Effect of antioxidant vitamin supplementation on endothelial function in type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

Controversy exists among trials assessing whether prolonged antioxidant vitamin supplementation improves endothelial function in type 2 diabetes mellitus (T2DM) subjects. The aim of this study was to systematically review and quantify the effect of antioxidant vitamin supplementation on endothelial function in T2DM subjects. MEDLINE, Cochrane, Scopus and Web of Science were searched up to February 2013 for randomized controlled trials assessing the effect of antioxidant vitamin E and/or C supplementation on endothelial function in T2DM subjects. Ten randomized controlled trials comparing antioxidant vitamin-supplemented and control groups (overall n = 296) met the inclusion criteria. Post-intervention standardized mean difference (SMD) in endothelial function did not reach statistical significance between groups (0.35; 95% confidence interval = -0.17, 0.88; P = 0.18). In subgroup analysis, post-intervention endothelial function was significantly improved by antioxidant vitamin supplementation in T2DM subgroups with body mass index (BMI) ≤ 29.45 kg m(-2) (SMD = 1.02; P < 0.05), but not in T2DM subgroups with BMI > 29.45 kg m(-2) (SMD = -0.07; P = 0.70). In meta-regression, an inverse association was found between BMI and post-intervention SMD in endothelial function (B = -0.024, P = 0.02). Prolonged antioxidant vitamin E and/or C supplementation could be effective to improve endothelial function in non-obese T2DM subjects.

The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes.

AIMS/HYPOTHESIS: Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. We studied the role played by total adiponectin and by the bioactive high-molecular-weight (HMW) oligomeric complexes of adiponectin in vascular function in offspring whose parents both had type 2 diabetes, a population at high risk of diabetes and atherosclerosis. METHODS: Total and %HMW adiponectin, the cytokines C-reactive protein, interleukin-6 and plasminogen activator inhibitor-1 (PAI-1), as well as lipid profiles were assayed in 19 offspring, each with two type 2 diabetic parents. Subjects underwent OGTTs and IVGTTs. Endothelium-dependent vasodilation (EDV) was assessed by brachial artery ultrasonography. RESULTS: There was a significant relationship between %HMW and total adiponectin levels (r=0.72, p=0.001). Despite an expected strong positive correlation between HDL-cholesterol and adiponectin levels (r=0.52, p=0.04), as well as HDL-cholesterol and EDV (r=0.56, p<0.02), there was no significant relationship between either total adiponectin or % HMW adiponectin and EDV. Adiponectin was inversely associated with PAI-1 (r=0.50, p=0.05), but did not correlate with the inflammatory markers C-reactive protein or interleukin-6. CONCLUSIONS/INTERPRETATION: In offspring of diabetic parents, a population at high risk of diabetes and atherosclerotic disease, there is no relationship between total or %HMW adiponectin and endothelium-dependent vasodilation. However, low adiponectin was associated with impaired fibrinolysis as manifested by increased levels of plasminogen activator inhibitor-1.

Ictal asystole with convulsive syncope mimicking secondary generalisation: a depth electrode study.

Ictal bradycardia is rare and its localising value is debated. Bradyarrhythmias are, however, important because of their potential connection to sudden death and ability to affect clinical seizure manifestations. Cerebral hypoperfusion induces loss of consciousness, at times with myoclonic jerks, whose clinical differentiation from a generalised convulsive seizure may prove difficult. Two invasive and five surface monitored seizures recorded over two years in a 51 year old woman with post-traumatic epilepsy characterised by seizure-triggered asystole were analysed. All seven seizures showed left temporal onset. Both intracranially recorded events started in the left anterior hippocampus/amygdala, spreading to the contralateral hippocampus in 35 and 25 seconds. Within 10 seconds an electrocardiogram showed asystole lasting 21 and 28 seconds, associated with suppression of recorded cerebral electrical activity, except a polyspike suppression pattern remaining in the hippocampi. Clinically, the patient, concomitantly with the cerebral suppression, developed myoclonic twitches of the limbs. A dual chamber cardiac pacemaker was implanted; at 11 months follow up, the patient has experienced only infrequent partial seizures, with none involving falls or shaking. Left temporal lobe seizures produced convulsive syncope initiated by ictal asystole. These observations suggest that intertemporal spread is necessary, though not sufficient, to produce bradycardia and asystole. Furthermore, pacemakers may decrease seizure severity, as well as potentially protect against malignant bradyarrhythmias.

