Prior meal enhances the plasma glucose lowering effect of exercise in type 2 diabetes.

Purpose: To compare the changes in plasma glucose and insulin levels in response to 1 h of exercise performed at 60% of VO(2peak) either in the fasted state or 2 h after a standardized breakfast in subjects with type 2 diabetes.

Methods: Ten sedentary men with type 2 diabetes treated with oral agents and not under strict metabolic control were tested on two occasions (fasted and fed state) in a random order at a 1-wk interval.

Results: Plasma glucose was slightly but not significantly higher at the beginning of exercise performed in the fed state versus the fasted state (12.

Biological profiles in subjects with recurrent acute coronary events compared with subjects with long-standing stable angina.

Background: At one end of the clinical spectrum of coronary artery disease (CAD) are subjects who have had repeated acute ischemic events, and at the other end are those with long-standing angina who have never been unstable. This study tests the hypothesis that a specific biological profile can distinguish these 2 extreme groups and predict acute coronary events.

Methods And Results: Blood levels of lipoprotein(a), homocysteine, tissue plasminogen activator, plasminogen activator inhibitor-1, C-reactive protein (CRP), fibrinogen, and von Willebrand factor were compared in 3 groups of 50 subjects each: (1) those with previous multiple acute coronary events, (2) age-matched subjects with >/=3 years of stable angina and no prior acute coronary events, and (3) matched controls without evidence of atherosclerotic disease and a normal coronary angiogram.

Comparison of valve resistance with effective orifice area regarding flow dependence.

Aortic valve resistance has been proposed to represent the severity of aortic stenosis because some studies observed that it was less affected by change in flow than the valve-effective orifice area, but this issue remains controversial. The objective of this study was to systematically analyze the theoretical and practical determinants of these parameters in relation to changes in flow. Valve area and resistance in different valves were studied in vitro in a pulse duplicator system at different flow rates and in vivo in 90 subjects referred to either exercise or dobutamine infusion.

Novel mechanism for Brugada syndrome: defective surface localization of an SCN5A mutant (R1432G).

The SCN5A gene encodes the alpha subunit of the human heart sodium channel (hH1), which plays a critical role in cardiac excitability. Mutations of SCN5A underlie Brugada syndrome, an inherited disorder that leads to ventricular fibrillation and sudden death. This study describes changes in cellular localization and functional expression of hH1 in a naturally occurring SCN5A mutation (R1432G) reported for Brugada syndrome.

Preconditioning in the absence or presence of sustained ischemia modulates myocardial Cx43 protein levels and gap junction distribution.

In the heart, brief repeated episodes of ischemia prior to a sustained occlusion (ischemic preconditioning; PC) significantly delay the onset of necrosis and arrhythmogenesis. Ischemia has been reported to influence gap junction organization and connexin43 (Cx43) content, but whether PC affects these structures is not known. We investigated the effect of PC (2 cycles of 5-min ischemia plus 10-min reperfusion) followed by prolonged reperfusion without concomitant regional coronary occlusion on the myocardial Cx43 content and its spatial distribution in rabbit hearts.

Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity.

Recent studies have suggested that elevated plasma C-reactive protein (CRP) levels are associated with the features of insulin resistance syndrome. In the present study, we have examined the contribution of body composition measured by hydrostatic weighing and of abdominal adipose tissue (AT) accumulation assessed by computed tomography to the variation in plasma CRP levels associated with atherogenic dyslipidemia of the insulin resistance syndrome in a sample of 159 men, aged 22 to 63 years, covering a wide range of adiposity (body mass index values from 21 to 41 kg/m(2)). Plasma CRP levels showed positive and significant correlations with body fat mass (r=0.

Patient-prosthesis mismatch can be predicted at the time of operation.

Background: Patient-prosthesis mismatch is a frequent cause of high postoperative gradients in normally functioning prostheses. The objective of this study was to determine whether mismatch can be predicted at the time of operation.

Methods: Indices used to predict mismatch were valve size, indexed internal geometric area, and projected indexed effective orifice area (EOA) calculated at the time of operation, and results were compared with indexed EOA and mean gradients measured by Doppler echocardiography after operation in 396 patients.

