Erythrocyte Membrane Fluidity Alterations in Sudden Sensorineural Hearing Loss Patients: The Role of Oxidative Stress.

Introduction Sudden sensorineural hearing loss (SSNHL) involves an acute unexplained hearing loss, nearly always unilateral, that occurs over less than a 72-hour period. SSNHL pathogenesis is not yet fully understood. Cochlear vascular occlusion has been proposed as a potential mechanism of hearing damage and cochlear ischaemia has been related to alterations of cochlear microvessels. In addition, some researchers have focused their attention on the rheological alterations and blood hyperviscosity. Erythrocyte deformability plays a key role in determining blood viscosity, and it is critical to cochlear perfusion. It has been shown that oxidative stress-induced erythrocyte membrane fluidity alterations are linked to the progression of cardiovascular diseases. Methods To determine whether erythrocytes from SSNHL patients show signs of oxidative stress, and whether this condition can modify the haemorheologic profile in these patients, we analysed haemorheologic profile and erythrocyte oxidative stress in 35 SSNHL patients and 35 healthy subjects, matched for age and sex. Fluorescence anisotropy was used to evaluate the fluidity of erythrocyte membranes. Results Our results show a significant structural and functional involvement of erythrocyte membrane alterations in SSNHL, as well as elevated levels of membrane lipid peroxidation and intracellular reactive oxygen species (ROS) production. In addition, erythrocyte-derived ROS and erythrocyte lipid peroxidation positively correlated with whole blood viscosity and erythrocyte deformability. Moreover, in vitro experiments demonstrated that ROS display a key role in erythrocyte membrane fluidity. Conclusion These findings indicate that erythrocyte oxidative stress plays a key role in the pathogenesis of SSNHL and pave the way to new therapeutic interventions.

TAFI activity and antigen plasma levels are not increased in acute coronary artery disease patients admitted to a coronary care unit.

INTRODUCTION: Hypofibrinolysis, at least in part due to high levels of plasminogen activator inhibitor-1 (PAI-1), has been reported to occur frequently in patients with coronary artery disease (CAD). A recently described carboxypeptidase, thrombin-activatable fibrinolysis inhibitor (TAFI), is involved in the regulation of the balance between coagulation and fibrinolysis. High TAFI plasma levels may therefore contribute to a hypofibrinolytic state and to an increased risk for thrombotic disorders. There are contradictory results regarding TAFI levels in CAD patients, possibly because the characteristics of patients investigated and the time of blood sampling were different among different studies. MATERIALS AND METHODS: Fibrinolytic inhibitors (TAFI activity, TAFI antigen and PAI-1 activity plasma levels) were measured in 44 consecutive patients admitted to the Coronary Care Unit of the University of Florence and in a group of 44 healthy controls, matched for age and sex, to detect a possible association of their levels with acute CAD. RESULTS: No differences were found in TAFI levels, either activity or antigen, between patients and controls. PAI-1 activity was significant different between patients and controls (p=0.0001). The frequencies of TAFI activity and antigen over cut-off levels were similar in patients and controls. Instead, higher PAI-1 levels were more frequent (p=0.04) in patients respect to controls. The univariate analysis confirmed the association of increased PAI-1 levels with acute CAD [OR=3.3; p=0.04]. Among the patients, TAFI and PAI-1 levels were not different according to clinical presentation of symptoms or indication to immediate percutaneous revascularization. CONCLUSION: Our study suggests that in acute phase of CAD no increased levels of TAFI are detectable in plasma.

Reduced erythrocyte deformability and hypercoagulability in idiopathic sudden sensorineural hearing loss.

OBJECTIVE: Sudden sensorineural hearing loss is a frequent disease whose aetiology is still unknown in about 80% of patients. Aim of this study was to evaluate if haemorheological changes and some indexes of hypercoagulability and hypofibrinolysis are associated with idiopathic sudden sensorineural hearing loss (ISSHL). METHODS: We studied 63 patients with ISSHL and 67 healthy control subjects, matched for age, sex and traditional cardiovascular risk factors. Haemorheological studies were performed by assessing whole blood viscosity (WBV) at 0.512 s(-1) and 94.5 s(-1), plasma viscosity (PLV) and erythrocyte deformability index (DI). To assess whole blood coagulation Sonoclot analysis was performed. Sonoclot variables studied were Sonoclot activated clotting time (SonACT), clot rate and time to peak. Fibrinogen, PAI-1 antigen (ag) and factor VIII:C plasma levels were also measured. RESULTS: WBV, PLV, SonACT, clot rate, time to peak, PAI-1ag and factor VIII:C were significantly altered in patients in comparison with controls (p<0.05). A multivariate analysis (adjusted for traditional cardiovascular risk factors, hematocrit, fibrinogen, haemostatic and haemorheological variables) indicated that WBV at 94.5 s(-1), DI, SonACT, clot rate, PAI-1ag plasma levels and factor VIII:C activity were independently associated with ISSHL (p<0.05). CONCLUSIONS: The observed changes in viscosity, blood clotting and fibrinolysis may contribute, at least in part, to the pathophysiological mechanism of ISSHL.

Is tissue factor pathway inhibitor a marker of procoagulable status in healthy infertile women undergoing ovarian stimulation for assisted reproduction?

Increased serum estradiol levels occurred during ovarian stimulation for assisted reproduction. Tissue factor pathway inhibitor (TFPI) plays a relevant role in regulating haemostatic equilibrium, and its decrease has been documented in conditions in which blood coagulation occurs. We investigated TFPI concentrations and coagulative pathway in healthy infertile women undergoing ovarian stimulation. We investigated 27 healthy infertile women, median age 37 (25-41) years, undergoing ovarian stimulation, observed during the mid-luteal phase of cycle (T0) and on day 5 (T1), and between day 7 and 9 (T2) of ovarian stimulation. Coagulative pathway was assessed by a global test [endogenous thrombin potential, (ETP)] and TFPI concentrations. TFPI values progressively and significantly decreased throughout the ovarian stimulation procedure (P = 0.03), contemporarily estradiol levels progressively and significantly increased from baseline to T2 (P < 0.0001). A significant negative correlation between changes in estradiol and TFPI levels was observed (P = 0.03). As concerns ETP parameters a significant increase of ETP (mA) and Cmax (mA/min) throughout the ovarian stimulation cycle was found (P = 0.003 and P = 0.002, respectively). TFPI values progressively and significantly decreased throughout the ovarian stimulation, and negatively correlated with estradiol, thus suggesting that TFPI may represent one of the main 'actors' involved in the hypercoagulable status, occurring during assisted reproduction. The relationship between TFPI and estradiol levels might contribute to the knowledge of mechanisms able to modify a quite milieu into a prothrombotic status. Nevertheless, the small number of individuals investigated might influence the relevance of our results.

Hemorheologic profile in healthy women undergoing controlled ovarian stimulation.

We investigated the hemorheologic profile in 110 women undergoing controlled ovarian stimulation and provide evidence that smokers and women with body mass index>25 kg/m2 exhibit alterations of rheologic profile. A progressive increase of whole-blood viscosity throughout the ovarian stimulation cycle was observed; deformability and aggregation of erythrocytes decreased from baseline to the beginning of recombinant FSH administration, then remained unchanged throughout the next days; hematocrit mildly decreased during the last days of recombinant FSH administration; and fibrinogen and cholesterol levels decreased and increased, respectively, throughout the stimulation cycle.