LEAD AND CADMIUM SUBCHRONIC INTOXICATION IN RATS AS A FACTOR OF DAMAGE TO THE CARDIOVASCULAR SYSTEM

Lead-cadmium intoxication is an occupational risk factor for copper-smelting industry workers. People inhabiting the areas near the copper plants are also at risk. Subchronic intoxication was modeled by repeated intraperitoneal injections of lead acetate and cadmium chloride both in isolation and in combination, 3 times a week for 6 weeks. A heart rate decrease in animals with Cd intoxication and a blood flow velocity decrease in those with Pb intoxication have been found. The impact of Pb and Cd on blood pressure proved to be contra-directional. ECG analysis revealed a prolonged duration of QRS in Cd intoxication, a prolonged QT interval and a baseline lowering in Pb+Cd intoxication. A variety of changes has been found with respect to the diameter of cardiomyocytes and the thickness of aortic wall layers in Pb and/or Cd intoxication. Any toxic exposure resulted in the decrease in number of nuclei per unit area of myocardium histological preparation.

Endothelial-protective effects of a G-protein-biased sphingosine-1 phosphate receptor-1 agonist, SAR247799, in type-2 diabetes rats and a randomized placebo-controlled patient trial.

SAR247799 is a G-protein-biased sphingosine-1 phosphate receptor-1 (S1P1) agonist designed to activate endothelial S1P1 and provide endothelial-protective properties, while limiting S1P1 desensitization and consequent lymphocyte-count reduction associated with higher doses. A dose-response study in diabetic rats with 5-week SAR247799 treatment demonstrated, at sub-lymphocyte-reducing doses, renal function and endothelial biomarker improvements and was used to select doses for human investigation. Type-2 diabetes patients, enriched for endothelial dysfunction (flow-mediated dilation, FMD<7%) (n=54), were randomized, in two sequential cohorts, to 28-day once-daily treatment with SAR247799 (1 or 5 mg in ascending cohorts), placebo or 50 mg sildenafil (positive control) in a 5:2:2 ratio per cohort. The maximum FMD change from baseline versus placebo for all treatments was reached on day 35; mean differences versus placebo were 0.60% (95% CI -0.34%-1.53%; p=0.203) for 1 mg SAR247799, 1.07% (95% CI 0.13%-2.01%; p=0.026) for 5 mg SAR247799 and 0.88% (95% CI -0.15%-1.91%; p=0.093) for 50 mg sildenafil. Both doses of SAR247799 were well tolerated, did not affect blood pressure, and were associated with minimal-to-no lymphocyte reduction and small-to-moderate heart rate decrease. These data provide the first human evidence for endothelial-protective properties of S1P1 activation, with SAR247799 being at least as effective as the clinical benchmark, sildenafil.

Intermittent vagus nerve stimulation allows preventing the “escape” effect of heart rhythm changes

Background.Vagus nerve stimulation has been proposed for the treatment of a number of diseases. The positive effects of vagus nerve stimulation on ischemic and reperfusion myocardial injury has been tested in experimental models. However, the escape effect of vagus activation on heart rate and the methodology to overcome this effect have not been reported properly.Objective. The purpose of the study is to evaluate parameters of prolonged stimulation that decrease heart rate and allow overcoming the escape effect of vagus nerve activation.Design and methods. We used Wistar rats (n = 9). Cervical section was performed under general anesthesia. Left vagus nerve isolated from adjacent tissue was contacted with custom stimulation electrodes and a custom pulse generator. Blood pressure was measured in the right common carotid artery. Limb electrocardiogram was continuously recorded. First, stimulation parameters repeatedly evoking vagal reaction (decrease in heart rate) without nerve damage were evaluated. Second, parameters of intermittent stimulation that allowed repeat and consistent heart rate decrease were assessed.Results. During experiments, in 5 animals the following parameters leading to sustained 30 ± 20 % heart rate reduction were found: rectangular pulse, 30 Hz, 0,5 ms, 1–2 V (0,6– 0,8 mA). Stimulation with 50 Hz frequency led to nerve damage in 1 case. Stimulation with 20 Hz frequency led to heart rate over-suppression of heart rate and blood pressure. Intermittent nerve stimulation was tested in 4 animals and led to repeated heart rate decrease by 38 ± 15 %. The parameters which helped to avoid escape effect on heart rate change were the following: the length of stimulation episode of 45 s and interruption of stimulation for 15 s.Conclusion. Intermittent electrical stimulation evokes vagal reactions on heart rate and allows overcoming the escape effect of vagal activation.

