Sandro Forconi

New guidelines for hemorheological laboratory techniques

This document, supported by both the International Society for Clinical Hemorheology and the European Society for Clinical Hemorheology and Microcirculation, proposes new guidelines for hemorheolog ...

Evaluation of C-Reactive Protein Measurement for Assessing the Risk and Prognosis in Ischemic Stroke: A Statement for Health Care Professionals From the CRP Pooling Project Members

Background and Purpose— Several studies have shown, in different populations, that modest elevation of plasma C-reactive protein (CRP) in the range seen in apparently healthy individuals is a strong predictor of future vascular events. Elevated plasma CRP concentrations are also associated with an increased risk of cerebrovascular events and an increased risk of fatal and nonfatal cardiovascular events in ischemic stroke patients. These epidemiological and clinical observations suggest that determination of plasma CRP concentrations could be used as an adjunct for risk assessment in primary and secondary prevention of cerebrovascular disease and be of prognostic value. The aim of this review is to summarize the evidence for CRP as an independent predictor of cerebrovascular events in at-risk individuals and ischemic stroke patients and to consider its usefulness in evaluating prognosis after stroke. Summary of Review— CRP fulfils most of the requirements of a new risk and prognostic predictor, but several issues await further confirmation and clarification before this marker can be included in the routine evaluation of stroke patients and subjects at risk for cerebrovascular disease. Potentially important associations have been established between elevated plasma CRP concentrations and increased efficacy of established therapies, particularly lipid-lowering therapy with statins. Conclusion— At present, there is not sufficient evidence to recommend measurement of CRP in the routine evaluation of cerebrovascular disease risk in primary prevention, because there is insufficient evidence as to whether early detection, or intervention based on detection, improves health outcomes, although shared risk of cardiovascular disease indicates this may be of value. In secondary prevention of stroke, elevated CRP adds to existing prognostic markers, but it remains to be established whether specific therapeutic options can be derived from this.

Sildenafil Prevents Endothelial Dysfunction Induced by Ischemia and Reperfusion via Opening of Adenosine Triphosphate–Sensitive Potassium Channels A Human In Vivo Study

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 (KATP) 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 KATP 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 KATP channels. Further studies are needed to test the potential clinical implications of this finding.

Prognostic role of C-reactive protein in very old patients with acute ischaemic stroke

Background and scope.  Recent literature has demonstrated that inflammation contributes to all phases of atherosclerosis and brain damage caused by stroke. In acute phase of cerebrovascular diseases biochemical markers of inflammation, such as C‐reactive protein (CRP), could represent an indicator of severity of stroke, but few studies have verified this hypothesis, especially in very old patients. The aim of this study was to evaluate the role of CRP on short‐ and long‐term prognosis in 75‐year old and over elderly patients with acute ischaemic stroke.

Endothelium and hemorheology

Hemorheological alterations which can be found in ischaemic vascular diseases are well known and widely studied; less clear is the relationship between these alterations and endothelial function. Our studies showed that modifications in endothelial function caused by physical stress are associated with a worsening in hemorheological parameters mainly in patients affected by ischaemic vascular diseases: major vascular alterations have been found in patients with very high levels of plasma markers endothelial dysfunction. The control of the basal tone of the vessels is given by the complex interaction between vasoconstrictor and vasodilator endothelial factors and when this equilibrium is broken we have the endothelial dysfunction. From a methodological point of view we can find an endothelial dysfunction index determining the various substances produced by the endothelium, but it is very difficult to have a value which clearly identifies the real state of the endothelial alteration. The function of the NO, which is one of the more powerful endogenous vasodilators and whose synthesis is catalysed by nitric oxide synthase (NOS), can be determined by the ratio between blood concentrations of citrulline and arginine (the co-product and the precursor of the way of NO synthesis), which represents the level of activity of the enzyme. A very affordable index of the endothelial dysfunction is the asymmetric dimethylarginine (ADMA), a powerful endogenous inhibitor of NOS; in fact several studies demonstrated a strong relationship between ischaemic vascular diseases and high levels of plasma ADMA. Evaluation of these parameters is measured by means of high performance liquid chromatography (HPLC): this technique provides very affordable results and allows to obtain evaluations of substances in very small concentrations, like ADMA.

The evolution of the meaning of blood hyperviscosity in cardiovascular physiopathology: should we reinterpret Poiseuille?

