Supportive treatment of vascular dysfunction in pediatric subjects with obesity: the OBELIX study

Introduction Overweight or obese children develop abnormal endothelial cell dysfunction and arterial intima–media thickening with increased vasomotor tone and inflammation. Curcumin, resveratrol, zinc, magnesium, selenium, and vitamin D have shown beneficial effects on endothelial function. We test, among overweight and obese pediatric subjects, the effects on the endothelium of a combination of curcumin, resveratrol, zinc, magnesium, selenium, and vitamin D. Methods Forty-eight subjects (6–17 years) were randomized into two groups (placebo vs treatment) attended three visits at 0, 3, and 6 months (±15 days). Endothelial function was assessed by means of a post-occlusive release hyperemic (PORH) test for estimation of delta flow (DF) and hyperemic AUC index, and a heat provocation test (HPT) to measure DF HPT (DFHPT). Results Significant DF difference was noted at 6 months in both groups (p < 0.001). Overall time trend was significantly different between baseline, 3 months, and 6 months both in placebo (p < 0.05) and treatment (p < 0.001) groups and their comparison (p < 0.001). No differences were noted in hyperemic AUC index (3 and 6 months), whilst there were significant differences in time trends of rreatment (p < 0.001) and placebo (p < 0.05) groups and their comparison (p < 0.001). DFHPT difference between groups was significant at 3 and 6 months (p < 0.05). The overall time trend was significant exclusively in Treatment group between 3 and 6 months (p < 0.05). Correlation with anthropometrics was found for DF and body mass index (r = 0.677 6 months, p < 0.05), as well as for hyperemic AUC index and males (r = 0.348, p < 0.05), while DFHPT showed no correlation. Conclusion Curcumin, resveratrol, zinc, magnesium, selenium, and vitamin D appear to be promising in enhancing endothelial function by improvement of both DF in the PORH test and DF in the HPT, lowering the risk of developing cardiovascular diseases in overweight and obese pediatric subjects.

Implications of Endothelial Cell-Mediated Dysfunctions in Vasomotor Tone Regulation

Cardiovascular diseases (CVD) constitute the major cause of death worldwide and show a higher prevalence in the adult population. The human umbilical cord consistsof two arteries and one vein, both composed of three tunics. The tunica intima, lined with endothelial cells, regulates vascular tone through the production/release of vasoregulatory substances. These substances can be vasoactive factors released by endothelial cells (ECs) that cause vasodilation (NO, PGI2, EDHF, and Bradykinin) or vasoconstriction (ET1, TXA2, and Ang II) depending on the cell type (ECs or SMC) that reacts to the stimulus. Vascular studies using ECs are important for the analysis of cardiovascular diseases since endothelial dysfunction is an important CVD risk factor. In this paper, we will address the morphological characteristics of the human umbilical cord and its component vessels. the constitution of the vascular endothelium, and the evolution of human umbilical cord-derived endothelial cells when isolated. Moreover, the role played by the endothelium in the vasomotor tone regulation, and how it may be associated with the existence of CVD, were discussed.

Low ventilatory responsiveness to transient hypoxia or breath-holding predicts fast marathon performance in healthy middle-aged and older men