The use of audiovisual distraction eyeglasses as a resource in Pediatric dental care: a case series

ABSTRACT Objective: This study aimed to report a case series on the use of audiovisual distraction eyeglasses in children during dental care. Methods: The influence of the distraction tool on the children’s heart rate frequency and dental care experience was further investigated. The study children had their heart rate recorded during three clinical appointments and underwent the following procedures: 1) anamnesis; 2) modified atraumatic restorative treatment with the child wearing audiovisual eyeglasses; and 3) modified atraumatic restorative treatment without the use of audiovisual eyeglasses. The interval between appointments was up to one week. The heart rate was measured using a pulse oximeter, and a post-treatment questionnaire was applied after the three appointments. The sample consisted of five children aged 4 to 7 years attending the Pediatric Dental Clinics of the State University of Paraíba. Results: While wearing the audiovisual eyeglasses, the children’s individual heart rates were lower in the second dental visit as compared to the first and third ones. The post-treatment questionnaire revealed a preference for the use of audiovisual distraction eyeglasses as the children felt more comfortable, pleased, and had a reduced pain perception and anxiety. Conclusion: The heart rate decrease observed herein suggests that audiovisual eyeglasses may contribute to reducing anxiety during dental care.

Valsalva maneuver techniques for supraventricular tachycardias: Which and how?

Study objective: While some research has been done on Valsalva maneuvers in treating supraventricular tachycardia, there is no standardized algorithm on which technique has been the most effective for the termination of supraventricular tachycardias. In this study, we compare different Valsalva maneuver techniques in order to determine the exact technique needed for maximal vagal response. Methods: This was a repeated measures clinical study, which enlisted a sample of healthy adult volunteers. Participants performed four different Valsalva maneuver techniques (40 mm Hg—10 s, 40 mm Hg—15 s, 50 mm Hg—10 s, and 50 mm Hg—15 s) while lying in a supine position. The maneuvers were repeated three times. An electrocardiography printout was obtained during each trial, and heart rate differences between pre-maneuver and post-maneuver were measured. Results: Among the 97 volunteers who participated in the study, 7 were excluded because the target Valsalva maneuver pressures were not reached, and 1 volunteer was excluded due to T-wave inversion that developed after Valsalva maneuver. We enrolled 89 participants. There was no significant difference in the heart rate decrease among the four techniques. In addition, there was no difference between the vagal responses in terms of age, gender, and body mass index. Conclusion: This study shows that the four different Valsalva maneuver techniques were not superior to one another in terms of decreased heart rate.

In utero testosterone exposure influences physiological responses to dyadic interactions in neurotypical adults

ObjectiveWe investigated how different levels of prenatal exposure to testosterone influence physiological reactions to dyadic interactions, hypothesising that higher levels of prenatal testosterone are linked to greater physiological responses.MethodAutonomic nervous system responses to dyadic interactions focussed on social or physical norms were measured. Physiological assessment of excitability (heart rate, facial temperature) and a behavioural assessment (Likert items judgements) were run on 25 neurotypical participants who had distinct testosterone exposure levels in utero. In utero exposure to testosterone was assessed measuring 2D : 4D (ratio between the lengths of the index and the ring fingers).ResultsHigher testosterone exposure participants showed greater physiological arousal: a greater heart rate decrease, independent from scenario type (p<0.05), and opposite facial temperature changes in response to social (increase) (vs.) physical scenarios (decrease) were found (Left-cheek: p<0.05; Right-cheek: p<0.05).ConclusionThese findings suggest a long-term influence of prenatal environment on adults’ physiological responses during social situations.

Abstract 12420: Ivabradine Effectiveness in Everyday Clinical Practice: Results From a Population With Stable Coronary Artery Disease and Coronary Stenosis (>50%) Not Submitted for Revascularization

Introduction: Angina pectoris is the most common manifestation of flow limited coronary stenosis, reflecting myocardial ischemia and limiting significantly ordinary activities of patients. Purpose: To evaluate Ivabradine’s anti-anginal effectiveness and effect on quality of life (QoL), when co-administered with a β-blocker, during a 4 month therapy of patients with coronary artery disease (CAD) and coronary stenosis (>50%) not submitted for revascularization. Methods: This is a post hoc analysis (563 patients with documented coronary stenosis >50%) of a Pan-Hellenic, prospective, non-interventional study including 2403 patients with CAD and stable angina. Follow-up visits were performed at baseline, at 1 and 4 months after inclusion, while patients’ QoL was assessed by EQ-5D questionnaire. Results: 9 patients (1.6%) out of 563 enrolled CAD patients with >50% coronary stenosis, prematurely discontinued treatment. Mean heart rate decrease on study completion compared to baseline was -17.5 bpm (p<0.001), while mean number of angina attacks and nitroglycerin consumption decrease was -1.8 and -1.4 times/week respectively (p<0.001). The percentage of patients with angina CCS I (Canadian Cardiovascular Society classification), increased from 37% (baseline), to 87% (study completion) (p<0.001). For all dimensions of EQ-5D, the improvement was significant leading to an overall amelioration of daily functioning at study completion (p<0.001) At the 1st month of treatment, 52% of patients received 7.5 mg bid of Ivabradine, which was maintained throughout the study, while compliance to treatment was high; almost 97% of the population was taking their treatment “every day” or “quite often” throughout the study. Conclusions: Ivabradine administration presents a significant anti-anginal effect, while improving also QoL and restoring a level of satisfactory usual activity in patients with coronary stenosis >50% not submitted for revascularization.