is one of the key events in early atherogenesis. We have examined the effect of lysophosphatidylcholine (lyso-PC; lysolecithin), a major phospholipid component of atherogenic lipoproteins, on the expression of adhesion molecules for monocytes, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), in cultured human and rabbit arterial endothelial cells. Cultured rabbit aortic endothelial cells treated with lyso-PC showed increased mRNA and cell surface expression of VCAM-1 and ICAM-1, which was associated with increased adhesion of monocytes and monocyte-like cells (THP-1, U937). In cultured human iliac artery endothelial cells, lyso-PC similarly induced both VCAM-1 and ICAM-1, whereas in umbilical vein endothelial cells only ICAM-1 was up-regulated. In all endothelial cells examined, the effect of lyso-PC on E-selectin (endothelial-leukocyte adhesion molecule-1) expression was negligible, thus differentiating this stimulus from other endothelial activators, such as interleukin 1, tumor necrosis factor, or lipopolysaccharide. We conclude that lyso-PC can selectively induce VCAM-1 and ICAM-1 in arterial endothelial cells and that this action, in addition to its monocyte chemoattractant activity, may play an important role in monocyte recruitment into atherosclerotic lesions.     

Vascular effects of neurokinins in humans

Neurokinins (mainly substance P and neurokinin A) are released by sensitive nerve fibres. These fibres have been found in the vascular wall of arteries and veins of many vascular regions, particularly in nasal mucosa vessels, temporal and coronary arteries and saphenous veins. Substance P causes vascular relaxation by stimulating NK1 endothelial receptors. This relaxant effect is mediated, according to the vessels, by nitric oxide (NO), prostanoids or endothelium-dependent hyperpolarizing factor (EDHF). Capsa?cin, which induces the release of neurokinins, and neurokinin A can cause contractions of some vascular preparations, suggesting the existence of smooth muscle NK2 receptor associated with contraction. The vasodilatation induced by substance P injection appears reduced in patients with cardiovascular risk factors. The clinical development of specific neurokinin receptor antagonists may give the opportunity to specify the role of neurokinins in systemic vascular diseases. The results already obtained after repeated local applications of capsa?cin (to reduce local levels of neurokinins) in vasomotor rhinitis and urticaria suggest that the vascular effects of neurokinins may participate in the clinical expression of these diseases.     

Transdermal nicotine mimics the smoking-induced endothelial dysfunction

BACKGROUND: Cigarette smoking is a major risk factor for coronary artery disease and causes endothelial dysfunction, perhaps by decreasing the availability of nitric oxide availability in arteries and veins. Nicotine in cigarette smoke may be responsible for this impaired endothelial response. METHODS: We studied nine healthy nonsmokers and 12 healthy mild to moderate smokers by use of the dorsal hand vein compliance technique. Dose-response curves to bradykinin and sodium nitroprusside were obtained to test the endothelium-dependent and endothelium-independent vasorelaxation before and during the use of a nicotine (21 mg) patch. Mean arterial blood pressure and heart rate were measured beat-to-beat during the 4-hour study and serial blood samples were drawn to assay plasma thromboxane B2 levels. RESULTS: Transdermal nicotine reduced the venous responsiveness to bradykinin in nonsmokers (Emax = 88.0% +/- 17.9% and 54.3% +/- 14.9%, respectively, before and after the nicotine patch; P < .05); the latter response was similar to that in smokers (Emax = 56.3% +/- 16.6%). Sodium nitroprusside-induced venodilation was unaltered. Mean arterial blood pressure increased in both smokers and nonsmokers. Transdermal nicotine increased the plasma thromboxane B2 concentrations only among nonsmokers. CONCLUSION: These findings indicate that nicotine can have a major role in the impaired endothelial function in smokers. The results probably also reflect what occurs in arterial beds because the nicotine patches increased the mean arterial blood pressure in both smokers and nonsmokers.     

