Blood Pressure Regulation by the Carotid Sinus Nerve: Clinical Implications for Carotid Body Neuromodulation

Chronic carotid sinus nerve (CSN) electrical modulation through kilohertz frequency alternating current improves metabolic control in rat models of type 2 diabetes, underpinning the potential of bioelectronic modulation of the CSN as a therapeutic modality for metabolic diseases in humans. The CSN carries sensory information from the carotid bodies, peripheral chemoreceptor organs that respond to changes in blood biochemical modifications such as hypoxia, hypercapnia, acidosis, and hyperinsulinemia. In addition, the CSN also delivers information from carotid sinus baroreceptors—mechanoreceptor sensory neurons directly involved in the control of blood pressure—to the central nervous system. The interaction between these powerful reflex systems—chemoreflex and baroreflex—whose sensory receptors are in anatomical proximity, may be regarded as a drawback to the development of selective bioelectronic tools to modulate the CSN. Herein we aimed to disclose CSN influence on cardiovascular regulation, particularly under hypoxic conditions, and we tested the hypothesis that neuromodulation of the CSN, either by electrical stimuli or surgical means, does not significantly impact blood pressure. Experiments were performed in Wistar rats aged 10–12 weeks. No significant effects of acute hypoxia were observed in systolic or diastolic blood pressure or heart rate although there was a significant activation of the cardiac sympathetic nervous system. We conclude that chemoreceptor activation by hypoxia leads to an expected increase in sympathetic activity accompanied by compensatory regional mechanisms that assure blood flow to regional beds and maintenance of hemodynamic homeostasis. Upon surgical denervation or electrical block of the CSN, the increase in cardiac sympathetic nervous system activity in response to hypoxia was lost, and there were no significant changes in blood pressure in comparison to control animals. We conclude that the responses to hypoxia and vasomotor control short-term regulation of blood pressure are dissociated in terms of hypoxic response but integrated to generate an effector response to a given change in arterial pressure.

Effectiveness of radiofrequency renal denervation in diseases with increased sympathetic nervous system activity

The article discusses the role of sympathetic nervous system hyperactivity in the pathogenesis of various pathologies (hypertension, heart failure, atrial fibrillation, metabolic syndrome, diabetes and systemic inflammatory response syndrome). On the example of large randomized clinical trials using catheter-based radiofrequency ablation, the antihypertensive effect in patients with uncontrolled hypertension has been proven. The first experimental and clinical studies on the effectiveness of renal denervation in reducing the activity of inflammatory markers, the incidence of atrial fibrillation and ventricular arrhythmia episodes, and improving the left ventricular contractility. The first clinical results of the favorable effect of renal denervation on carbohydrate metabolism (insulin resistance and glycemic level) in patients with metabolic syndrome and diabetes have been studied in detail.

Laterality of Skin Temperature and Magnetic Resonance Imaging in Patients with Wallenberg Syndrome

Background: Recently, lateral differences in body surface temperature (BST) have been reported as a symptom of Wallenberg syndrome (WS), resulting from disturbances in the sympathetic nerve pathway. This study aimed to investigate the relationship between the laterality of BST and brain magnetic resonance imaging (MRI) findings in 12 patients with WS.Methods: BST was measured using an infrared thermal camera at 7±3 days and 90±30 days after symptom onset. The MRI findings were categorized as rostral, middle, and caudal medulla rostrocaudally and typical, ventral, large, dorsal, and lateral types in the horizontal direction.Results: MRI revealed medullary lesions on the right in five patients and on the left in seven patients. Two patients without lateralized BST had lateral caudal medullary infarction, and one patient had a dorsal middle medullary infarction. One patient with lateralized BST had a rostral medullary infarction and the other had a typical or large middle medulla infarction. Lateralized BST in patients with WS may disturb the sympathetic nervous system pathway that descends from the rostral ventrolateral medulla oblongata. Deficits in sweating and skin blood flow may cause BST laterality.Conclusion: This study showed that lateralized BST in patients with WS may be associated with disturbances in the sympathetic nervous pathway descending from the rostral ventrolateral medulla. These results support the assumption that autonomic dysfunction may be related to abnormal sensory symptoms in patients with WS.

Sodium-Glucose Cotransporter 2 Inhibitors Mechanisms of Action: A Review

Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i), or gliflozins, are a group of antidiabetic drugs that have shown improvement in renal and cardiovascular outcomes in patients with kidney disease, with and without diabetes. In this review, we will describe the different proposed mechanisms of action of SGLT2i. Gliflozins inhibit renal glucose reabsorption by blocking the SGLT2 cotransporters in the proximal tubules and causing glucosuria. This reduces glycemia and lowers HbA1c by ~1.0%. The accompanying sodium excretion reverts the tubuloglomerular feedback and reduces intraglomerular pressure, which is central to the nephroprotective effects of SGLT2i. The caloric loss reduces weight, increases insulin sensitivity, lipid metabolism, and likely reduces lipotoxicity. Metabolism shifts toward gluconeogenesis and ketogenesis, thought to be protective for the heart and kidneys. Additionally, there is evidence of a reduction in tubular cell glucotoxicity through reduced mitochondrial dysfunction and inflammation. SGLT2i likely reduce kidney hypoxia by reducing tubular energy and oxygen demand. SGLT2i improve blood pressure through a negative sodium and water balance and possibly by inhibiting the sympathetic nervous system. These changes contribute to the improvement of cardiovascular function and are thought to be central in the cardiovascular benefits of SGLT2i. Gliflozins also reduce hepcidin levels, improving erythropoiesis and anemia. Finally, other possible mechanisms include a reduction in inflammatory markers, fibrosis, podocyte injury, and other related mechanisms. SGLT2i have shown significant and highly consistent benefits in renal and cardiovascular protection. The complexity and interconnectedness of the primary and secondary mechanisms of action make them a most interesting and exciting pharmacologic group.

