Hemodynamic Effect of Laser Therapy in Spontaneously Hypertensive Rats

Systemic arterial hypertension (SAH) is considered to be the greatest risk factor for the development of neuro-cardiovascular pathologies, thus constituting a severe Public Health issue in the world. The Low-Level Laser Therapy (LLLT), or laser therapy, activates components of the cellular structure, therefore converting luminous energy into photochemical energy and leading to biophysical and biochemical reactions in the mitochondrial respiratory chain. The LLLT promotes cellular and tissue photobiomodulation by means of changes in metabolism, leading to molecular, cellular and systemic changes. The objective of this study was to analyze the action of low-level laser in the hemodynamic modulation of spontaneously hypertensive rats, in the long term. Animals (n = 16) were randomly divided into the Laser Group (n = 8), which received three weekly LLLT irradiations for seven weeks, and into the Sham Group (n = 8), which received three weekly simulations of laser for seven weeks, accounting for 21 applications in each group. After seven weeks, animals were cannulated by the implantation of a catheter in the left carotid artery. On the following day, the systemic arterial pressure was recorded. The Laser Group showed reduced levels of mean blood pressure, with statistically significant reduction (169 ± 4 mmHg* vs. 182 ± 4 mmHg from the Sham Group) and reduced levels of diastolic pressure (143 ± 4 mmHg* vs. 157 ± 3 mmHg from the Sham Group), revealing a 13 and 14 mmHg decrease, respectively. Besides, there was a concomitant important decline in heart rate (312 ± 14 bpm vs. 361 ± 13 bpm from the Sham Group). Therefore, laser therapy was able to produce hemodynamic changes, thus reducing pressure levels in spontaneously hypertensive rats.

Determinants of Functional and Structural Properties of Large Arteries in Healthy Individuals

Background: Changes in the properties of large arteries correlate with higher cardiovascular risk. Recent guidelines have included the assessment of those properties to detect subclinical disease. Establishing reference values for the assessment methods as well as determinants of the arterial parameters and their correlations in healthy individuals is important to stratify patients. Objective: To assess, in healthy adults, the distribution of the values of pulse wave velocity, diameter, intima-media thickness and relative distensibility of the carotid artery, in addition to assessing the demographic and clinical determinants of those parameters and their correlations. Methods: This study evaluated 210 individuals (54% women; mean age, 44 ± 13 years) with no evidence of cardiovascular disease. The carotid-femoral pulse wave velocity was measured with a Complior® device. The functional and structural properties of the carotid artery were assessed by using radiofrequency ultrasound. Results: The means of the following parameters were: pulse wave velocity, 8.7 ± 1.5 m/s; diameter, 6,707.9 ± 861.6 μm; intima-media thickness, 601 ± 131 μm; relative distensibility, 5.3 ± 2.1%. No significant difference related to sex or ethnicity was observed. On multiple linear logistic regression, the factors independently related to the vascular parameters were: pulse wave velocity, to age (p < 0.01) and triglycerides (p = 0.02); intima-media thickness, to age (p < 0.01); diameter, to creatinine (p = 0.03) and age (p = 0.02); relative distensibility, to age (p < 0.01) and systolic and diastolic blood pressures (p = 0.02 and p = 0.01, respectively). Pulse wave velocity showed a positive correlation with intima media thickness (p < 0.01) and with relative distensibility (p < 0.01), while diameter showed a positive correlation with distensibility (p = 0.03). Conclusion: In healthy individuals, age was the major factor related to aortic stiffness, while age and diastolic blood pressure related to the carotid functional measure. The carotid artery structure was directly related to aortic stiffness, which was inversely related to the carotid artery functional property.

