Sildenafil Prevents Endothelial Dysfunction Induced by Ischemia and Reperfusion via Opening of Adenosine Triphosphate–Sensitive Potassium Channels

Background— Animal studies have demonstrated that administration of sildenafil can limit myocardial damage induced by prolonged ischemia, an effect that appears to be mediated by opening of adenosine triphosphate–sensitive potassium (K ATP ) channels. No study has investigated whether sildenafil can also prevent the impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) in humans. Methods and Results— In a double-blind, placebo-controlled, crossover design, 10 healthy male volunteers (25 to 45 years old) were randomized to oral sildenafil (50 mg) or placebo. Two hours later, endothelium-dependent, flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). Seven days later, subjects received the other treatment (ie, placebo or sildenafil) and underwent the same protocol. Pre-IR radial artery diameter and FMD, as well as baseline radial artery diameter after IR, were similar between visits ( P =NS). After placebo administration, IR significantly blunted FMD (before IR: 7.9±1.1%; after IR: 1.2±0.7%, P <0.01). Importantly, sildenafil limited this impairment in endothelium-dependent vasodilatation (before IR: 7.0±0.9%; after IR: 6.2±1.1%, P =NS; P <0.01 compared with placebo). In a separate protocol, this protective effect was completely prevented by previous administration of the sulfonylurea glibenclamide (glyburide, 5 mg), a blocker of K ATP channels (n=7; FMD before IR: 10.3±1.5%; after IR: 1.3±1.4%, P <0.05). Conclusions— In humans, oral sildenafil induces potent protection against IR-induced endothelial dysfunction through opening of K ATP channels. Further studies are needed to test the potential clinical implications of this finding

Comparison of blood viscosity using a torsional oscillation viscometer and a rheometer

The absence of a simple and clinically practical method to determine whole blood viscosity can partly justify why the medical community has been slow in realizing the significance of whole blood viscosity. For this reason, the availability of a technique able to evaluate blood viscosity in a rapid and direct manner is welcome. To evaluate the feasibility in hemorheological laboratory of a new torsional oscillation viscometer, it was compared with a conventional cone–plate system. The viscosity comparison has been related to hematocrit value both on whole blood and suspended blood in a saline solution. The results showed a good repeatability and reproducibility of the new equipment, with a best-fitting data of the hematocrit 0–100% range characterized by coefficient of determinations, r2 > 0.95. Furthermore, a comparison of whole blood viscosity as measured by the two instruments was done on blood samples collected from hospitalized patients. Reasonable agreement for the viscosity values was found between the two methods with linear determination coefficients between the two measurement methods comprised between r2 = 0.7329 and 0.9263, depending on shear stress phase and the corresponding shear rate

Evaluation of a Torsional-Vibrating Technique for the Hemorheological Characterization

Clinical measurement of blood viscosity is an important parameter in the diagnosis of different diseases (e.g., diabetes, hypertension, cardiovascular diseases). The significance of blood viscosity in the microcirculatory flow is also of great importance. Thus, a simple and accurate evaluation of hemorheological properties could be an important challenge in clinical practice. Nowadays, validated measurements of plasma viscosity are commonly carried out with rotational viscometers by means of the various geometric configurations. However, red blood cells deform under mechanical force and this aspect could lead to an artificial variation in the apparent viscosity. In this work, an evaluation of a new technique for the viscosity determination is focused. In particular, a torsional oscillation viscometer was adopted (VM10AL, CBC Europe) in the presence and in the absence of stirring conditions at thermostated conditions. The profile of the rheological behaviour as a function of time was recorded and compared with that obtained using a cone-plate rotational viscometer (AR300, TA Instrument)

High levels of human Chromogranin A in umbilical cord plasma and amniotic fluid at parturition.

The human placenta is a neuroendocrine organ that produces several hypothalamic and pituitary hormones that are secreted during pregnancy and parturition into maternal and fetal circulation and amniotic fluid. Human chromogranin A (CgA) is a glycoprotein mainly localized to the adrenal medulla and released in response to several stressful events. During pregnancy, intrauterine tissues express and synthesize CgA mRNA and peptide and secret it into the biologic fluids of pregnancy, so we investigated whether maternal, umbilical, and amniotic human CgA levels are affected by the stress of parturition