Radiation therapy impairs endothelium-dependent vasodilation in humans.

OBJECTIVES: The objective of this study was to test the hypothesis that external-beam radiation induces a chronic impairment of endothelium-dependent vasodilation. BACKGROUND: Radiation therapy is used commonly in the treatment of cancer and is associated with an increased incidence of adverse vascular events related to the field of radiation, including stroke and myocardial infarction. As endothelial injury is central to the pathogenesis of vascular diseases, we hypothesized that radiotherapy induces arterial endothelial dysfunction. METHODS: Sixteen women with unilateral breast cancer who underwent standard external-beam radiation therapy to the breast and axilla >3 years before enrollment and ten healthy women were studied. Vascular ultrasonography was used to image both the artery exposed to radiation and the contralateral artery. Flow-mediated, endothelium-dependent vasodilation and endothelium-independent vasodilation to nitroglycerin of both axillary arteries were measured. RESULTS: Endothelium-dependent vasodilation was significantly impaired in the irradiated axillary arteries compared with the contralateral, nonirradiated arteries (-0.4 +/- 0.4% vs. 3.2 +/- 0.8% p < 0.001) and also compared with control subjects' arteries (-0.4 +/- 0.4% vs. 2.5 +/- 0.6%, p < 0.001). In contrast, endothelium-independent vasodilation was greater in the arteries that received radiation compared with the contralateral arteries (3.8 +/- 0.5% vs. 2.0 +/- 0.4%, p < 0.05) and also compared with control arteries (3.8 +/- 0.5% vs. 2.5 +/- 0.4%, p < 0.05). CONCLUSIONS: External beam radiation therapy impairs endothelium-dependent vasodilation of conduit arteries, implicating a decrease in the bioavailability of nitric oxide. These abnormalities may contribute to the development of arterial occlusive disease and associated clinical events.

Relationship of clinical presentation and calcification of culprit coronary artery stenoses.

Coronary artery calcification is increased in the presence of atherosclerosis. However, there is great variability in the calcification of individual coronary stenoses, and the clinical significance of this finding remains unknown. We tested the hypothesis that culprit lesions associated with myocardial infarction or unstable angina are less calcified than are stenoses associated with stable angina. The study consisted of 78 patients who underwent intravascular ultrasound imaging of culprit stenoses after the placement of a stent. Seventeen patients presented with stable angina; 43, with unstable angina; and 18, with myocardial infarction. The extent of coronary calcification was measured by the angle of its arc and was quantified with a computer-based protractor. The arc of calcium was measured in the stented area at the point of maximal calcification and also as an average of the calcification found at proximal, middle, and distal stent segments. The maximal arc of calcium decreased progressively from patients with stable angina (91+/-10 degrees ) to those with unstable angina (59+/-8 degrees ) and to those with myocardial infarction (49+/-11 degrees, P=0.014). Similarly, the average arc of calcium was greatest (32+/-7 degrees ) in patients with stable angina, less (15+/-4 degrees ) in patients with unstable angina, and least (10+/-5 degrees ) in patients with acute myocardial infarction (P=0.014). These associations remained significant after adjustment for other factors that potentially affect arterial calcification. Acute coronary syndromes are associated with a relative lack of calcium in the culprit stenoses compared with stenoses of patients with stable angina. These findings have implications for the understanding of the biology of acute coronary syndromes as well as for the identification of coronary stenoses by methods that rely solely on the presence of calcium.

Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans.