Insulin Resistance, Dyslipidemia and Cardiovascular Changes in a Group of Obese Children

Introduction: Obesity-related comorbidities are present in young obese children, providing a platform for early adult cardiovascular disorders. Objectives: To compare and correlate markers of adiposity to metabolic disturbances, vascular and cardiac morphology in a European pediatric obese cohort. Methods: We carried out an observational and transversal analysis in a cohort consisting of 121 obese children of both sexes, between the ages of 6 and 17 years. The control group consisted of 40 children with normal body mass index within the same age range. Markers of adiposity, plasma lipids and lipoproteins, homeostasis model assessment-insulin resistance, common carotid artery intima-media thickness and left ventricular diameters were analyzed. Results: There were statistically significant differences between the control and obese groups for the variables analyzed, all higher in the obese group, except for age, high-density lipoprotein cholesterol and adiponectin, higher in the control group. In the obese group, body mass index was directly correlated to left ventricular mass (r=0.542; p=0.001), the homeostasis model assessment-insulin resistance (r=0.378; p=<0.001) and mean common carotid artery intima-media thickness (r=0.378; p=<0.001). In that same group, insulin resistance was present in 38.1%, 12.5% had a combined dyslipidemic pattern, and eccentric hypertrophy was the most common left ventricular geometric pattern. Conclusions: These results suggest that these markers may be used in clinical practice to stratify cardiovascular risk, as well as to assess the impact of weight control programs.

Assessment of Intima-Media Thickness in Healthy Children Aged 1 to 15 Years

Abstract Background: Carotid intima-media thickness (CIMT) has been shown to be increased in children and adolescents with traditional cardiovascular risk factors such as obesity, hypertension, and chronic kidney disease, compared with those of healthy children. Objective: To assess the influence of sex, age and body mass index (BMI) on the CIMT in healthy children and adolescents aged 1 to 15 years. Methods: A total of 280 healthy children and adolescents (males, n=175; mean age, 7.49±3.57 years; mean BMI, 17.94±4.1 kg/m2) were screened for CIMT assessment. They were divided into 3 groups according to age: GI, 1 to 5 years [n=93 (33.2%); males, 57; mean BMI, 16±3 kg/m2]; GII, 6 to 10 years [n=127 (45.4%); males, 78; mean BMI, 17.9±3.7 kg/m2], and GIII, 11 to 15 years [n=60 (21.4%); males, 40; mean BMI, 20.9±4.5 kg/m2]. Results: There was no significant difference in CIMT values between male and female children and adolescents (0.43±0.06 mm vs. 0.42±0.05 mm, respectively; p=0.243). CIMT correlated with BMI neither in the total population nor in the 3 age groups according to Pearson correlation coefficient. Subjects aged 11 to 15 years had the highest CIMT values (GI vs. GII, p=0.615; GI vs. GIII, p=0.02; GII vs. GIII, p=0.004). Conclusions: CIMT is constant in healthy children younger than 10 years, regardless of sex or BMI. CIMT increases after the age of 10 years.

Anatomical landmarks for transnasal endoscopic skull base surgery.

Resection of midline skull base lesions involve approaches needing extensive neurovascular manipulation. Transnasal endoscopic approach (TEA) is minimally invasive and ideal for certain selected lesions of the anterior skull base. A thorough knowledge of endonasal endoscopic anatomy is essential to be well versed with its surgical applications and this is possible only by dedicated cadaveric dissections. The goal in this study was to understand endoscopic anatomy of the orbital apex, petrous apex and the pterygopalatine fossa. Six cadaveric heads (3 injected and 3 non injected) and 12 sides, were dissected using a TEA outlining systematically, the steps of surgical dissection and the landmarks encountered. Dissection done by the "2 nostril, 4 hands" technique, allows better transnasal instrumentation with two surgeons working in unison with each other. The main surgical landmarks for the orbital apex are the carotid artery protuberance in the lateral sphenoid wall, optic nerve canal, lateral optico-carotid recess, optic strut and the V2 nerve. Orbital apex includes structures passing through the superior and inferior orbital fissure and the optic nerve canal. Vidian nerve canal and the V2 are important landmarks for the petrous apex. Identification of the sphenopalatine artery, V2 and foramen rotundum are important during dissection of the pterygopalatine fossa. In conclusion, the major potential advantage of TEA to the skull base is that it provides a direct anatomical route to the lesion without traversing any major neurovascular structures, as against the open transcranial approaches which involve more neurovascular manipulation and brain retraction. Obviously, these approaches require close cooperation and collaboration between otorhinolaryngologists and neurosurgeons.