激光联合大隐静脉高位结扎术治疗原发性下肢静脉曲张的疗效

目的探讨激光联合大隐静脉高位结扎术治疗原发性下肢静脉曲张的疗效。方法将291例原发性下肢静脉曲张患者按随机数字表法分成2组：治疗组146例,采用激光联合大隐静脉高位结扎术治疗;对照组145例,单纯采用激光治疗。通过全自动血液流变快测仪测定2组全血黏度低切（10 s-1）、中切（30 s-1）、高切（100 s-1）、血浆黏度（100 s-1）、红细胞压积、纤维蛋白原（g.L-1）。彩色多普勒超声诊断仪检测2组患者收缩期最大血流速度（Vmax）、舒张期最低血流速度（Vmin）、平均血流速度（TAP）、血流时间速度积分面积（VTI）、血管内径、每分血流量,并观察2组的疗效。结果治疗组总有效率为95.2%,对照组有效率为87.6%,2组比较差异无统计学意义（P〉0.05）。血液流变学检查：治疗组术后1周的全血黏度低切、中切、高切,血浆粘度、红细胞压积、纤维蛋白原与术后1年比较差异均无统计学意义（均P〉0.05）;对照组术后1周的全血黏度低切、中切、高切,血浆粘度、红细胞压积、纤维蛋白原与术后1年比较差异均有统计学意义（P〈0.05或P〈0.01）。血流动力学检查：治疗组股总静脉、股浅静脉、股深静脉、腘静脉术后1周、1年血流动力学检查结果比较差异均无统计学意义（均P〉0.05）。对照组股总静脉Vmin术后1周、1年,血流量术后1年、股浅静脉内径（nm）术后1年,股深静脉内径、血流量术后1年,腘静脉TAP、血流量术后1周、1年与参考值比较差异有统计学意义（P〈0.05或P〈0.01）。结论激光联合大隐静脉高位结扎术治疗原发性下肢静脉曲张手术方法安全、有效,疗效优于单纯激光治疗。     

Effect of inhibition of nitric oxide synthase on dynamic cerebral autoregulation in humans

Cerebral blood flow is maintained constant over a range of cerebral perfusion pressures by cerebral autoregulation. Impaired cerebral autoregulation may be important in the pathogenesis of cerebral ischaemia. The mechanisms mediating normal cerebral autoregulation in humans are poorly understood. We used a recently described transcranial Doppler technique, which allows non-invasive measurement of dynamic cerebral autoregulation, to test the hypothesis that nitric oxide mediates cerebral autoregulation. The rate of rise of middle cerebral artery blood flow velocity, compared with that of arterial blood pressure, was determined following a stepwise fall in arterial blood pressure, in order to calculate an autoregulatory index. The effect of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on dynamic autoregulation was compared with that of noradrenaline titrated to result in a similar rise in blood pressure. Six healthy subjects were studied in each group. The mean (S.D.) change in autoregulatory index following noradrenaline at a similar pressor dose was significantly greater than the change following the L-NMMA bolus: 1. 1 (1.2) compared with -0.8 (0.8) for the left middle cerebral artery (P=0.002), and 1.1 (0.8) compared with -0.8 (0.8) for the right middle cerebral artery (P=0.002). There was no difference in the mean (S.D.) blood pressure increase resulting from the two agents: L-NMMA, 19.7 (7.4) mmHg; noradrenaline, 15.5 (4.8) mmHg (P=0.281). These results suggest that nitric oxide mediates at least part of the dynamic phase of cerebral autoregulation in humans. Reduced nitric oxide release may play a role in the impaired cerebral autoregulation seen in patients with, or at risk of, cerebral ischaemia.     

Multicenter radial artery patency study (RAPS). Study design

The use of an internal thoracic artery rather than a saphenous vein graft for left anterior descending coronary artery bypass is associated with improved long-term outcome. Hence, expanded use of arterial conduits for other coronary targets has been advocated. The radial artery possesses a number of anatomic features that are technically advantageous compared with other arterial conduits. This study will determine the relative patency of the radial artery compared to the saphenous vein for right and circumflex coronary bypass. Patients with graftable multivessel coronary disease and an estimated left ventricular ejection fraction >/= 35% undergoing nonemergent primary isolated coronary bypass surgery are eligible. The right and circumflex vessels must have high-grade lesions (>/= 70% diameter stenosis), with target segments of reasonable quality >/= 1.5 mm in diameter. Patients serve as their own controls. The radial artery is randomly allocated to bypass the right or circumflex territory and a saphenous vein is used for the nonradial site. An internal thoracic artery is used for the left anterior descending coronary artery in all cases. Randomization is stratified by center. The primary study endpoint is graft patency as determined by angiography, 8-12 months postoperatively. The relative patency of the radial artery compared with the saphenous vein will be determined using McNemar's test. A sample size of 464 patients will provide 80% power for a two-tailed test (alpha = 0.05) for a 40% relative reduction in the rate of distal anastomotic occlusion from 12% in the saphenous vein to 7.2% in the radial arteries assuming a 20% within-patient correlation. A single interim analysis will be performed following completion of 232 angiograms. To allow for lack of follow-up angiography in up to 20% of enrolled patients, we plan to randomize a total of 560 patients. It is also our intention to assess the long-term patency (5-10 years) of radial artery relative to saphenous vein grafts in follow-up studies. Three hundred patients were recruited from 12 Canadian, university-affiliated sites from November 1996 until February 1999, of which 128 patients have undergone follow-up angiography. Approximately 80% of those who have been followed for more than 1 year have undergone follow-up angiography. This trial will determine the 8-12 month patency of the radial artery relative to the saphenous vein for non-left anterior descending coronary bypass using a novel study design which helps control for potential bias from individual patient and vessel factors. Positive results would support the use of the radial artery in particular, and multiple arterial grafts in general.