Spleen Perfusion as an Index of Gender Impact on Sympathetic Nervous System Response to Exercise

Objective: Sympathetic nervous system (SNS) reaction to exercise is gender dependent. Nevertheless, clinically applicable methods to identify this difference are still missing. An organ largely sensitive to SNS is the spleen whose response to exercise can be easily evaluated, being included in the field of view of myocardial perfusion imaging (MPI). Here, we aimed to verify whether gender interferes with the spleen perfusion and its response to exercise.Methods: For this purpose, we evaluated 286 original scans of consecutive patients submitted to MPI in the course of 2019. Our standard procedure implies a single-day stress-rest sequence with a gap of ≥2 h between the administrations of 180 and 500 MBq of 99mTc-Sestamibi, respectively. Imaging is performed 30 min after radiotracer administration, with scan duration set at 25 and 35 s per view, respectively. Non-gated scans were reconstructed with the filtered back-projection method. A volume of interest was drawn on the spleen and heart to estimate the dose-normalized average counting rate that was expressed in normalized counts per seconds (NCPS).Results: In all subjects submitted to exercise MPI (n = 228), NCPS were higher during stress than at rest (3.52 ± 2.03 vs. 2.78 ± 2.07, respectively; p < 0.01). This effect was not detected in the 58 patients submitted to dipyridamole-stress. The response to exercise selectively involved the spleen, since NCPS in heart were unchanged irrespective of the used stressor. This same response was dependent upon gender, indeed spleen NCPS during stress were significantly higher in the 75 women than in the 153 men (3.86 ± 1.8 vs. 3.23 ± 1.6, respectively, p < 0.01). Again, this variance was not reproduced by heart. Finally, spleen NCPS were lower in the 173 patients with myocardial reversible perfusion defects (summed difference score ≥3) than in the remaining 55, despite similar values of rate pressure product at tracer injection.Conclusion: Thus, exercise interference on spleen perfusion can be detected during MPI. This effect is dependent upon gender and ischemia confirming the high sensitivity of this organ to SNS activation.

Catecholamines are key modulators of ventricular repolarization patterns in the ball python (Python regius)

Ectothermic vertebrates experience daily changes in body temperature, and anecdotal observations suggest these changes affect ventricular repolarization such that the T-wave in the ECG changes polarity. Mammals, in contrast, can maintain stable body temperatures, and their ventricular repolarization is strongly modulated by changes in heart rate and by sympathetic nervous system activity. The aim of this study was to assess the role of body temperature, heart rate, and circulating catecholamines on local repolarization gradients in the ectothermic ball python (Python regius). We recorded body-surface electrocardiograms and performed open-chest high-resolution epicardial mapping while increasing body temperature in five pythons, in all of which there was a change in T-wave polarity. However, the vector of repolarization differed between individuals, and only a subset of leads revealed T-wave polarity change. RNA sequencing revealed regional differences related to adrenergic signaling. In one denervated and Ringer’s solution–perfused heart, heating and elevated heart rates did not induce change in T-wave polarity, whereas noradrenaline did. Accordingly, electrocardiograms in eight awake pythons receiving intra-arterial infusion of the β-adrenergic receptor agonists adrenaline and isoproterenol revealed T-wave inversion in most individuals. Conversely, blocking the β-adrenergic receptors using propranolol prevented T-wave change during heating. Our findings indicate that changes in ventricular repolarization in ball pythons are caused by increased tone of the sympathetic nervous system, not by changes in temperature. Therefore, ventricular repolarization in both pythons and mammals is modulated by evolutionary conserved mechanisms involving catecholaminergic stimulation.

Some psychophysiological parameters of a person during a passive orthostatic test

The study involved 14 volunteer students. Situational anxiety was determined, tests were carried out to determine simple and complex sensorimotor reactions, the cardiac rhythm of the subjects was recorded. Oxygen saturation was determined using an oximeter. Dynamic parameters were recorded: lying in a state of functional rest (background 1), vertical at 65-70° (vertical), lying after verticalization (horizontal), lying in a state of functional rest (background 2). The analysis of the data obtained was carried out using the Excel and StatPlus Pro programs. It was revealed that during verticalization, changes in the regulation of the heart activity of the subjects are carried out mainly due to the central mechanisms of regulation through the sympathetic nervous system. The transfer from a vertical to a horizontal state is accompanied by a restructuring of the regulatory system towards the activation of subcortical nerve centers and a shift in the balance of the SNS/PSNS towards the parasympathetic nervous system. Key words: passive orthostatic test, cardiac rhythm, simple sensorimotor reaction.