Extracorporeal membrane oxygenation support after heart explantation: a proposal on how to deal with hyperacute rejection of heart transplant

Purpose: In extreme situations, such as hyperacute rejection of heart transplant or major bleeding per-operating complications, an urgent heart explantation might be the only means of survival. The aim of this experimental study was to improve the surgical technique and the hemodynamics of an Extracorporeal Membrane Oxygenation (ECMO) support through a peripheral vascular access in an acardia model. Methods: An ECMO support was established in 7 bovine experiments (59±6.1 kg) by the transjugular insertion to the caval axis of a self-expanded cannula, with return through a carotid artery. After baseline measurements of pump flow and arterial and central venous pressure, ventricular fibrillation was induced (B), the great arteries were clamped, the heart was excised and right and left atria remnants, containing the pulmonary veins, were sutured together leaving an atrial septal defect (ASD) over the cannula in the caval axis. Measurements were taken with the pulmonary artery (PA) clamped (C) and anastomosed with the caval axis (D). Regular arterial and central venous blood gases tests were performed. The ANOVA test for repeated measures was used to test the null hypothesis and a Bonferroni t method for assessing the significance in the between groups pairwise comparison of mean pump flow. Results: Initial pump flow (A) was 4.3±0.6 L/min dropping to 2.8±0.7 L/min (P B-A= 0.003) 10 minutes after induction of ventricular fibrillation (B). After cardiectomy, with the pulmonary artery clamped (C) it augmented not significantly to 3.5±0.8 L/min (P C-B= 0.33, P C-A= 0.029). Finally, PA anastomosis to the caval axis was followed by an almost to baseline pump flow augmentation (4.1±0.7 L/min, P D-B= 0.009, P D-C= 0.006, P D-A= 0.597), permitting a full ECMO support in acardia by a peripheral vascular access. Conclusions: ECMO support in acardia is feasible, providing new opportunities in situations where heart must urgently be explanted, as in hyperacute rejection of heart transplant. Adequate drainage of pulmonary circulation is pivotal in order to avoid pulmonary congestion and loss of volume from the normal right to left shunt of bronchial vessels. Furthermore, the PA anastomosis to the caval axis not only improves pump flow but it also permits an ECMO support by a peripheral vascular access and the closure of the chest.

Evidence for a role of sphingosine-1 phosphate in cardiovascular remodelling in Fabry disease.

AIMS: A hallmark of Fabry disease is the concomitant development of left-ventricular hypertrophy and arterial intima-media thickening, the pathogenesis of which is thought to be related to the presence of a plasmatic circulating growth-promoting factor. We therefore characterized the plasma of patients with Fabry disease in order to identify this factor. METHODS AND RESULTS: Using a classical biochemical strategy, we isolated and identified sphingosine-1 phosphate (S1P) as a proliferative factor present in the plasma of patients with Fabry disease. Plasma S1P levels were significantly higher in 17 patients with Fabry disease compared with 17 healthy controls (225 +/- 40 vs. 164 +/- 17 ng/mL; P = 0.005). There was a positive correlation between plasma S1P levels and both common carotid artery intima-media thickness and left-ventricular mass index (r(2) = 0.47; P = 0.006 and r(2) = 0.53; P = 0.0007, respectively). In an experimental model, mice treated with S1P developed cardiovascular remodelling similar to that observed in patients with Fabry disease. CONCLUSION: Sphingosine-1 phosphate participates in cardiovascular remodelling in Fabry disease. Our findings have implications for the treatment of cardiovascular involvement in Fabry disease.

Decreased compliance on arterial anastomoses.

