Altered Cardiovascular Reactivity to and Recovery from Cold Face Test-Induced Parasympathetic Stimulation in Essential Hypertension

Essential hypertension is associated with increased sympathetic and diminished parasympathetic activity as well as impaired reactivity to sympathetic stimulation. However, reactivity and recovery from parasympathetic stimulation in hypertension are unknown. We investigated reactivity and recovery to primarily parasympathetic stimulation by Cold Face Test (CFT) in essential hypertension. Moreover, we tested whether chronic stress modulates CFT-reactivity dependent on hypertension status. The CFT was conducted by applying a cold face-mask for 2 min in 24 unmedicated, otherwise healthy hypertensive men and in 24 normotensive controls. Systolic and diastolic blood pressure (BP) and heart rate (HR) were measured repeatedly. Chronic stress was assessed with the Trier-Inventory-for-Chronic-Stress-Screening-Scale. Hypertensives did not exhibit diastolic BP decreases after CFT-cessation (p = 0.59) as did normotensives (p = 0.002) and failed to show HR decreases in immediate response to CFT (p = 0.62) when compared to normotensives (p < 0.001). Systolic BP reactivity and recovery patterns did not differ between hypertensives and normotensives (p = 0.44). Chronic stress moderated HR (p = 0.045) but not BP CFT-reactivity (p′s > 0.64) with chronically stressed normotensives showing similar HR reactivity as hypertensives. Our findings indicate impaired diastolic BP and HR reactivity to and recovery from CFT in hypertensives and a moderating effect of chronic stress on HR reactivity potentially reflecting reduced relaxation ability of the cardiovascular system.

Cardiac Autonomic Dysfunction and Risk of Sudden Unexpected Death in Epilepsy

Objective:We aimed to test whether patients who died from sudden unexpected death in epilepsy (SUDEP) had an abnormal cardiac autonomic response to sympathetic stimulation by hyperventilation.Methods:We conducted a retrospective, observational, case-control study of a group of patients who died from SUDEP and controls who were matched with the patients for epilepsy type, drug resistance, sex, age at electroencephalogram recording, age at onset of epilepsy, and duration of epilepsy. We analyzed the heart rate (HR) and heart rate variability (HRV) at rest, during and after hyperventilation performed during the patient’s last electroencephalogram recording before SUDEP. In each group, changes over time in HRV indexes were analyzed using linear mixed models.Results:Twenty patients were included in each group. In the control group, the HR increased and the RMSSD decreased during the hyperventilation and then returned to the baseline values. In the SUDEP group, however, the HR and RMSSD did not change significantly during or after hyperventilation. A difference in HR between the end of the hyperventilation and 4 min after its end discriminated well between SUDEP patients and control patients (AUC: 0.870; sensitivity: 85%; specificity: 75%).Conclusion:Most of patients with subsequent SUDEP have an abnormal cardiac autonomic response to sympathetic stimulation through hyperventilation. An index reflecting the change in heart rate upon hyperventilation (dHRh) might be predictive of the risk of SUDEP and could be used to select patients at risk of SUDEP for inclusion in trials assessing protective measures.

Sympathetic stimulation increases serum lactate concentrations in patients admitted with sepsis: implications for resuscitation strategies

Background Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis. Methods Retrospective analysis of prospectively collected clinical data from four community-based hospitals and one academic medical center. 8173 adults were included. Heart rate (HR) was used as a surrogate marker of sympathetic stimulation. HR, MAP, and lactate levels were measured upon presentation. Results MAP and HR interacted to affect lactate levels with the highest levels observed in patients with low MAP and high HR (3.6 mmol/L) and the lowest in patients with high MAP and low HR (2.2 mmol/L). The overall mortality rate was 12.4%. Each 10 beats/min increase in HR increased the odds of death 6.0% (95% CI 2.6% to 9.4%), each 1 mmol/L increase in lactate increased the odds of death 20.8% (95% CI 17.4% to 24.2%), whereas each 10 mmHg increase in MAP reduced the odds of death 12.3% (95% CI 9.2% to 15.4%). However, HR did not moderate or mediate the association between lactate and death. Conclusions In septic patients, lactate production was associated with increased sympathetic activity (HR ≥ 90) and hypotension (MAP < 65 mmHg) and was a significant predictor of mortality. Because HR, lactate, and MAP were associated with mortality, our data support the present strategy of using these measurements to gauge severity of illness upon presentation. Since HR did not moderate or mediate the association between lactate and death, criticisms alleging that lactate caused by sympathetic stimulation is adaptive (i.e., less harmful) do not appear substantiated.