Randomized trial of a noninvasive strategy to reduce hospital stay for patients with low-risk myocardial infarction.

Objectives: This study evaluated the feasibility, pertinence and psychosocial repercussions of a noninvasive reduced hospital stay strategy (three days) for low-risk patients with acute myocardial infarction using simple clinical criteria and predischarge 24-h ambulatory ST-segment ischemic monitoring.

Background: Previous studies evaluating shorter stays for uncomplicated myocardial infarction have been limited by retrospective or nonrandomized design and overdependence on invasive cardiac procedures.

Methods: One-hundred twenty consecutive patients admitted with an acute myocardial infarction fulfilling low-risk criteria were randomized 2:1 to a short hospital stay (80 patients) or standard stay (40 patients).

Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans.

CYP2D6 is the major enzyme involved in the metabolism of venlafaxine. Subjects with a low CYP2D6 activity have increased plasma concentrations of venlafaxine that may predispose them to cardiovascular side effects. In vitro and in vivo studies showed that diphenhydramine, a nonprescription antihistamine, can inhibit CYP2D6 activity.

Hydrogen peroxide modifies the kinetics of HERG channel expressed in a mammalian cell line.

Reactive oxygen species such as H2O2 were shown to influence both electrical and contractile properties of the heart. H2O2 modulates action potential duration and leads to reperfusion-induced arrhythmias. As these effects could involve the modulation of repolarizing currents, we assessed effects of H2O2 on HERG (which encodes the cardiac potassium channel I(Kr)) expressed in Chinese hamster ovary cells.

Myocardial perfusion imaging findings and the role of adenosine in the warm-up angina phenomenon.

Objectives: This study examined the roles of myocardial perfusion and adenosine in warm-up angina.

Background: In warm-up angina, neither the role of an adenosine-mediated mechanism, as is found in experimental ischemic preconditioning, nor of increased myocardial perfusion is well defined.

Methods: In substudy A, a single-photon emission computed tomography (SPECT)-thallium-201 exercise test was performed by 12 subjects with ischemic heart disease on three occasions one week apart.

Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy.

Objective: Because a pseudonormal pattern of ventricular filling has never been considered in studies that reported a prevalence of left ventricular diastolic dysfunction (LVDD) between 20 and 40%, our aim was to more completely evaluate the prevalence of LVDD in subjects with diabetes.

Research Design And Methods: We studied 46 men with type 2 diabetes who were aged 38-67 years; without evidence of diabetic complications, hypertension, coronary artery disease, congestive heart failure, or thyroid or overt renal disease; and with a maximal treadmill exercise test showing no ischemia. LVDD was evaluated by Doppler echocardiography, which included the use of the Valsalva maneuver and pulmonary venous recordings to unmask a pseudonormal pattern of left ventricular filling.

HDL-cholesterol as a marker of coronary heart disease risk: the Québec cardiovascular study.

Background: Primary as well as secondary prevention trials have shown the relevance of lowering LDL-cholesterol to reduce coronary heart disease (CHD) risk. However, although the association between LDL-cholesterol and CHD is well recognized, there is a considerable overlap in the distribution of plasma LDL-cholesterol levels between CHD patients and healthy subjects. The objective of the present review article is to use data from the Quebec cardiovascular study to demonstrate that in men, a low HDL-cholesterol may be even more of a risk factor and a target for therapy than a high LDL-cholesterol.

Effect of angiotensin inhibition on the coronary artery lower pressure limit in anesthetized dogs.

The renin-angiotensin system plays a critical role in regulating vasoconstriction and vasodilatation that can influence myocardial blood flow and its transmural distribution. We tested the hypothesis that angiotensin inhibition can induce a leftward shift of the coronary autoregulatory pressure-flow relation and preserve distribution of myocardial blood flow at lower coronary perfusion pressures. We established circumflex artery pressure-flow relations under baseline conditions and after intracoronary enalaprilat or losartan potassium.

Midterm echocardiographic follow-up after Ross operation.

Background: The pulmonary autograft (Ross) operation is an attractive treatment for aortic valve disease, but hemodynamic follow-up is not well defined.

