Rita Lombardini

WHOLE-BLOOD FILTERABILITY IN SUDDEN DEAFNESS

Sixteen patients with sudden deafness (SD), diagnosed on the basis of a battery of audiometric tests, but with no other medical or surgical pathology requiring drug treatment, underwent monitoring of their hemorheological profiles to see whether disturbances in the microcirculation could be linked to SD. Plasma viscosity, the filterabilities, (using a low‐shear positive pressure system) through 5‐μm‐diam‐eter pore Nuclepore filters, of whole blood and red and unfractionated white cells were monitored in 16 SD patients and 32 controls matched for age, sex and socioeconomic status. Whole blood filterability and the filterability of the red blood cells were significantly impaired in the SD patients, which suggests that alterations in the microcirculation are linked, in some way, to sudden deafness.

Use of pentoxifylline as an inhibitor of free radical generation in peripheral vascular disease : results of a double-blind placebo-controlled study

SummaryThe effects of an infusion of pentoxifylline 1 g as an inhibitor of free radical generation have been determined in a double-blind placebo-controlled study. Leucocyte-derived free radical generation (by the superoxide dismutase-inhibitable reduction of ferricytochrome), the release of reactive oxygen metabolites (as plasma oxidant activity), unfractionated leucocyte and erythrocyte filterability rates (using a constant-flow positive-pressure system), plasma viscosity, and plasma fibrinogen concentration have been measured in two matched groups of 10 patients with Stage II peripheral vascular disease, before and after treatment. Transcutaneous oxygen pressure (PtcO2) during treadmill exercise to stress leg circulation was also measured.Leucocyte-derived free radicals were generated during peripheral ischaemia. Pentoxifylline inhibited their generation, blocked the release of reactive oxygen metabolites, and reduced impairment of the filterability rate of unfractionated leucocytes.The improvements were accompanied by significant shortening of the half-time of recovery of transcutaneous oxygen pressure, indicating that ischaemic damage had been contained.

Mechanisms of high-density lipoprotein cholesterol effects on the endothelial function in hyperlipemia

High-density lipoprotein-cholesterol (HDL-c) has a favorable influence on the endothelial function, but the mechanisms of this protective action are not fully understood. We studied lipid parameters, soluble adhesion molecules (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule [ICAM-1], E-selectin) oxidized low-density lipoproteins (LDL), and brachial-artery flow-mediated vasodilation (FMV) in 184 hyperlipemic patients (90 men, age 54 +/- 10 years, waist/hip circumference ratio 0.89 +/- 0.07, LDL-cholesterol [LDL-c] 4.9 +/- 1.3 mmol/L, triglycerides 1.8 +/- 0.9 mmol/L, HDL-c 1.3 +/- 0.5 mmol/L) after excluding those with current smoking, diabetes, hypertension, and vascular diseases. Patients were divided into 2 groups on the basis of HDL-c levels: < 1.03 mmol/L (n = 53) v >or= 1.03 mmol/L (n = 131). Patients with low HDL-c showed significantly lower LDL-c (P <.05), higher triglycerides (P <.001), higher body mass index (P <.02), lower FMV (3.7% +/- 2.0% v 4.9% +/- 3.4%, P <.002), higher VCAM-1 (1,195 +/- 395 ng/mL v 984 +/- 303 ng/mL, P <.01), and higher ICAM-1 (406 +/- 78 ng/mL v 364 +/- 68 ng/mL, P <.01). E-selectin and oxidized LDL showed no significant differences. In a multivariate age, oxidized LDL and brachial artery diameter predicted a lower FMV, while HDL-c was an independent predictor of a greater FMV (P =.003). Increasing levels of VCAM-1 and ICAM-1 were predicted by lower HDL-c, while higher oxidized LDL predicted higher VCAM-1 (P <.05). Our data suggest that in hyperlipemic subjects free of cardiovascular disease low HDL-c negatively modulates endothelial function through a lack of oxidation inhibition and a concomitant overexpression of adhesion molecules.

Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia.

Background:  Fasting and post‐prandial hypertriglyceridemia have been associated with endothelial dysfunction.

Prognostic impact of low‐shear whole blood viscosity in hypertensive men

Background  The role of blood viscosity as a marker for discriminating cardiovascular risk in essential hypertension remains uncertain. The aim of this study was to assess whether whole blood viscosity (WBV) could be useful in assessing cardiovascular risk in men with a first diagnosis of hypertension.

Prostaglandin E1 improves endothelial function in critical limb ischemia.

Prostaglandin E1 (PGE1) may relieve rest pain and heal ulcers in critical limb ischemia, but its mechanism of action is still incompletely understood. To investigate the effects of PGE1 treatment on endothelial function evaluated as brachial artery flow-mediated vasodilation (FMV) and on soluble adhesion molecule plasma levels (vascular adhesion molecule-1 [sVCAM-1] and intercellular adhesion molecule-1 [sICAM-1]), 12 patients with critical limb ischemia were treated with daily PGE1 IV infusion (alprostadil 60 &mgr;g) for 2 weeks. FMV and plasma sICAM-1 and sVCAM-1 concentrations were determined at baseline, after the first infusion, and after 1 and 2 weeks. Compared with 30 healthy control subjects, patients had higher baseline sVCAM-1 (2.402 ± 296 ng/ml vs 972 ± 117 ng/ml) and sICAM-1 levels (464 ± 51 ng/ml vs 206 ± 37 ng/ml, both p < 0.05) and lower FMV (1.0 ± 1.1% vs 5.6 ± 1.6%, p < 0.05). sICAM-1 concentration progressively decreased with treatment (from 464 ± 51 ng/ml to 326 ± 56 ng/ml, 288 ± 42 ng/ml, and 279 ± 44 ng/ml after the first dose and, respectively, after 1 and 2 weeks; all p < 0.05). sVCAM-1 showed a reduction after 2 weeks (from 2.402 ± 296 ng/ml to 1.916 ± 176 ng/ml; p < 0.05). FMV improved after 1 and 2 weeks (from 1.0 ± 1.1% to 3.1 ± 0.6% and 5.2 ± 2.1%, both p < 0.05). In conclusion, treatment with PGE1 determines a significant improvement in endothelial function in patients with critical limb ischemia.