Immediate effect of interscapular cupping on blood pressure, oxygen saturation, pulse rate and chest expansion in sedentary smoker students

Objectives Increased sympathetic stimulation in smokers may be a risk factor for pulmonary and cardiovascular diseases. This study was conducted to assess the immediate effect of interscapular cupping on blood pressure (BP), oxygen (O2) saturation, chest expansion (CE), pulse rate (PR) in sedentary male smoker students. Methods Forty sedentary male smoker students– aged 18–25 years -were divided randomly into two equal numbered groups; wet cupping (WC) and dry cupping (DC) groups. Systolic and diastolic BP, upper and lower CE, O2 saturation and PR were measured immediately before and after a single cupping session in both groups. Results Both WC and DC types showed improvements in all measurements with a high statistically significant difference (p<0.05). Conclusions Interscapular cupping enhanced CE, O2 saturation, BP and PR in sedentary male smoker students.

Thyroid hormones in the regulation of brown adipose tissue thermogenesis

A normal thyroid status is crucial for body temperature homeostasis, as thyroid hormone regulates both heat loss and conservation as well as heat production in thermogenic tissues. Brown adipose tissue (BAT) is the major site of non-shivering thermogenesis and an important target of thyroid hormone action. Thyroid hormone not only regulates the tissue’s sensitivity to sympathetic stimulation by norepinephrine, but also the expression of uncoupling protein 1, the key driver of BAT thermogenesis. Vice versa, sympathetic stimulation of BAT triggers the expression of deiodinase type II, an enzyme that enhances local thyroid hormone availability and signaling. This review summarizes the current knowledge on how thyroid hormone controls BAT thermogenesis, aiming to dissect the direct actions of the hormone in BAT and its indirect actions via the central nervous system, browning of white adipose tissue or heat loss over body surfaces. Of particular relevance is the apparent dose dependency of the observed effects, as we find that minor or moderate changes in thyroid hormone levels often have different effects as compared to high pharmacological doses. Moreover, we conclude that the more recent findings require a reevaluation of older studies, as key aspects such as heat loss or central BAT activation may not have received the necessary attention during the interpretation of these early findings. Finally, we provide a list of what we believe are the most relevant questions in the field that to date are still enigmatic and require further studies.

Beta-Adrenergic Receptor Stimulation Limits the Cellular Proarrhythmic Effects of Chloroquine and Azithromycin

Background: The antimalarial drug chloroquine and antimicrobial drug azithromycin have received significant attention during the current COVID-19 pandemic. Both drugs can alter cardiac electrophysiology and have been associated with drug-induced arrhythmias. Meanwhile, sympathetic activation is commonly observed during systemic inflammation and oxidative stress (e.g., in SARS-CoV-2 infection), and may influence the electrophysiological effects of chloroquine and azithromycin. Here, we investigated the effect of beta-adrenergic stimulation on proarrhythmic properties of chloroquine and azithromycin using a detailed in silico model of ventricular electrophysiology. Methods: Concentration-dependent chloroquine and azithromycin-induced alterations in ion-channel function were incorporated into the Heijman canine ventricular cardiomyocyte model. Single and combined drug effects on action-potential (AP) properties were analyzed using a population of 592 models accommodating inter-individual variability. Sympathetic stimulation was simulated by an increase in pacing rate and experimentally validated isoproterenol-induced changes in ion-channel function. Results: At 1 Hz pacing, therapeutic doses of chloroquine and azithromycin (5 and 20 &micro;M, respectively) individually prolonged AP duration (APD) by 33% and 13%. Their combination produced synergistic APD prolongation (+161%) with incidence of proarrhythmic early afterdepolarizations in 53.5% of models. Increasing the pacing frequency to 2 Hz shortened APD and together with 1 &micro;M isoproterenol corrected the drug-induced APD prolongation. No afterdepolarizations occurred following increased rate and simulated application of 0.1-1 &micro;M isoproterenol. Conclusion: Sympathetic stimulation limits chloroquine- and azithromycin-induced proarrhythmia by reducing their APD-prolonging effect, suggesting the importance of heart rate and autonomic status monitoring in particular conditions (e.g., COVID-19).