Differences in ionic currents between canine myocardial and Purkinje cells.

An electrophysiological analysis of canine single ventricular myocardial (VM) and Purkinje (P) cells was carried out by means of whole cell voltage clamp method. The following results in VM versus P cells were obtained. INa3 was present, had a threshold negative to the fast activating–inactivating INa1, its slow inactivation was cut off by INa1, and contributed to Na+ influx at INa1 threshold. INa1 was smaller and had a less negative threshold. There was no comparable slowly inactivating INa2, accounting for the shorter action potential. Slope conductance at resting potential was about double and decreased to a minimum value at the larger and less negative IK1 peak. The negative slope region of I-V relation was smaller during fast ramps and larger during slow ramps than in P cells, occurred in the voltage range of IK1 block by Mg2+, was not affected by a lower Vh and TTX and was eliminated by Ba2+, in contrast to P cells. ICa was larger, peaked at positive potentials and was eliminated by Ni2+. Ito was much smaller, began at more positive values, was abolished by less negative Vh and by 4-aminopyridine, included a sustained current that 4-aminopyridine decreased but did not eliminate. Steeper ramps increased IK1 peak as well as the fall in outward current during repolarization, consistent with a time-dependent block and unblock of IK1 by polyamines. During repolarization, the positive slope region was consistently present and was similar in amplitude to IK1 peak, whereas it was small or altogether missing in P cells. The total outward current at positive potentials comprised a larger IK1 component whereas it included a larger Ito and sustained current in P cells. These and other results provide a better understanding of the mechanisms underlying the action potential of VM and P cells under normal and some abnormal (arrhythmias) conditions

Characterization of the slowly inactivating sodium current INa2 in canine cardiac single Purkinje cells

The aim of our experiments was to investigate by means of a whole cell patch-clamp technique the characteristics of the slowly inactivating sodium current (INa2) found in the plateau range in canine cardiac Purkinje single cells. The INa2 was separated from the fast-activating and -inactivating INa (labelledhere INa1)by applying a two-step protocol.Thefirst step, froma holding potential (Vh) of −90 or −80 mV to −50 mV, led to the quick activation and inactivation of INa1. The second step consisted of depolarizations of increasing amplitude from−50 mV to less negative values, which led to the quick activation and slow inactivation of INa2. The INa2 was fittedwith a double exponential functionwith time constants of tens and hundreds milliseconds, respectively. After the activation and inactivation of INa1 at−50 mV, the slope conductance was very small and did not change with time. Instead, during INa2, the slope conductance was larger and decreased as a function of time. Progressively longer conditioning steps at−50 mVresulted in a progressive decrease in amplitude of INa2 during the subsequent test steps. Gradually longer hyperpolarizing steps (increments of 100 ms up to 600 ms) from Vh −30 mV to −100 mV were followed on return to −30 mV by a progressively larger INa2, as were gradually more negative 500 ms steps from Vh −30 mV to−90 mV. At the end of a ramp to−20 mV, a sudden repolarization to approximately−35 mV fully deactivated INa2. The INa2 was markedly reduced by lignocaine (lidocaine) and by low extracellular [Na+], but it was little affected by low and high extracellular [Ca2+]. At negative potentials, the results indicate that there was little overlap between INa2 and the transient outward current, Ito, as well as the calcium current, ICa. In the absence of Ito and ICa (blocked by means of 4-aminopyridine and nickel, respectively), INa2 reversed at 60mV. In conclusion, INa2 is a sodium current that can be initiated after the inactivation of INa1 and has characteristics that are quite distinct from those of INa1. The results have a bearing on the mechanisms underlying the long plateau of Purkinje cell action potential and its modifications in different physiological and pathological conditions

Genetic Polymorphisms of the Natriuretic Peptide System in the Pathogenesis of Cardiovascular Disease: What Lies on the Horizon?

