Clinical and hemodynamic performance of the Freestyle aortic root bioprosthesis.

Background: The objective of this study is to assess the clinical and hemodynamic performance of a stentless porcine bioprosthesis, the Freestyle aortic root bioprosthesis.

Methods: Consenting patients requiring isolated aortic valve or aortic root replacement received the Freestyle bioprosthesis. Clinical follow-up and echocardiographic data were obtained at discharge, 3 to 6 months, 1 year, and annually thereafter.

Biliopancreatic diversion (doudenal switch procedure).

The physiological principle underlying biliopancreatic diversion (BPD) is attractive. It decreases food absorption and particularly that of fat. It preserves normal eating habits and is compatible with a good quality of life.

Usefulness of the indexed effective orifice area at rest in predicting an increase in gradient during maximum exercise in patients with a bioprosthesis in the aortic valve position.

This study examines the hemodynamic behavior of aortic bioprosthetic valves during maximum exercise. Nineteen patients with a normally functioning stented bioprosthetic valve and preserved left ventricular function were submitted to maximum ramp bicycle exercise. In 14 of the 19 patients, valve effective orifice area and mean gradient were measured at rest and during exercise using Doppler echocardiography.

Reduction of caveolin 1 gene expression in lung carcinoma cell lines.

Caveolae are plasma membrane microdomains that have been implicated in organizing and concentrating certain signaling molecules. Caveolins, constitute the main structural proteins of caveolae. Caveolae are abundant in terminally differentiated cell types.

Thioridazine lengthens repolarization of cardiac ventricular myocytes by blocking the delayed rectifier potassium current.

Proarrhythmia has been observed with the antipsychotic agent thioridazine (THIO). The mechanisms underlying these effects are unknown. The objectives of this study were 1) to characterize the effects of THIO on cardiac repolarization and 2) to determine whether lengthening of the Q-T interval could be explained by blocking major K+-repolarizing currents.

Hemodynamic features of the freestyle aortic bioprosthesis compared with stented bioprosthesis.

Background: The Freestyle prosthesis is a new stentless aortic bioprosthesis. Anticipated benefits are improved hemodynamics and increased longevity.

Methods: Doppler echocardiograms were performed early and at 3 to 6 months, 1 year, and 2 years after operation in 157 patients (69 men, 88 women, aged 48 to 85 years) with this prosthesis, and results were compared with hemodynamic data in patients with Intact and Mosaic stented bioprostheses.

Rapidly evolving constrictive tuberculous pericarditis: case presentation and review of the literature.

A 69-year-old male presented with a diagnosis of idiopathic pericarditis, first treated with prednisone for a few weeks with resolution of the symptoms. A few days after stopping the medication, he presented with malaise, cough and signs of pericardial constriction confirmed by echocardiography. He was diagnosed with pulmonary tuberculosis with pericardial involvement and treated accordingly.

Block of potassium currents in guinea pig ventricular myocytes and lengthening of cardiac repolarization in man by the histamine H1 receptor antagonist diphenhydramine.

Treatment with second generation histamine H1 receptor antagonists has been associated with lengthening of the Q-T interval and proarrhythmia. Similarly, lengthening of the Q-T interval has been reported in patients after overdosing with diphenhydramine (DPH), a first generation agent. Therefore, our study was designed 1) to assess effects of DPH on cardiac repolarization and 2) to characterize effects of the drug on major voltage-dependent cardiac K+ currents.

The many aspects of endothelins in ischemia-reperfusion injury: emergence of a key mediator.

The endothelins (ETs) are regulatory peptides, distributed in many organ systems and producing potent physiological effects. They are the most powerful vasoconstrictive substances known today. They also act as promitogens.

Attenuation of myocardial ischemia with repeated exercise in subjects with chronic stable angina: relation to myocardial contractility, intensity of exercise and the adenosine triphosphate-sensitive potassium channel.

Objectives: This study characterized the attenuation of myocardial ischemia observed with re-exercise to determine whether: 1) a differing exercise intensity modifies this attenuation; 2) it could be explained by contractile down-regulation or stunning; 3) it is mediated by activation of ATP-sensitive potassium channels (K+-ATP).

Background: Subjects with ischemic heart disease (IHD) frequently note less angina with re-exercise after a brief rest. Potential mechanisms of this 'warm-up' phenomenon have been little explored.