The present study was undertaken to examine the cross-sectional vascular compliance at the anastomotic site. METHODS AND MATERIAL: We performed end-to-end anastomosis on the carotid artery of six pigs using continuous 6/0 polypropylene. Four carotid arteries were excised and mounted in a perfusion chamber while the remaining two were left in living animals. We used pulsed ultrasound (NIUS 02) to generate detailed longitudinal profiles of diameter and compliance in the proximity and on the anastomosis. RESULTS: On the anastomosis, the vessel diameter decreases (-1 to -2.6% of diastolic diameter) when blood pressure increases with an exponential correlation (R2 = 0.75). The arterial compliance at the anastomosis was negative: the vessel cross-section reduction for a pulse pressure of 1 up to 32 mmHg was 0.9 to 2% of diastolic vessel cross-section. CONCLUSIONS: Vessel movement generated a dynamic stenosis whose magnitude seems to depend on blood pressure level. Increasing blood pressure causes the retraction of vessel ends which causes vessel lumen reduction. These results suggest that continuous suture does not provide the continuity of mechanical properties of the artery.

Enhancement of autophagic flux after neonatal cerebral hypoxia-ischemia and its region-specific relationship to apoptotic mechanisms.

The multiplicity of cell death mechanisms induced by neonatal hypoxia-ischemia makes neuroprotective treatment against neonatal asphyxia more difficult to achieve. Whereas the roles of apoptosis and necrosis in such conditions have been studied intensively, the implication of autophagic cell death has only recently been considered. Here, we used the most clinically relevant rodent model of perinatal asphyxia to investigate the involvement of autophagy in hypoxic-ischemic brain injury. Seven-day-old rats underwent permanent ligation of the right common carotid artery, followed by 2 hours of hypoxia. This condition not only increased autophagosomal abundance (increase in microtubule-associated protein 1 light chain 3-11 level and punctuate labeling) but also lysosomal activities (cathepsin D, acid phosphatase, and beta-N-acetylhexosaminidase) in cortical and hippocampal CA3-damaged neurons at 6 and 24 hours, demonstrating an increase in the autophagic flux. In the cortex, this enhanced autophagy may be related to apoptosis since some neurons presenting a high level of autophagy also expressed apoptotic features, including cleaved caspase-3. On the other hand, enhanced autophagy in CA3 was associated with a more purely autophagic cell death phenotype. In striking contrast to CA3 neurons, those in CA1 presented only a minimal increase in autophagy but strong apoptotic characteristics. These results suggest a role of enhanced autophagy in delayed neuronal death after severe hypoxia-ischemia that is differentially linked to apoptosis according to the cerebral region.

Lufaxin, a novel factor Xa inhibitor from the salivary gland of the sand fly Lutzomyia longipalpis blocks protease-activated receptor 2 activation and inhibits inflammation and thrombosis in vivo.

OBJECTIVE: Blood-sucking arthropods' salivary glands contain a remarkable diversity of antihemostatics. The aim of the present study was to identify the unique salivary anticoagulant of the sand fly Lutzomyia longipalpis, which remained elusive for decades. METHODS AND RESULTS: Several L. longipalpis salivary proteins were expressed in human embryonic kidney 293 cells and screened for inhibition of blood coagulation. A novel 32.4-kDa molecule, named Lufaxin, was identified as a slow, tight, noncompetitive, and reversible inhibitor of factor Xa (FXa). Notably, Lufaxin's primary sequence does not share similarity to any physiological or salivary inhibitors of coagulation reported to date. Lufaxin is specific for FXa and does not interact with FX, Dansyl-Glu-Gly-Arg-FXa, or 15 other enzymes. In addition, Lufaxin blocks prothrombinase and increases both prothrombin time and activated partial thromboplastin time. Surface plasmon resonance experiments revealed that FXa binds Lufaxin with an equilibrium constant ≈3 nM, and isothermal titration calorimetry determined a stoichiometry of 1:1. Lufaxin also prevents protease-activated receptor 2 activation by FXa in the MDA-MB-231 cell line and abrogates edema formation triggered by injection of FXa in the paw of mice. Moreover, Lufaxin prevents FeCl(3)-induced carotid artery thrombus formation and prolongs activated partial thromboplastin time ex vivo, implying that it works as an anticoagulant in vivo. Finally, salivary gland of sand flies was found to inhibit FXa and to interact with the enzyme. CONCLUSIONS: Lufaxin belongs to a novel family of slow-tight FXa inhibitors, which display antithrombotic and anti-inflammatory activities. It is a useful tool to understand FXa structural features and its role in prohemostatic and proinflammatory events.

