Triple vasopeptidase inhibition of angiotensin-converting enzyme/neutral endopeptidase/endothelin-converting enzyme activities on the hemodynamic profile of chronically instrumented unrestrained conscious spontaneously hypertensive rats.

Inhibition of the renin-angiotensin system with an angiotensin-converting enzyme inhibitor (ACEi) is an effective therapy in hypertension. Vasopeptidase inhibition was initially proposed with compounds inhibiting both angiotensin-converting enzyme and neutral endopeptidase (omapatrilat), but clinical trials revealed that reducing angiotensin II while blocking the degradation of vasodilatory peptides was not without concerns. We have previously investigated the combination of an ACEi with an endothelin-converting enzyme inhibitor (ECEi); now we add a neutral endopeptidase inhibitor (NEPi) toward triple vasopeptidase inhibition.

Role of the endothelin system in secondary pulmonary hypertension related to air embolism: lessons learned from testing four classes of endothelin blockers in a rat model.

A rat model of acute pulmonary air embolism (APAE) was developed. These animals had a higher right ventricular systolic pressure (RVSP) (+ 69% at 15-minute peak, and 21-34% at 30-180 minutes), as well as a reduced mean arterial blood pressure (10-20% at 60-180 minutes), heart rate (20-26% at 60-180 minutes) and PaO2 (9-11% at 30-180 minutes) compared with control rats. The role of the endothelin (ET) system, known to be involved in pulmonary hypertension of various etiologies, was investigated by evaluating the effect of the four classes of ET blockers: ET-converting enzyme inhibitor (ECEi) (CGS 35066), selective endothelin-A receptor antagonist (ETA-Ra) (Atrasentan, ABT-627), endothelin-B receptor antagonist (ETB-Ra) (A-192621) or mixed endothelin-A/endothelin-B receptor antagonist (ETA/B-Ra) (A-182086) in this animal model.

Impact of valve prosthesis-patient mismatch on pulmonary arterial pressure after mitral valve replacement.

Objectives: We sought to determine the impact of valve prosthesis-patient mismatch (PPM) on pulmonary arterial (PA) pressure after mitral valve replacement (MVR).

Background: Pulmonary arterial hypertension is a serious complication of mitral valve disease, and it is a major risk factor for poor outcome after MVR. We hypothesized that valve PPM might be a determinant of PA hypertension after MVR.

Aortic valve-sparing procedure with cusp elongation and free edge reinforcement for bicuspid aortic valve.

Aortic valve-sparing procedures demonstrate excellent valvular function at midterm. Recently authors have reported acceptable early results with aortic valve-sparing procedures on patients with regurgitant bicuspid valves. We report the case of a novel procedure to preserve bicuspid valves with a calcified raphe and root dilatation.

Contribution of bariatric surgery to the comprehension of morbid obesity.

Convinced that morbid obesity was not due to food excess but rather to a metabolic disorder, we searched in the literature for data in favor of a metabolic disorder. We have found evidence in support of the thesis that the cause of morbid obesity is the inability to burn excessive caloric intake normally. It would involve the difficulty to increase heat with the amount of calories taken, which would be faulty and force fat deposition.

Hypolipidemic action of the SERM acolbifene is associated with decreased liver MTP and increased SR-BI and LDL receptors.

This study aimed to identify the mechanisms of the hypolipidemic action of the selective estrogen receptor modulator (SERM) acolbifene (ACOL). Four weeks of treatment with ACOL reduced fasting and postprandial plasma triglycerides (TGs), an effect associated with lower VLDL-TG secretion rate (-25%), and decreased mRNA of microsomal triglyceride transfer protein (MTP; -29%). ACOL increased liver TG concentration (+100%) and amplified the feeding-induced increase in the master lipogenic regulators sterol-regulatory element binding protein-1a (SREBP-1a) and SREBP-1c.

Changing trends in management of thoracic aortic disease: where do we stand with thoracic endovascular stent grafts?

Background: Descending thoracic aortic surgery is linked to a high morbidity and mortality. Thoracic endovascular stent grafts were designed to decrease perioperative risks, especially in patients with severe comorbidities. However, procedure-related complications and clinical outcomes remain ill-defined.

Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine coadministration during exercise testing in healthy premenopausal women.

Premenopausal women may be most vulnerable to acute coronary syndromes at a point in their menstrual cycle when their plasma estrogen levels are the lowest during and immediately after menstruation. Metoprolol is a first-line drug in the management of patients with acute coronary syndrome; however, when metoprolol was marketed in 1982, women were largely excluded from clinical trials. Furthermore, the over-the-counter antihistamine diphenhydramine inhibited the metabolism of the CYP2D6 substrate metoprolol in healthy, young men with pharmacokinetic and pharmacodynamic consequences.

Molecular links between aging and adipose tissue.

White adipose tissue now emerges as a pivotal organ controlling lifespan. Calorie restriction, which so far extends lifespan in all organisms, primarily affects energy stores in adipose tissue. Genetic manipulations aiming at modifying fat mass also impact on the duration of life in several model organisms.

Impact of systemic hypertension on the assessment of aortic stenosis.

Objective: To determine the effect of systemic arterial hypertension on the indices of aortic stenosis (AS) severity.

Methods: A severe supravalvar AS was created in 24 pigs. The maximum and mean pressure gradients across the stenosis were measured by Doppler echocardiography and by catheterisation.