The aim of this study was to test the utility of haemodynamic and autonomic variables (e.g. peripheral chemoreflex sensitivity [PCheS], blood pressure variability [BPV]) for the prediction of individual performance (marathon time and VO2max) in older men. The post-competition vasodilation and sympathetic vasomotor tone predict the marathon performance in younger men, but their prognostic relevance in older men remains unknown. The peripheral chemoreflex restrains exercise-induced vasodilation via sympathetically-mediated mechanism, what makes it a plausible candidate for the individual performance marker. 23 men aged ≥ 50 year competing in the Wroclaw Marathon underwent an evaluation of: resting haemodynamic parameters, PCheS with two methods: transient hypoxia and breath-holding test (BHT), cardiac barosensitivity, heart rate variability (HRV) and BPV, plasma renin and aldosterone, VO2max in a cardiopulmonary exercise test (CPET). All tests were conducted twice: before and after the race, except for transient hypoxia and CPET which were performed once, before the race. Fast marathon performance and high VO2max were correlated with: low ventilatory responsiveness to hypoxia (r = − 0.53, r = 0.67, respectively) and pre-race BHT (r = − 0.47, r = 0.51, respectively), (1) greater SD of beat-to-beat SBP (all p < 0.05). Fast performance was related with an enhanced pre-race vascular response to BHT (r = − 0.59, p = 0.005). The variables found by other studies to predict the marathon performance in younger men: post-competition vasodilation, sympathetic vasomotor tone (LF-BPV) and HRV were not associated with the individual performance in our population. The results suggest that PCheS (ventilatory response) predicts individual performance (marathon time and VO2max) in men aged ≥ 50 yeat. Although cause-effect relationship including the role of peripheral chemoreceptors in restraining the post-competition vasodilation via the sympathetic vasoconstrictor outflow may be hypothesized to underline these findings, the lack of correlation between individual performance and both, the post-competition vasodilation and the sympathetic vasomotor tone argues against such explanation. Vascular responsiveness to breath-holding appears to be of certain value for predicting individual performance in this population, however.

Unusual Cases of Syncope in the Pediatric Age Group

Syncope is common in the pediatric population and occurs in up to 15 percent of children prior to the end of adolescence. While the etiology of syncope in children is often benign and the majority of cases can be explained by isolated changes in vasomotor tone, a thorough evaluation is warranted to rule out more serious, life-threatening causes of syncope. Here, we present three atypical cases of syncope: a young judo player with recurrent syncope and dizziness, a teenage boy with syncopal episodes always preceded by stretching, and a child who experienced urticaria before losing consciousness. Herein, we review the pathophysiology, diagnosis, and management of syncope in children and adolescents.

Deletion of Orphan G Protein-Coupled Receptor GPR37L1 in Mice Alters Cardiovascular Homeostasis in a Sex-Specific Manner

GPR37L1 is a family A orphan G protein-coupled receptor (GPCR) with a putative role in blood pressure regulation and cardioprotection. In mice, genetic ablation of Gpr37l1 causes sex-dependent effects; female mice lacking Gpr37l1 (GPR37L1−/−) have a modest but significant elevation in blood pressure, while male GPR37L1−/− mice are more susceptible to cardiovascular dysfunction following angiotensin II-induced hypertension. Given that this receptor is highly expressed in the brain, we hypothesize that the cardiovascular phenotype of GPR37L1−/− mice is due to changes in autonomic regulation of blood pressure and heart rate. To investigate this, radiotelemetry was employed to characterize baseline cardiovascular variables in GPR37L1−/− mice of both sexes compared to wildtype controls, followed by power spectral analysis to quantify short-term fluctuations in blood pressure and heart rate attributable to alterations in autonomic homeostatic mechanisms. Additionally, pharmacological ganglionic blockade was performed to determine vasomotor tone, and environmental stress tests were used to assess whether cardiovascular reactivity was altered in GPR37L1−/− mice. We observed that mean arterial pressure was significantly lower in female GPR37L1−/− mice compared to wildtype counterparts, but was unchanged in male GPR37L1−/− mice. GPR37L1−/− genotype had a statistically significant positive chronotropic effect on heart rate across both sexes when analyzed by two-way ANOVA. Power spectral analysis of these data revealed a reduction in power in the heart rate spectrum between 0.5 and 3 Hz in female GPR37L1−/− mice during the diurnal active period, which indicates that GPR37L1−/− mice may have impaired cardiac vagal drive. GPR37L1−/− mice of both sexes also exhibited attenuated depressor responses to ganglionic blockade with pentolinium, indicating that GPR37L1 is involved in maintaining sympathetic vasomotor tone. Interestingly, when these mice were subjected to aversive and appetitive behavioral stressors, the female GPR37L1−/− mice exhibited an attenuation of cardiovascular reactivity to aversive, but not appetitive, environmental stimuli. Together, these results suggest that loss of GPR37L1 affects autonomic maintenance of blood pressure, giving rise to sex-specific cardiovascular changes in GPR37L1−/− mice.