Is the GraftConnector a valid alternative to running suture in end-to-side coronary arteries anastomoses?

BACKGROUND: An animal study was carried out to compare long-term patency rates of coronary anastomoses performed with the GraftConnector versus running suture technique. METHODS: 10 sheep, 45 to 55 kg, underwent off-pump coronary artery bypass grafting (right internal mammary artery to left anterior descending artery). In 5 animals, the anastomosis was performed with a GraftConnector and in 5 animals with 7-0 running suture. Intraoperative fluoroscopy and a fluoroscopic control at 6 months were performed. After 6 months, the animals were sacrificed and the anastomoses were examined histologically. RESULTS: All animals survived at 6 months with 100% anastomosis patency rates in both groups. In the GraftConnector group, the anastomosis diameter at 6 months fluoroscopy was 118% of native left anterior descending artery versus 97% of the control group. Luminal anastomotic width at histology was 1.7 +/- 0.2 mm in the device group versus 1.6 +/- 0.1 mm in the control group. Mean intimal hyperplasia thickness was 0.21 +/- 0.1 mm in the device group versus 0.01 mm in the control group. CONCLUSIONS: The GraftConnector provides a consistent and reproducible coronary artery anastomosis and reduces technical demand and manual dexterity in coronary operations. Long-term results demonstrate that off-pump coronary artery bypass grafting performed with the GraftConnector had the same patency rate and luminal width as those performed with running suture.

A simple way to decompress the left ventricle during venoarterial bypass

OBJECTIVE: The aim of this investigation was to improve the hemodynamics during venoarterial bypass by remote decompression of the left ventricle (LV). METHODS: Venoarterial bypass was established in 5 bovine experiments (69+/-10 kg) by the transjugular insertion of a self-expanding cannula (smartcanula) with return through a carotid artery. Cardiogenic shock was simulated with ventricular fibrillation induced by an external stimulator. Left ventricular decompression was achieved by switching to transfemoral drainage of the pulmonary artery (PA) with a long self-expanding cannula. RESULTS: Initial pump flow was 4.7+/-0.9 l/min and the aortic pressure accounted for 75+/-21 mmHg. After induction of ventricular fibrillation, the pump flow dropped after 11+/-8 min to 2.5+/-0.1 l/min. Transfemoral decompression increased the pump flow to 5.6+/-0.7 l/min, while the RV pressure decreased from 27+/-9 to 3+/-5 mmHg, the PA pressure decreased from 29+/-7 to 5+/-4 mmHg, the LV pressure decreased from 29+/-6 to 7+/-2 mmHg, and the aortic pressure increased from 31+/-3 to 47+/-11 mmHg. CONCLUSIONS: Remote drainage of the pulmonary artery during venoarterial bypass allows for effective decompression of the left ventricle and provides superior hemodynamics.

Regulation of the vascular gap junctions in a mouse model of intimal hyperplasia

Objective: Intimal hyperplasia (IH) is one of the leading causes of failure¦after vascular interventions. It involves the proliferation of smooth muscle¦cells (SMCs) and the production of extracellular fibrous matrix. Gap junctional¦communication, mediated by membrane connexins (Cx), participates to the¦control of proliferation and migration. In human and mice vessels, endothelial¦cells (ECs) express Cx37, Cx40 and Cx43, whereas SMCs are coupled by Cx43.¦We previously reported that Cx43 was increased in the SMCs of a human vein¦during the development of IH.¦In our experimental model of mice carotid artery ligation (CAL), luminal¦narrowing occurred by SMCs-rich neointima after 2-4 weeks of ligation.¦This experimental model of mice allows us to decipher the regulation of the¦cardiovascular connexins in the mouse.¦Methods: C57BL/6 mice were anesthetized and the left common carotid artery¦was dissected through a neck incision and ligated near the carotid bifurcation.¦The mice were then euthanized at 7, 14 and 28 days. Morphometric analyses¦were then performed with measurements of total area, lumen and intimal area¦and media thickness. Western blots, immunocytochemistry and quantitative¦RT-PCR were performed for Cx43, Cx40 and Cx37.¦Results: All animals recovered with no symptom of stroke. Morphometric¦analysis demonstrated that carotid ligation resulted in an initial increase (after¦7 days) of the total vessel area followed by its reduction (after 28 days). This¦phenomena was associated with a progressive increase in the intimal area and a¦consecutive decrease of the lumen. The media thickness was also increased after¦14 and 28 days. This neointima formation was associated to a marked increase¦in the expression of Cx43 at both protein and RNA levels. Concomitantly,¦Cx40 and Cx37 protein expression were reduced in the endothelium. This was¦confirmed by en face analyses showing reduced Cx37 and Cx40 levels in the¦endothelial cells covering the lesion.¦Conclusion: This study assessed the regulation of the cardiovascular connexins¦in the development of IH. This model will allow us to characterize the¦involvement of gap junctions in the IH. In turn, this understanding is¦instrumental for the development of new therapeutical tools, as well as for¦the evaluation of the effects of drugs and gene therapies of this disease for which¦there is no efficient therapy available.