Fluctuating inflammatory markers in patients with stable ischemic heart disease.

Background: C-reactive protein (CRP), a marker of inflammation, is increasingly measured to stratify coronary artery disease risk and guide clinical management. However, little is known about how inflammatory markers fluctuate over time in patients with stable ischemic heart disease.

Methods: We examined serial serum CRP values in 159 patients with histories spanning the clinical spectrum of ischemic heart disease.

Impact of waist circumference on the relationship between blood pressure and insulin: the Quebec Health Survey.

Hyperinsulinemia has been suggested to be involved in the etiology of obesity-associated hypertension. The objective of the present study was to quantify, in a population-based study, the respective contributions of excess adiposity (body mass index [BMI]), waist circumference (WC), fasting insulin levels, and insulin sensitivity to the variation of resting blood pressure. The Quebec Health Survey was used to obtain fasting plasma insulin and glucose levels and resting blood pressure as well as anthropometric measurements in a representative sample of 907 men and 937 women.

Role of arginine residues on the S4 segment of the Bacillus halodurans Na+ channel in voltage-sensing.

The one-domain voltage-gated sodium channel of Bacillus halodurans (NaChBac) is composed of six transmembrane segments (S1-S6) comprising a pore-forming region flanked by segments S5 and S6 and a voltage-sensing element composed of segment S4. To investigate the role of the S4 segment in NaChBac channel activation, we used the cysteine mutagenesis approach where the positive charges of single and multiple arginine (R) residues of the S4 segment were replaced by the neutrally charged amino acid cysteine (C). To determine whether it was the arginine residue itself or its positive charge that was involved in channel activation, arginine to lysine (R to K) mutations were constructed.

Anginal threshold between stress tests: exercise versus dobutamine stress echocardiography.

Purpose: Dobutamine echocardiography (DOB) can be substituted to exercise testing when necessary for clinical reasons. Current literature suggests DOB is maximal when 85% of maximal predicted heart rate (%PHR) is achieved (similar to EX), but there is little evidence to determine whether this target has the same clinical significance as during EX. We therefore performed this study to compare the ischemic threshold between EX and DOB.

Very late in-stent restenosis (five years) presenting as an ST elevation acute myocardial infarction.

Late in-stent restenosis is a rare event. The present report discusses the case of a patient who presented with an acute inferior myocardial infarction five years after stent implantation in the distal right coronary artery. Urgent angiography revealed an occluded right coronary artery in the middle portion of the stented segment.

Asthma and sleep apnea in patients with morbid obesity: outcome after bariatric surgery.

Background: Asthma and sleep apnea syndrome (SAS) are frequently reported in obese patients. The authors determined the prevalence of asthma and SAS in morbidly obese patients and the effect of biliopancreatic diversion with duodenal switch (BPD-DS) on these conditions.

Methods: 398 patients were evaluated for bariatric surgery in a university-affiliated tertiary care center.

Effect of type 2 diabetes on various electrophoretic characteristics of low-density lipoprotein particles in women.

Aims/hypothesis: Coronary heart disease represents the leading cause of death in type 2 diabetic patients. As the small, dense LDL phenotype is a typical feature of the dyslipidaemic state found in type 2 diabetes, this characteristic could be an important mediator of the elevated coronary heart disease risk in this condition. We have therefore studied the effect of type 2 diabetes on various electrophoretic characteristics of LDL particles.

Adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein and lipid levels in men.

The present study examined the associations between a major adipokine, adiponectin, and adiposity indices as well as metabolic risk variables in a sample of 190 untreated asymptomatic men. Anthropometric measurements and a complete fasting plasma lipoprotein and lipid profile were obtained, and subjects underwent an oral glucose tolerance test. Fasting plasma adiponectin concentrations were determined by an ELISA.

Incidence of stent under-deployment as a cause of in-stent restenosis in long stents.

Although stent under-deployment (SU) has been associated with increased risk of in-stent restenosis, little data have been reported on the incidence of SU in patients presenting with clinical in-stent restenosis. In 59 patients referred for vascular brachytherapy and showing angiographic in-stent restenosis, we sought (1) to determine the incidence of SU using standard intravascular ultrasound (IVUS) criteria (2) to evaluate the effects of repeat angioplasty on further stent expansion. Stented length was 32+/-17 mm and diameter stenosis was 75+/-14%.

Role of fibric acid derivatives in the management of risk factors for coronary heart disease.

Although elevated low-density lipoprotein (LDL)-cholesterol is a well established coronary heart disease (CHD) risk factor, the ability to adequately discriminate high-risk individuals by this risk factor alone is limited and other metabolic risk variables are known to modulate CHD risk. For instance, it has been reported that the cluster of metabolic disturbances observed among individuals with abdominal obesity, the so-called metabolic syndrome, is associated with a substantially increased risk of CHD. Among the features of the dyslipidaemic profile observed in these individuals, the high triglyceride-low high-density lipoprotein (HDL)-cholesterol dyslipidaemia is predictive of an elevated risk of CHD.

Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with Brugada syndrome.

The SCN5A gene encodes the alpha subunit of the human cardiac voltage-gated sodium channel. Mutations in SCN5A are responsible for Brugada syndrome, an inherited cardiac disease that leads to idiopathic ventricular fibrillation (IVF) and sudden death. In this study, we screened nine individuals from a single family and 12 sporadic patients who were clinically diagnosed with Brugada syndrome.