BACKGROUND: The natriuretic peptide hormone family includes various proteins characterized by similar chemical structure and shared biological functions, with important effects on the cardiovascular system. Accordingly, these molecules are widely recognized as key clinical biomarkers in the diagnosis and monitoring of heart failure, hypertension, and coronary heart disease. CONTENT: Several single-nucleotide polymorphisms have been recently identified in genes associated with the natriuretic system. This review provides an overview of new insights into the functional role of these genetic variants, as well as their impact on cardiovascular physiopathology and drug response. CONCLUSIONS: Noteworthy relationships between some specific polymorphisms and clinical correlates of cardiovascular disease have emerged. Nevertheless, future confirming studies are needed to substantiate the clinical relevance of such variants

Costruzione di mondi. Note sul concetto weberiano di Weltbild

This paper aims to focus on the Weberian concept of Weltbild (World-image), considered as one of the most important analytic instruments of his sociology. I will argue that Weltbilder have a mainly cognitive function, with a direct practical effect: they are framing devices, that allow men to orient themselves in the world. In this sense, the Weberian concept of Weltbild differs from the notion of Ideology. I will base my argument on two different elements: the peculiar theoretical status of World-images and their relationship with material factors. Unlike ideologies, in fact, Weltbilder do not deal with the distinction true-false: they are conceivable as cultural constructions, the relationship with whom can only take the form of belief (Glaube). Secondly, they are not simply functional products of material interests: in Weberian analysis, ideal and material factors have a mutual influence, that is not deducible by a rule

Essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino-atrial node discharge

Background: The diastolic oscillatory after-potential Vos and pre-potential ThVos play an essential role in the pacemaker mechanism of sino-atrial node (SAN). The aim of this study was to investigate whether these oscillatory potentials are also involved in adrenergic control of SAN discharge. Methods: Vos and ThVos were visualized by superfusing guinea pig SAN in high [K+]o. The actions of adrenergic agonists on oscillatory potentials were studied by means of a microelectrode technique. Statistical significance was determined by means of Student's paired t-test. Results: In non-spontaneous SAN, norepinephrine (NE) decreased the resting potential into a voltage range ("oscillatory zone") where increasingly larger ThVos appeared and initiated spontaneous discharge. In slowly discharging SAN, NE gradually increased the rate by increasing the amplitude and slope of earlier-occurring ThVos and of Vos until these oscillations fused with initial diastolic depolarization (DD1). In the presence of NE, sudden fast rhythms were initiated by large Vos that entered a more negative oscillatory zone and initiated a large ThVos. Recovery from NE exposure involved the converse changes. The β-adrenergic agonist isoproterenol had similar actions. Increasing calcium load by decreasing high [K+]o, by fast drive or by recovery in Tyrode solution led to growth of Vos and ThVos which abruptly fused when a fast sudden rhythm was induced. Low [Ca2+]o antagonized the adrenergic actions. Cesium (a blocker of If) induced spontaneous discharge in quiescent SAN through ThVos. In spontaneous SAN, Cs+increased Vos and ThVos, thereby increasing the rate. Cs+ did not hinder the positive chronotropic action of NE. Barium increased the rate, as Cs+ did. Conclusion: Adrenergic agonists: (i) initiate SAN discharge by decreasing the resting potential and inducing ThVos; (ii) gradually accelerate SAN rate by predominantly increasing size and slope of earlier and more negative ThVos; (iii) can induce sudden fast rhythms through the abrupt fusion of large Vos with large ThVos; (iv) increase Vos and ThVosby increasing cellular calcium; and (v) do not modify the oscillatory potentials by means of the hyperpolarization-activated current If. The results provide evidence for novel mechanisms by which the SAN dominant pacemaker activity is initiated and enhanced by adrenergic agonists

Oxidative Stress as a predictor of cardiovascular events in coronari artery disease patients