Atherogenic, hemostatic, and other potential risk markers in subjects with previous isolated myocardial infarction compared with long-standing uncomplicated stable angina.

Background: Several atherogenic, hemostatic, inflammatory, and genetic parameters and markers have been implicated as risk factors in coronary artery disease, although whether they are risk factors for acute as opposed to chronic coronary disease is unclear.

Methods And Results: Fifty subjects with an isolated myocardial infarction >3 months previously were compared with 50 subjects with a minimum 3-year history of stable angina, documented coronary artery disease, normal electrocardiogram and normal ventricular wall motion, and no episode suggesting infarction or unstable angina. Biologic variables analyzed included apolipoprotein B (apo B), lipoprotein (a), C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (TPA) and inhibitor (PAI-1), thrombin-antithrombin (TAT), fragment 1+2 (F1+2), von Willebrand factor (vWF), activated protein C resistance, homocyst(e)ine, anticardiolipin antibodies, blood group, and the angiotensin-converting enzyme insertion/deletion (I/D) and angiotensin II receptor gene polymorphisms.

Biliopancreatic diversion with duodenal switch.

In 1990 Scopinaro's technique of biliopancreatic diversion with distal gastrectomy (DG) and gastroileostomy was modified. A sleeve gastrectomy with duodenal switch (DS) was used instead of the distal gastrectomy; and the length of the common channel was made 100 cm instead of 50 cm. A questionnaire and a prescription for blood work were sent to 252 patients who underwent DG a mean 8.

Extrapore residues of the S5-S6 loop of domain 2 of the voltage-gated skeletal muscle sodium channel (rSkM1) contribute to the mu-conotoxin GIIIA binding site.

The tetradomain voltage-gated sodium channels from rat skeletal muscle (rSkM1) and from human heart (hH1) possess different sensitivities to the 22-amino-acid peptide toxin, mu-conotoxin GIIIA (mu-CTX). rSkM1 is sensitive (IC50 = 51.4 nM) whereas hH1 is relatively resistant (IC50 = 5700 nM) to the action of the toxin, a difference in sensitivity of >100-fold.

Electrophysiological study of chimeric sodium channels from heart and skeletal muscle.

The alpha-subunit cDNAs encoding voltage-sensitive sodium channels of human heart (hH1) and rat skeletal muscle (rSkM1) have been expressed in the tsA201 mammalian cell line, in which inactivation properties appear to be normal in contrast to Xenopus oocytes. A series of rSkM1/hH1 chimeric sodium channels has been evaluated to identify the domains of the alpha-subunits that are responsible for a set of electrophysiological differences between hH1 and rSkM1, namely, midpoints and slope factors of steady-state activation and inactivation, inactivation kinetics and recovery from inactivation kinetics and their voltage-dependence. The phenotype of chimeric channels in which each hH1 domain was successively introduced into a rSkM1 alpha-subunit framework confirmed the following conclusions.

In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists.

Classic antihistamines, namely diphenhydramine, chlorpheniramine, clemastine, perphenazine, hydroxyzine, and tripelennamine, share structural features with substrates and inhibitors of the polymorphic cytochrome P450 (CYP) isozyme CYP2D6. Therefore, the current study was undertaken to characterize the in vitro inhibition of CYP2D6 by these commonly used, histamine H1 receptor antagonists. Microsomal incubations were performed using bufuralol as a specific CYP2D6 substrate and microsomes derived from human cells transfected with CYP2D6 cDNA.

Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors.

The recent development of specific competitive inhibitors of the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase such as lovastatin, simvastatin, pravastatin and fluvastatin has provided an important new and effective approach to the treatment of hyperlipidaemia and atherosclerosis. These agents are designed to be hepatoselective because the primary site of cholesterol synthesis is the liver and peripheral inhibition of cholesterol synthesis would be more likely to cause adverse drug effects. In this review, Bettina Hamelin and Jacques Turgeon discuss how specific physico-chemical and pharmacological properties (first-pass effect or carrier-mediated uptake) confer hepatoselectivity to either lipophilic or hydrophilic HMG-CoA reductase inhibitors.

Block of the rapid component of the delayed rectifier potassium current by the prokinetic agent cisapride underlies drug-related lengthening of the QT interval.