Prévention primaire et dépistage chez l'adulte: mise a jour 2014 [Primary prevention and screening in adults: update 2014].

Cet article propose une mise à jour des recommandations pour le bilan de santé et la prévention primaire et secondaire de nombreuses maladies cardiovasculaires et oncologiques. Les nouveautés pour le dépistage des cancers concernent essentiellement les cancers colorectal, du poumon et de la prostate. Pour la prévention des maladies cardiovasculaires, le dépistage de la sténose de l'artère carotidienne n'est toujours pas recommandé. Les preuves de la littérature sont insuffisantes pour recommander le dépistage de l'artériopathie coronarienne ou périphérique chez les patients asymptomatiques. Le partage de l'information et de la décision entre le médecin et le patient est à privilégier lorsqu'il existe une incertitude quant à l'efficacité d'une intervention. This article provides an update on the recommendations for the routine check-up and the primary and secondary prevention of cancer and cardiovascular disease. Changes for cancer screening affect mainly colorectal, lung and prostate cancers. In the area of cardiovascular disease prevention, screening for carotid artery stenosis is still not recommended. The current evidence is insufficient to recommend screening for coronary heart disease or peripheral artery disease in asymptomatic patients. Shared information and decision making between physician and patient is recommended when there is uncertainty regarding the effectiveness of an intervention.

Alterations of specific biomarkers of metabolic pathways in vascular tree from patients with Type 2 diabetes.

The aims of this study were to check whether different biomarkers of inflammatory, apoptotic, immunological or lipid pathways had altered their expression in the occluded popliteal artery (OPA) compared with the internal mammary artery (IMA) and femoral vein (FV) and to examine whether glycemic control influenced the expression of these genes. The study included 20 patients with advanced atherosclerosis and type 2 diabetes mellitus, 15 of whom had peripheral arterial occlusive disease (PAOD), from whom samples of OPA and FV were collected. PAOD patients were classified based on their HbA1c as well (HbA1c ≤ 6.5) or poorly (HbA1c > 6.5) controlled patients. Controls for arteries without atherosclerosis comprised 5 IMA from patients with ischemic cardiomyopathy (ICM). mRNA, protein expression and histological studies were analyzed in IMA, OPA and FV. After analyzing 46 genes, OPA showed higher expression levels than IMA or FV for genes involved in thrombosis (F3), apoptosis (MMP2, MMP9, TIMP1 and TIM3), lipid metabolism (LRP1 and NDUFA), immune response (TLR2) and monocytes adhesion (CD83). Remarkably, MMP-9 expression was lower in OPA from well-controlled patients. In FV from diabetic patients with HbA1c ≤6.5, gene expression levels of BCL2, CDKN1A, COX2, NDUFA and SREBP2 were higher than in FV from those with HbA1c >6.5. The atherosclerotic process in OPA from diabetic patients was associated with high expression levels of inflammatory, lipid metabolism and apoptotic biomarkers. The degree of glycemic control was associated with gene expression markers of apoptosis, lipid metabolism and antioxidants in FV. However, the effect of glycemic control on pro-atherosclerotic gene expression was very low in arteries with established atherosclerosis.