Efficacy of Low-Molecular-Weight Heparin in the Management of Intermittent Claudication

Treating chronic arterial occlu sive disease with heparin is contro versial because of the risks associated with long-term anticoagulant ther apy. Low molecular weight (LMW) heparin (mw about 5000 Dalton), which selectively inhibits the Xa fac tor with minimal risk of hemorrhage, seems to offer new possibilities in the prevention and treatment of both ve nous and acute arterial thromboem bolism. Therefore, 44 patients with inter mittent claudication were recruited to a randomized, double-blind, con trolled study. Twenty-two were treated for six months with a single daily subcutaneous dose (15,000 UaXa) of LMW heparin and 22 with placebo administered in the same way over the same period of time. After six months, LMW heparin treatment not only improved walking capacity (by lengthening the pain- free walking time by 25 %) but also significantly modified the hemor rheologic pattern (by reducing fibrin ogen concentrations and whole blood viscosity at low shear rates). LMW heparin also exerted an anti thrombotic and profibrinolytic effect by significantly increasing both the anti-Xa factor and plasminogen ac tivity without markedly modifying activated partial thromboplastin time ( + 20 %). No LMW heparin- treated patient hemorrhaged or re ported other noteworthy side effects. These results suggest LMW hepa rin might be a useful drug in the long- term treatment of chronic arterial occlusive disease of the limbs.

Effect of Oral Administration of Sulodexide on Fibrinolysis and Plasma Viscosity: A Pilot Study

SummaryThe purpose of this pilot study was to examine the effects of a new enteric-coated formulation of sulodexide, a glycosaminoglycan extracted from mammalian intestine, on blood, plasma and serum viscosity, and fibrinolysis in patients with plasma hyperviscosity. Six outpatients with plasma viscosity exceeding 1.40cP were administered oral sulodexide 100mg once daily for 7 days. On days 1 and 7 whole blood and plasma viscosity were measured before administration of sulodexide and 2, 4 and 8 hours after drug administration; at the same time functional and antigenic PAI (plasminogen activator inhibitor) and functional and antigenic tPA (tissue plasminogen activator) were evaluated to investigate the fibrinolytic balance of patients.The results demonstrated a marked reduction in plasma viscosity, which was observed 2 to 4 hours after the first dose of sulodexide and was even more marked on the seventh day, while whole blood and serum viscosities dropped only slightly after 7 days of sulodexide treatment. Sulodexide also induced a marked decrease in functional and antigenic PAI, and an increase in functional tPA, while no changes were observed in antigenic tPA.

The use of osteopathic manipulative treatment as adjuvant therapy in patients with peripheral arterial disease

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis associated with impaired endothelial function and intermittent claudication is the hallmark symptom. Hypothesizing that osteopathic manipulative treatment (OMT) may represent a non-pharmacological therapeutic option in PAD, we examined endothelial function and lifestyle modifications in 15 intermittent claudication patients receiving osteopathic treatment (OMT group) and 15 intermittent claudication patients matched for age, sex and medical treatment (control group). Compared to the control group, the OMT group had a significant increase in brachial flow-mediated vasodilation, ankle/brachial pressure index, treadmill testing and physical health component of life quality (all p<0.05) from the beginning to the end of the study. At univariate analysis in the OMT group there was a negative correlation between changes in brachial flow-mediated vasodilation and IL-6 levels (r=-0.30; p=0.04) and a positive one between claudication pain time and physical function score (r=0.50; p=0.05). In conclusion, despite the relatively few patients in our study, these results suggest that OMT significantly improves endothelial function and functional performance in intermittent claudication patients along with benefits in quality of life. This novel treatment combined with drug and lifestyle modification might be an effective alternative to traditional training based on exercise.

Human leucocyte-endothelial interactions in peripheral arterial occlusive disease

Abstract. This ex vivo study determined the expression of leucocyte adhesion receptors for endothelial adhesion molecules in 10 patients with peripheral arterial occlusive disease (PAOD) and in 10 healthy controls before and after treadmill exercise. Granulocytes from venous blood samples were separated on a Ficoll‐Hypaque gradient and the phenotypical expression of CD11a/CD18 (LFA‐1), CD11b/CD18 (Mac‐1) and CD11c/CD18 (p150,95) was observed by double indirect immunofluorescence using specific monoclonal antibodies. The total and differential white blood cell counts were monitored before and after exercise. In the PAOD patients a significant reduction in the number of granulocytes expressing CD11b/CD18 (Mac‐1) and CD11c/CD18 (p150,95) associated with a significant neutropenia was observed after exercise, suggesting that leucocyte‐endothelial interactions occur during ischaemia.