Postoperative Stroke in Patients After Spinal Anesthesia and Disparate Response Patterns of Carotid or Cerebral Blood Flow and Baroreflex Functionality to Spinal Bupivacaine in Rats

Spinal anesthesia is generally accepted as an effective and safe practice. Three rare incidents of postoperative cerebral infarction after surgery under spinal anesthesia with bupivacaine prompted us to assess whether spinal bupivacaine may impact carotid or cerebral blood flow and baroreflex functionality. We found that all three patients shared common pathology of stenosis or atheromatous lesions in the carotid or middle cerebral artery. In a companion animal study, we further observed that subarachnoid application of bupivacaine that reached low thoracic spinal cord in male Sprague‐Dawley rats elicited an initial (Phase I) reduction in mean arterial pressure (MAP), carotid blood flow (CBF) and baroreflexmediated sympathetic vasomotor tone, all of which returned to baseline in Phase II. Whereas heart rate (HR) exhibited sustained reduction, cardiac vagal baroreflex, baroreflex efficiency index (BEI) and tissue perfusion and oxygen in cerebral cortex supplied by middle cerebral artery remained unaltered during both phases. However, in one‐third of animals studied, Phase II gave way to a Phase III characterized by secondary hypotension and depressed baroreflex‐mediated sympathetic vasomotor tone, along with continuous decline in HR, sustained cardiac vagal baroreflex, decreased BEI, and reduction in CBF and tissue perfusion or oxygen in cerebral cortex. We conclude that carotid and cerebral blood flow can be compromised after spinal anesthesia, and impaired baroreflex‐mediated sympathetic vasomotor tone that leads to hypotension plays a contributory role.

Assessment of serum nitric oxide level in cigarette smoking

Background: Cigarette smoke has been implicated as a major risk factor in various diseases associated with endothelial dysfunction like essential hypertension, atherosclerosis and related cardiovascular dysfunction. Nitric oxide, an important second messanger plays a pivotal role in maintaining vasomotor tone and its level is also found to be altered in many chronic vascular disorders. The particulates in cigarette smoke is presumed to affect the production NO in vascular endothelium. Hence, it is proposed to study the effect of cigarette smoking in influencing Nitric oxide level. The study sample comprised of 138 chronic smokers and144 apparently healthy nonsmokers . Plasma glucose, total cholesterol (TC), high density lipoprotein cholesterol (HDL-c) and triglyceride concentration (TGL) were determined enzymatically and serum NO index (NOx) estimated by Griess method. It was found that serum NOx level was not influenced by biochemical parameters like plasma glucose and lipid profile. The estimated mean NOx levels was slightly lower in smokers(15.92 with SD 5.4) than in nonsmokers (16.66with SD 6.73) . However the difference was not statistically significant ( P= 0.31). It is concluded that there is no significant correlation between serum nitric oxide level and smoking, based on this study.

Causal contribution of malignancy to anomalous baroreflex functionality in patients with cancer: An overlooked aspect of cardio-oncology

The current trend in cardio-oncology places major emphasis on circulatory toxicity induced by cancer therapy. Whether malignancy itself is a direct contributing factor to cardiovascular dysfunctions and baroreflex dysregulation in patients with cancer, however, has rarely appeared in literature. The present study addressed this largely overlooked aspect of cardio-oncology by evaluating blood pressure, heart rate and baroreflex functionality before and after curative surgery in patients with oral cavity squamous cell carcinoma (OSCC). We found that these patients exhibited reduced baroreflex-mediated sympathetic vasomotor tone and augmented cardiac vagal baroreflex, and such inherent anomalies were readily reversed to levels of healthy controls after surgical removal of the primary tumor. It is concluded that by being more prone to hypotension and bradycardia, anomalous baroreflex functionality causally induced by malignancy predisposes patients with cancer to detrimental cardiovascular abnormalities that may be further exacerbated by cancer therapy.