In the 1960s and 1970s, a number of researchers (including ourselves) involved in the study of cardiovascular pathophysiology and particularly in the development of techniques to quantify blood flow, came across the observation that, along with vessel diameter, also blood viscosity plays an important role not only in theory but also in practice. Until then, viscosity was thought to play only a marginal role in determining blood flow, a concept which was based on the 1828 theories of Jean Louis Marie Poiseuille (Fig. 1, and [1]).1 In his well-known formula, named after its fathers Hagen2 and Poiseuille,

Plasma D-Dimer Levels in Elderly Patients with Suspected Pulmonary Embolism

been shown to be a useful aid in the diagnosis of PE. DD, a degradation product of cross-linked fibrin, has high sensitivity (89‐98.8%) and high

Pulmonary embolism in the elderly: clinical, instrumental and laboratory aspects.

Objective: To focus on diagnostic and therapeutic problems of pulmonary embolism in the elderly. Methods: Retrospective analysis of 5 years of clinical, instrumental, and laboratory data (collected at the time of hospital admission) for patients 65 years and older with pulmonary embolism proven by a high-probability scintigraphic lung scan or necropsy. Sixty-eight patients, 46 females and 22 males, 78.61 ± (SD) 7.71 years old, were enrolled in the study. Results: Dyspnea, chest pain, tachycardia, and tachypnea were the most common symptoms and signs; they were present alone or in combination in all patients. Bed rest over 4 days was found in 65% of the patients and deep vein thrombosis in the leg in 35%. Only 7 patients were on anticoagulant therapy which was likely to reduce the incidence of pulmonary embolism. The mortality was 29.5%. Major bleeding due to anticoagulant therapy was observed in 4.4% of the patients; 1 case was fatal. Sinus tachycardia, ST segment and T wave abnormalities in anterior leads, and incomplete bundle branch block were the most frequent electrocardiographic findings. Chest X-ray was normal in 19.5% of the patients and compatible with pulmonary embolism in 10%. A transthoracic two-dimensional echocardiogram was abnormal in 74% of the cases, with involvement of the right ventricle in the majority of them. Many patients had laboratory parameters within the normal range. The value of the latex agglutination D-dimer assay was less than the cutoff value of 500 µg/l in 16% of the patients. Hypoxemia and a high alveolar-arterial oxygen gradient were the most frequent aspects of the arterial blood gas analysis. Respiratory alkalosis was observed in only one third of the patients. Conclusions: Pulmonary embolism is often underdiagnosed in the elderly. Clinical, instrumental, and laboratory findings are nonspecific. Only acute suspicion can increase the number of diagnoses, reduce the time to diagnosis, and improve the prognosis.

Strain Gauge Plethysmography in the Study of Circulation of the Limbs

Plethysmography means registration of spontaneous or provoked volume changes in a segment of the body, with which it is possible to obtain information on the circulation of blood in that segment. This method has been known for a long time and has been applied by physiologists to several circulatory problems. However, the first plethysmographic instruments, water plethysmographs, presented such difficult technical problems that their use was restricted to sophisticated research in animals and only rarely in man. The water-filled plethysmograph was then replaced by the air-filled types, but these instruments also had grave technical problems. The principle of the so-called impedance plethysmography or rheography is based on electric impedance changes when a high-frequency and low-power alternating electric current passes through the body segment under investigation. This method, developed in the 1950s and designed to detect pulse waves in the limb, does not really reflect volume changes, but changes in the electrolyte content of the segment; so it cannot be compared with methods developed to measure blood flow.

Nitroglycerine causes mitochondrial reactive oxygen species production: In vitro mechanistic insights

BACKGROUND Nitroglycerine (GTN) is an organic nitrate that has been used for more than 100 years. Despite its widespread clinical use, several aspects of the pharmacology of GTN remain elusive. In a recent study, the authors of the present study showed that GTN causes opening of the mitochondrial permeability transition pore (mPTP) and mitochondrial production of reactive oxygen species (ROS). OBJECTIVE In the present study, it was tested whether GTN-induced ROS production depends on mitochondrial potassium ATP-dependent channel or mPTP opening, and/or GTN biotransformation. METHODS AND RESULTS Isolated rat heart mitochondria were incubated with succinate (a substrate for complex II) and GTN, causing immediate ROS production, as manifested by chemiluminescence. This ROS production was prevented by concomitant vitamin C incubation. Conversely, inhibitors of potassium ATP-dependent channels, mPTP opening or of GTN biotransformation did not modify ROS production. CONCLUSIONS GTN triggers mitochondrial ROS production independently of the opening of mitochondrial channels and/or of GTN biotransformation. The present data, coupled with previous evidence published by the same authors that GTN causes opening of mPTPs, provide further evidence on the pharmacology of GTN. It is proposed that GTN causes direct uncoupling of the respiratory chain, which determines ROS production and subsequent mPTP opening. The clinical implications of these findings are also discussed.