Background: Lengthening of the QT interval and torsades de pointes resulting in cardiac arrests and deaths have been noticed during treatment with cisapride, a newly developed gastrointestinal prokinetic agent. The rapid (I[Kr]) and slow (I[Ks]) components of the delayed rectifier current (I[K]) are candidate ionic currents to explain cisapride-related toxicity because of their role in repolarization of cardiac ventricular myocytes. Our objectives were to (1) characterize effects of cisapride on two major time-dependent outward potassium currents involved in the repolarization of cardiac ventricular myocytes, I(Kr) and I(Ks), and (2) determine action potential-prolonging effects of cisapride on isolated hearts.

Improved high-performance liquid chromatographic assay for the determination of procainamide and its N-acetylated metabolite in plasma: application to a single-dose pharmacokinetic study.

An improved high-performance liquid chromatographic assay for the determination of procainamide and N-acetylprocainamide (NAPA) at concentrations observed up to 32 h after a single oral dose administration of procainamide to human subjects is reported. Following liquid-liquid extraction of plasma samples, procainamide, NAPA, and the internal standard (N-propionylprocainamide) are separated on a reversed-phase C8 column with retention times of 4.0, 6.

Role of CYP2D6 in the N-hydroxylation of procainamide.

Sequential oxidations at the arylamine moiety of the procainamide molecule leading to the formation of N-hydroxyprocainamide and its nitroso derivative may be responsible for lupus erythematosus observed in patients treated with the drug. The objective of the present study was to characterize major cytochrome P450 isozyme(s) involved in the N-hydroxylation of procainamide. Firstly, incubations were performed with microsomes from either lymphoblastoid cells or yeast transfected with cDNA encoding for specific human cytochrome P450 isozymes.

Block of IKs by the diuretic agent indapamide modulates cardiac electrophysiological effects of the class III antiarrhythmic drug dl-sotalol.

Indapamide is a diuretic agent with direct electrophysiological effects on ionic currents involved in cardiac repolarization. In particular, indapamide blocks the slow component of delayed rectifier potassium current. In contrast, most class III antiarrhythmic agents, such as dl-sotalol, block the rapid component of delayed rectifier potassium current.

A reappraisal of exercise electrocardiographic indexes of the severity of ischemic heart disease: angiographic and scintigraphic correlates.

Objectives: We explored how the exercise electrocardiographic (ECG) indexes generally presumed to signify severe ischemic heart disease (IHD) correlate with coronary angiographic and scintigraphic myocardial perfusion findings.

Background: In exercise testing, it is generally assumed that the early onset of ST segment depression and its occurrence at a low rate-pressure product (ischemic threshold); the amount of maximal ST segment depression; and a horizontal or downsloping ST segment and its prolonged recovery after exercise signify more severe IHD. However, the relation of these indexes to coronary angiographic and exercise myocardial perfusion findings in patients with IHD is unclear.

Effects of cadmium and nisoldipine on the delayed rectifier potassium current in guinea pig ventricular myocytes.

Block of the slow inward calcium current (Isi) during assessment of the delayed rectifier potassium current (IK) of cardiac ventricular myocytes is commonly achieved by use of either inorganic compounds such as cadmium or dihydropyridine derivatives such as nisoldipine. Effects of these two Isi blockers on IK characteristics of guinea pig ventricular myocytes were compared in this study. Currents were measured in the whole cell configuration of the patch-clamp technique and IK tail amplitudes were measured at -40 mV after depolarizations to various test potentials (voltage steps, -20 to +50 mV) for either 250 (IK250), 450 (IK450) or 5000 (IK5000) msec.

Restoration of fast inactivation in an inactivation-defective human heart sodium channel by the cysteine modifying reagent benzyl-MTS: analysis of IFM-ICM mutation.

It has been suggested that the region linking domain III and IV of voltage-gated sodium channels forms the inactivation gate. A combination of site-directed mutagenesis, cysteine covalent modification, and electrophysiological recording techniques was used to identify the role of the Phe1486, a conserved phenylalanine residue located in the III-IV linker of Na+ channels. This Phe1486 is part of a hydrophobic amino acid cluster (IFM) that was proposed to play an essential role in the fast inactivation of voltage-gated sodium channels.

Increase in the proliferative capacity of human myoblasts by using the T antigen under the vimentin promoter control.

Normal myoblasts have a strictly limited growth potential and senesce after a defined number of population doubling. The objective of this study was to determine whether the proliferative capacity of human myoblasts could be extended without inhibiting myogenic differentiation. We have established a stable transfected human myoblast cell line that expresses the SV 40 large T antigen under the control of the human vimentin promoter.