Abstract Background: Enhanced oxidative stress has been associated with atherosclerosis and coronary artery disease (CAD). However, the predictive value of circulating oxidative stress biomarkers for cardiovascular events (CE) in patients with CAD has remained poorly understood. Aim: To assess the prognostic significance of reactive oxygen metabolites, estimated as index of oxidative stress in serum samples by means of a commercial kit (ROMs, Diacron, Italy) on the rate of mortality and major adverse CE (MACE) in CAD. Methods: A study of 93 consecutive patients with angiographically documented CAD (75 males, age: 68?10 years, mean?SD) was made during a mean follow-up of 66 months until the occurrence of one of the following CE: cardiac and all cause death, non-fatal myocardial infarction and coronary revascularization [percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG)]. Patient data were retrospectively collected from the Institute\u27s electronic databank that saves demographic, clinical, instrumental and follow-up data of all patients admitted to our department. Results: The Kaplan-Meier survival estimates showed a significantly worst outcome in patients presenting elevated ROM level (>75th percentile, corresponding to 481 AU) (log rank=11, 7.5, 5.1; p<0.001, p<0.01, p<0.05 for cardiac and all cause death and MACEs, respectively). In a multivariate Cox regression model, elevated oxidative stress remained a significant predictor of cardiac and all cause death [hazard ratio (HR) 3.9, 95% confidence interval, 95% (CI) 1.4-11.1, p=0.01; HR=2.6, 95% CI 1.1-6.2, p=0.02) and MACE (HR=1.8, 95% CI 1.1-3.1, p=0.03)]. Conclusions: The estimation of ROMs may represent an additional prognostic tool in the assessment of CE in CAD patients

Mechanisms of gastroprotection by lansoprazole pre-treatment against experimentally induced injury in rats: role of mucosal oxidative damage and sulfhydryl compounds

This study investigated the mechanisms involved in the protective actions exerted by lansoprazole against experimental gastric injury. Following the intraluminal injection of ethanol-HCl, the histomorphometric analysis of rat gastric sections demonstrated a pattern of mucosal lesions associated with a significant increase in the mucosal contents of malondialdehyde and 8-iso-prostaglandin F(2alpha) (indices of lipid peroxidation), as well as a decrease in the levels of mucosal sulfhydryl compounds, assayed as reduced glutathione (GSH). Pretreatment with lansoprazole 90 micromol/kg, given intraduodenally as single dose or once daily by intragastric route for 8 days, significantly prevented ethanol-HCl-induced gastric damage. The concomitant changes in the mucosal levels of malondialdehyde, 8-iso-prostaglandin F(2alpha) and GSH elicited by ethanol-HCl were also counteracted by lansoprazole. In separate experiments, performed on animals undergoing 2-h pylorus ligation, lansoprazole did not enhance the concentration of prostaglandin E(2), bicyclo-prostaglandin E(2), or nitric oxide (NO) metabolites into gastric juice. Western blot analysis revealed the expression of both type 1 and 2 cyclooxygenase (COX) isoforms in the gastric mucosa of pylorus-ligated rats. These expression patterns were not significantly modified by single-dose or repeated treatment with lansoprazole. Lansoprazole also exhibited direct antioxidant properties by reducing 8-iso-prostaglandin F(2alpha) generation in an in vitro system where human native low-density lipoproteins were subjected to oxidation upon exposure to CuSO(4). The present results suggest that the protective effects of lansoprazole can be ascribed to a reduction of gastric oxidative injury, resulting in an increased bioavailability of mucosal sulfhydryl compounds. It is also proposed that lansoprazole does not exert modulator effects on the gastric expression of COX isoforms as well as on the activity of NO pathways

ESTUDO HIDRÁULICO DOS ORIFÍCIOS DOS FLOCULADORES DE BANDEJAS PERFURADAS SUPERPOSTAS DE ESTAÇÕES DE TRATAMENTO DE ÁGUA

Orifícios afogados, com diâmetros variando entre 6 e 15 mm, foram ensaiados em laboratório com o objetivo de determinar seus coeficientes de descarga ao trabalharem com vazões correspondentes a números de Reynolds não superiores a 11000. Trata-se de diâmetros e condições aplicáveis a floculadores do tipo hidráulico, de bandejas perfuradas, utilizados em estações de tratamento de água pré-fabricadas, destinadas a tratarem pequenas vazões. Os resultados obtidos mostram que o valor 0,61 – normalmente adotado para o coeficiente de descarga de orifícios - não se aplica a essa faixa de diâmetros, quando operando nas condições ensaiadas