BACKGROUND: Endothelium-dependent vasodilation is impaired in patients with insulin-dependent and non-insulin-dependent diabetes mellitus and restored by vitamin C administration, implicating a causative role for oxidant stress. Hyperglycemia per se attenuates endothelium-dependent vasodilation in healthy subjects. Accordingly, this study investigated whether impaired endothelium-dependent vasodilation caused by hyperglycemia in nondiabetic humans is restored by administration of the antioxidant vitamin C. METHODS AND RESULTS: Endothelium-dependent vasodilation was measured by incremental brachial artery administration of methacholine chloride (0.3 to 10 microg/min) during euglycemia, after 6 hours of hyperglycemia (300 mg/dL) created by dextrose (50%) intra-arterial infusion, and with coadministration of vitamin C (24 mg/min) during hyperglycemia. Endothelium-dependent vasodilation was significantly diminished by hyperglycemia (P:=0.02 by ANOVA) and restored by vitamin C (P:=0.04). In contrast, endothelium-dependent vasodilation was not affected by equimolar infusions of mannitol, with and without vitamin C coinfusion (P:=NS). Endothelium-independent vasodilation was measured by incremental infusion of verapamil chloride (10 to 300 microg/min) without and with coadministration of N:(G)-monomethyl-L-arginine (L-NMMA). In the absence of L-NMMA, endothelium-independent vasodilation was not significantly altered during hyperglycemia (P:=NS) but was augmented by vitamin C (P:=0.04). The coadministration of L-NMMA eliminated the vitamin C-related augmentation in verapamil-mediated vasodilation. CONCLUSIONS: Vitamin C administration restores endothelium-dependent vasodilation impaired by acute hyperglycemia in healthy humans in vivo. These findings suggest that hyperglycemia may contribute in part to impaired vascular function through production of superoxide anion.

Therapeutic thrombin injection of pseudoaneurysms: a multicenter experience.

The standard non-invasive treatment of pseudoaneurysms has been ultrasound-guided compression (UGC). Problems with UGC include pain at the site of compression, long compression times and incomplete closure. Each of these difficulties is exacerbated with large pseudoaneurysms. Recently, ultrasound-guided injection of pseudoaneurysms with thrombin has gained popularity. The goal of this study was to report a multicenter registry using this technique and in so doing detail the clinical utility and safety of this emerging procedure. The medical records of all patients diagnosed with pseudoaneurysm in the vascular laboratory who underwent thrombin injection over the past year were reviewed for patient characteristics and clinical outcome. There were 91 patients (55 male) with a mean age of 69 years. Three patients also had an arteriovenous fistula. The majority of patients were receiving one or more antiplatelet agents and/or anticoagulants. All patients underwent pseudoaneurysm injection with bovine thrombin. The mean aneurysm diameter was 3.3 cm, with a range of 1.5-6.3 cm. Successful thrombosis of the pseudoaneurysm was achieved in 89/91 (98%) of cases. Anticoagulation with heparin was used in one of the unsuccessful cases. In two cases, UGC was used to close a small active region that did not completely thrombose after thrombin injection. There were two patients who had recurrence of pseudoaneurysm the day after successful injection and thrombosis of the pseudoaneurysm. There were no local complications after injection; however, one patient suffered a pulmonary embolus that was thought to be unrelated to the procedure. In conclusion, thrombin injection for the treatment of pseudoaneurysms is safe and effective, even in patients receiving anticoagulation. This procedure should be considered as the initial therapeutic approach for peripheral pseudoaneurysms.

Successful anticoagulation with hirudin in a patient with mesenteric venous thrombosis and multiple coagulation abnormalities.

A case of multiple thrombotic diatheses discovered in the setting of mesenteric venous infarction is discussed. The patient had deficiencies of protein C, protein S, antithrombin III; was heterozygous for factor V Leiden; and had polycythemia vera. Adequate anticoagulation could not be established with heparin administration and hirudin was used. The diagnosis of mesenteric venous infarction, thrombotic tendency of multiple coagulation diatheses, and use of hirudin are discussed.