Medullary and Hypothalamic Functional Magnetic Imaging During Acute Hypoxia in Tracing Human Peripheral Chemoreflex Responses.

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Sleeping with Elevated Upper Body Does Not Attenuate Acute Mountain Sickness: Pragmatic Randomized Clinical Trial.

PURPOSE: Acute mountain sickness commonly occurs following ascent to high altitude and is aggravated following sleep. Cephalad fluid shifts have been implicated. We hypothesized that sleeping with the upper body elevated by 30º reduces the risk of acute mountain sickness. METHODS: In a pragmatic, randomized, observer-blinded field study at 4554 meters altitude, we investigated 134 adults aged 18-70 years with a Lake Louise score between 3 and 12 points on the evening of their arrival at the altitude. The individuals were exposed to sleeping on an inflatable cushion elevating the upper body by 30º or on a sham pillow in a horizontal position. The primary endpoint was the change in the Acute Mountain Sickness-Cerebral (AMS-C) score in the morning after sleeping at an altitude of 4554 meters compared with the evening before. Sleep efficiency was the secondary endpoint. RESULTS: Among 219 eligible mountaineers, 134 fulfilled the inclusion criteria and were randomized. The AMS-C score increased by 0.250 ± 0.575 in the control group and by 0.121 ± 0.679 in the intervention group (difference 0.105; 95% confidence interval, -0.098-0.308; P = .308). Oxygen saturation in the morning was 79% ± 6% in the intervention group and 78% ± 6% in the control group (P = .863). Sleep efficiency did not differ between groups (P = .115). CONCLUSIONS: Sleeping with the upper body elevated by 30° does not lead to relevant reductions in acute mountain sickness symptoms or hypoxemia at high altitude.

Efficacy of Electrical Baroreflex Activation Is Independent of Peripheral Chemoreceptor Modulation.

Arterial baroreflex activation through electrical carotid sinus stimulation has been developed for the treatment of resistant hypertension. Previous studies suggested that the peripheral chemoreflex is tonically active in hypertensive patients and may inhibit baroreflex responses. We hypothesized that peripheral chemoreflex activation attenuates baroreflex efficacy evoked by electrical carotid sinus stimulation. We screened 35 patients with an implanted electrical carotid sinus stimulator. Of those, 11 patients with consistent acute depressor response were selected (7 men/4 women, age: 67±8 years, body mass index: 31.6±5.2 kg/m2, 6±2 antihypertensive drug classes). We assessed responses to electrical baroreflex stimulation during normoxia, isocapnic hypoxia (SpO2: 79.0±1.5%), and hyperoxia (40% end-tidal O2 fraction) by measuring heart rate, blood pressure, ventilation, oxygen saturation, end-tidal CO2 and O2 fractions, and muscle sympathetic nerve activity. During normoxia, baroreflex activation reduced systolic blood pressure from 164±27 to 151±25 mm Hg (mean±SD, P<0.001), heart rate from 64±13 to 61±13 bpm (P=0.002), and muscle sympathetic nerve activity from 42±12 to 36±12 bursts/min (P=0.004). Hypoxia increased systolic blood pressure 8±12 mm Hg (P=0.057), heart rate 10±6 bpm (P<0.001), muscle sympathetic nerve activity 7±7 bursts/min (P=0.031), and ventilation 10±7 L/min (P=0.002). However, responses to electrical carotid sinus stimulation did not differ between hypoxic and hyperoxic conditions: systolic blood pressure: -15±7 versus -14±8 mm Hg (P=0.938), heart rate: -2±3 versus -2±2 bpm (P=0.701), and muscle sympathetic nerve activity: -6±4 versus -4±3 bursts/min (P=0.531). We conclude that moderate peripheral chemoreflex activation does not attenuate acute responses to electrical baroreflex activation therapy in patients with resistant hypertension. These patients provided insight into human baroreflex-chemoreflex interactions that could not be gained otherwise.

Electrical carotid sinus stimulation in treatment resistant arterial hypertension.

Treatment resistant arterial hypertension is commonly defined as blood pressure that remains above goal in spite of the concurrent use of three antihypertensive agents of different classes. The sympathetic nervous system promotes arterial hypertension and cardiovascular as well as renal damage, thus, providing a logical treatment target in these patients. Recent physiological studies suggest that baroreflex mechanisms contribute to long-term control of sympathetic activity and blood pressure providing an impetus for the development of electrical carotid sinus stimulators. The concept behind electrical stimulation of baroreceptors or baroreflex afferent nerves is that the stimulus is sensed by the brain as blood pressure increase. Then, baroreflex efferent structures are adjusted to counteract the perceived blood pressure increase. Electrical stimulators directly activating afferent baroreflex nerves were developed years earlier but failed for technical reasons. Recently, a novel implantable device was developed that produces an electrical field stimulation of the carotid sinus wall. Carefully conducted experiments in dogs provided important insight in mechanisms mediating the depressor response to electrical carotid sinus stimulation. Moreover, these studies showed that the treatment success may depend on the underlying pathophysiology of the hypertension. Clinical studies suggest that electrical carotid sinus stimulation attenuates sympathetic activation of vasculature, heart, and kidney while augmenting cardiac vagal regulation, thus lowering blood pressure. Yet, not all patients respond to treatment. Additional clinical trials are required. Patients equipped with an electrical carotid sinus stimulator provide a unique opportunity gaining insight in human baroreflex physiology.

Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients.

In animals, electric field stimulation of carotid baroreceptors elicits a depressor response through sympathetic inhibition. We tested the hypothesis that the stimulation acutely reduces sympathetic vasomotor tone and blood pressure in patients with drug treatment-resistant arterial hypertension. Furthermore, we tested whether the stimulation impairs the physiological baroreflex regulation. We studied 7 men and 5 women (ages 43 to 69 years) with treatment-resistant arterial hypertension. A bilateral electric baroreflex stimulator at the level of the carotid sinus (Rheos) was implanted > or =1 month before the study. We measured intra-arterial blood pressure, heart rate, muscle sympathetic nerve activity (microneurography), cardiac baroreflex sensitivity (cross-spectral analysis and sequence method), sympathetic baroreflex sensitivity (threshold technique), plasma renin, and norepinephrine concentrations. Measurements were performed under resting conditions, with and without electric baroreflex stimulation, for > or =6 minutes during the same experiment. Intra-arterial blood pressure was 193+/-9/94+/-5 mm Hg on medications. Acute electric baroreflex stimulation decreased systolic blood pressure by 32+/-10 mm Hg (range: +7 to -108 mm Hg; P=0.01). The depressor response was correlated with a muscle sympathetic nerve activity reduction (r(2)=0.42; P<0.05). In responders, muscle sympathetic nerve activity decreased sharply when electric stimulation started. Then, muscle sympathetic nerve activity increased but remained below the baseline level throughout the stimulation period. Heart rate decreased 4.5+/-1.5 bpm with stimulation (P<0.05). Plasma renin concentration decreased 20+/-8% (P<0.05). Electric field stimulation of carotid sinus baroreflex afferents acutely decreased arterial blood pressure in hypertensive patients, without negative effects on physiological baroreflex regulation. The depressor response was mediated through sympathetic inhibition.

Influence of St John's wort on catecholamine turnover and cardiovascular regulation in humans.

BACKGROUND: St John's wort (Hypericum perforatum) is a popular over-the-counter antidepressant. Its antidepressive effect has been attributed in part to inhibition of monoamine transporters and monoamine oxidase, on the basis of in vitro studies. METHODS: In a double-blind, randomized, placebo-controlled, crossover study, 16 healthy subjects (11 men and 5 women; mean age, 31 +/- 5 years) ingested either St John's wort (300 mg three times daily) or placebo for 7 days. Imipramine treatment (50 mg three times daily) in 7 subjects served as a positive control. After treatment, physiologic and biochemical tests included cardiovascular reflex testing, graded head-up tilt testing, and plasma catecholamine determinations. RESULTS: St John's wort had no effect on blood pressure, heart rate, heart rate variability, or blood pressure variability, regardless of the test condition. St John's wort had no effect on plasma concentrations of norepinephrine and its main metabolite, dihydroxyphenylglycol, whereas plasma dihydroxyphenylacetic acid (DOPAC; the main metabolite of dopamine) concentrations increased in every subject (1661 +/- 924 pg/mL versus 1110 +/- 322 pg/mL with placebo, P=.04). In contrast, imipramine increased resting blood pressure (124 +/- 10 mmHg/71 +/- 5 mmHg versus 110 +/- 8 mmHg/61 +/- 6 mmHg with placebo, P=.005 for systolic values and P=.003 for diastolic values) and heart rate (74 +/- 7 beats/min versus 62 +/- 6 beats/min with placebo, P=.005) and elicited a marked orthostatic tachycardia (increase in heart rate of 43 +/- 17 beats/min versus 26 +/- 8 beats/min with placebo, P=.006). CONCLUSIONS: Our findings challenge the concept that St John's wort elicits a major change in norepinephrine uptake or monoamine oxidase activity in vivo. The consistent increase in plasma DOPAC concentrations might suggest a novel mode of action or an inhibitory effect on dopamine beta-hydroxylase that should be followed up. We propose that a combination of physiologic and biochemical profiling may help better define the mode of action and potential side effects of herbal remedies.