Methods And Results: One hundred thirty-two consecutive patients (62% male, mean age 40+/-11 years) were followed up to 5 years after the Ross operation. Echocardiography was performed early (within 30 days), 3 to 6 months, and yearly after surgery.

Hemodynamic performance during maximum exercise in adult patients with the ross operation and comparison with normal controls and patients with aortic bioprostheses.

This study examines the resting and exercise hemodynamic performance of the pulmonary autografts in the aortic position as well as of the homografts used for right ventricular outflow reconstruction in patients undergoing the Ross operation. Previous studies have reported excellent resting hemodynamics in patients who underwent aortic valve replacement with a pulmonary autograft. However, there are very few studies of their hemodynamic performance during exercise.

Hemodynamic and clinical impact of prosthesis-patient mismatch in the aortic valve position and its prevention.

Prosthesis-patient mismatch is present when the effective orifice area of the inserted prosthetic valve is less than that of a normal human valve. This is a frequent problem in patients undergoing aortic valve replacement, and its main hemodynamic consequence is the generation of high transvalvular gradients through normally functioning prosthetic valves. The purposes of this report are to present an update on the concept of aortic prosthesis-patient mismatch and to review the present knowledge with regard to its impact on hemodynamic status, functional capacity, morbidity and mortality.

Impact of time interval from the last meal on glucose response to exercise in subjects with type 2 diabetes.

We evaluate the influence of the time interval from the last meal on the blood glucose response to exercise in men with type 2 diabetes. Nineteen men with type 2 diabetes participated in an exercise training program carried out at 60% of maximal oxygen uptake (VO2peak) for 1 h, 3 times a week. Capillary whole blood glucose was measured immediately before and after each exercise session, and the time interval from the last meal (breakfast, lunch, or dinner) was recorded.

Pharmacokinetic and pharmacodynamic interaction between mexiletine and propafenone in human beings.

Background And Objective: Mexiletine and propafenone are often used concomitantly and are metabolized by the same cytochrome P450 isozymes, namely CYP2D6, CYP1A2, and probably CYP3A4. Our objective was to study the potential pharmacokinetic and electrophysiological interactions between mexiletine and propafenone.

Methods: Fifteen healthy volunteers, 8 extensive metabolizers and 7 poor metabolizers of CYP2D6, received oral doses of mexiletine 100 mg two times daily from day 1 to day 8 and oral doses of propafenone 150 mg two times daily from day 5 to day 12.

Hypertriglyceridemic waist: A marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men?

Background: The present study tested the hypothesis that simple variables, such as waist circumference and fasting plasma triglyceride (TG) concentrations, could be used as screening tools for the identification of men characterized by a metabolic triad of nontraditional risk factors (elevated insulin and apolipoprotein [apo] B and small, dense LDL particles).

Methods And Results: Results of the metabolic study (study 1) conducted on 185 healthy men indicate that a large proportion (>80%) of men with waist circumference values >/=90 cm and with elevated TG levels (>/=2.0 mmol/L) were characterized by the atherogenic metabolic triad.

Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity.

The prototype "classic" over-the-counter antihistamine diphenhydramine was shown to interact with the polymorphic P450 enzyme CYP2D6. This project was undertaken to investigate (1) whether diphenhydramine inhibits the biotransformation of the clinically relevant CYP2D6 substrate metoprolol in vitro and (2) whether this in vitro interaction results in a clinically significant pharmacokinetic and pharmacodynamic drug interaction in vivo. In vitro incubations were carried out with microsomes obtained from lymphoblastic cells transfected with CYP2D6 complementary deoxyribonucleic acid to determine the type and extent of inhibition.

Influence of CYP2D6 activity on the disposition and cardiovascular toxicity of the antidepressant agent venlafaxine in humans.

According to in-vitro studies with microsomes from human livers and from yeast expression systems with high CYP2D6 activity, the major oxidation pathway of venlafaxine is catalysed by CYP2D6. In this study, we investigated the role of the CYP2D6 polymorphism and the effects of low-dose quinidine, a selective inhibitor of, CYP2D6, on the disposition of venlafaxine. Fourteen healthy men, eight with the extensive metabolizer and six with the poor metabolizer phenotype were administered venlafaxine hydrochloride 18.