[Recent progresses in the treatment of dyslipidemia]. / Actualités thérapeutiques en lipidologie.

There is a linear relationship between LDLcholesterol plasma concentration and coronary events, both in patients with stable angina pectoris and after an acute event. All medications that affect the lipid profile do not have a favorable effect on cardiovascular events (i.e. niacin, inhibitors of the cholesteryl ester transfer protein). Statins increase slightly the risk of type II diabetes in subjects at risk. We have also learnt that statins activate a transcription factor that increases LDL-cholesterol receptors, as well as a protein named " PCSK9 ". This latter protein reduces the number of LDL-cholesterol receptors on the hepatocyte and hampers thereby the LDLcholesterol lowering effects of statins. Spontaneous mutations that render PCSK9 ineffective reduce the LDL-cholesterol, and prevent coronary heart disease. Similar observations have been reproduced with numerous mutations that affect LDL-cholesterol levels. If a monoclonal antibody against PSCK9 is provided in addition to statin therapy, LDLcholesterol plasma concentration falls at unprecedented low concentrations of 30 mg/dl. 4.4% of these patients present a myocardial infarction, as compared to 6.3% in the placebo group. This new class of medication seems therefore promising for the secondary prevention in patients at risk of recurrent ischemic events.

Il y a une relation linéaire entre la concentration de LDL-cholestérol plasmatique et la survenue d'événements coronaires, tant après un événement coronaire aigu que dans la pathologie coronaire stable. Tous les agents pharmacologiques qui modifient le profil lipidique n'ont toutefois pas un effet positif sur les évènements cardiovasculaires (par exemple la niacine, les inhibiteurs de la " cholesteryl ester transfer protein "). Les statines augmentent discrètement le risque de diabète de type II chez des patients prédisposés. On sait aussi à présent que les statines accroissent l'expression d'un facteur de transcription qui augmente à la fois les récepteurs au LDL-cholestérol et une protéine dénommée " PCSK9 ". PCSK9 réduit le nombre de récepteurs au LDL-cholestérol sur l'hépatocyte, et limite par conséquent l'efficacité des statines. Les mutations qui rendent PCSK9 inopérant réduisent le LDL-cholestérol ainsi que le risque coronarien. Ceci a été reproduit avec un grand nombre de mutations qui affectent les concentrations du LDL-cholestérol plasmatique. Si on ajoute à une statine des anticorps monoclonaux qui inactivent PCSK9, le LDL cholestérol diminue considérablement à 30 mg/dl et seul 4,4 % des patients présentent un infarctus myocardique, contre 6,3 % dans le groupe placébo. Ces médicaments constituent par conséquent une nouvelle classe thérapeutique prometteuse pour la prévention secondaire d'évènements ischémiques chez des patients à risque.

[Hypertension and cardiovascular prevention: what has changed in 2014]. / Hypertension artérielle et prévention cardiovasculaire: ce qui a changé en 2014.

During the two past years, several recommendations regarding the management of the hypertensive patient and cardiovascular risk have been published. This article is focused on the main changes which are important for the general practitioner.

[Atrial fibrillation: recent progress]. / Fibrillation auriculaire: progrès récents.

Atrial fibrillation is the most common cardiac arrhythmia. Pharmacological treatment plays still an important role in the management of this disease. However, pulmonary vein isolation techniques are more and more important due to the high rate of recurrences and many side effects associated with antiarrhythmic drugs. This article is focused on the main changes that are important for the general practitioner in his daily clinical practice.

[Renal denervation: new treatment for refractory hypertension?]. / Dénervation rénale: nouveau traitement de l'hypertension artérielle résistante?

Sympathetic renal hyperactivity is involved hypertension and in its progression towards organ damages. Using femoral access, a dedicated ablation catheter can be inserted into the renal vessels to deliver high frequency energy in the arterial wall. This therapy leads to a focal heating, which ablates the renal nerve fibers running in the adventitia. First clinical results (Simplicity HTN 1 and HTN 2 trials) have demonstrated a significant and sustained decrease in office blood pressure. The response rate to this therapy was about 85 to 90%. This procedure did not cause serious adverse event and seems to have also positive impact on glucose metabolism and exercise capacity. Based on these first results, renal denervation appears as a new interesting therapy, which requires further studies to better define its place in the antihypertensive therapeutic arsenal. Actually, it should not be considered as an alternative to pharmacological therapy and renal denervation should be only proposed to patients with resistant hypertension. Prior to renal denervation, an upstream work has to be done to ensure an adequate patient selection. The mandatory point is to ensure that patient scheduled for this therapy respond to the definition of arterial resistant hypertension. Because of the narrowed limit between the very common situation of "uncontrolled" hypertension and the "true resistant" group, we proposed a 3 steps algorithm that can help for patient selection.

Effects of ß2-adrenergic stimulation on exercise capacity in normal subjects.

ß2-Adrenergic receptor agonists are believed to present with ergogenic properties. However, how combined respiratory, cardiovascular and muscular effects of these drugs might affect exercise capacity remain incompletely understood. The effects of salbutamol were investigated in 23 healthy subjects. The study was randomised, placebo-controlled in double-blind and followed a cross-over design. Salbutamol was given at the dose of 10 µg/min in 11 subjects and 20 µg/min iv in the other 12 subjects. Measurements included muscle sympathetic nerve activity (MSNA), ventilatory responses to hyperoxic hypercapnia (7% CO(2) in O(2,) central chemoreflex), isocapnic hypoxia (10% O(2) in N(2), peripheral chemoreflex) and isometric muscle contraction followed by a local circulatory arrest (metaboreflex), cardiopulmonary exercise test (CPET) variables and isokinetic muscle strength. Salbutamol 10 µg/min increased heart rate and blood pressure, while MSNA burst frequency remained unchanged. Peripheral chemosensitivity increased, as evidenced by an increased ventilatory response to hypoxia, but ventilatory responses to hypercapnia or muscle ischaemia remained unchanged. The effects of salbutamol 20 µg/min were similar. Both doses of salbutamol did not affect CPET. Only the higher dose of salbutamol decreased the anaerobic threshold, but this was not associated with a change in VO(2) max. Salbutamol increased the slopes of ventilation as a function of VO(2) (P < 0.05) and VCO(2) (P < 0.001) during CPET. Maximal isokinetic muscle strength was not affected by salbutamol. In conclusion, the acute administration of either low or high dose salbutamol does not affect exercise capacity in normal subjects, in spite of an earlier anaerobic threshold and increased chemosensitivity.

Altered interaction between cardiac vagal influence and delta sleep EEG suggests an altered neuroplasticity in patients suffering from major depressive disorder.

OBJECTIVE: Major depressive disorder (MDD), which is associated with altered neuroplasticity and increased relative cardiac sympathic activity, enhances the risk of cardiovascular pathologies. Interaction between cardiac sympatho-vagal indexes and delta sleep power is probably altered in MDD. METHOD: Sleep characteristics and cardiac sympatho-vagal indexes of 10 depressive patients were compared to 10 control men across the first three non-rapid eye movement (NREM)-REM cycles. Interaction between normalized high frequency (HF) and delta power bands was studied using coherence analysis. RESULTS: Patients showed increased sleep latency, stage 1 and wake durations. No differences in heart rate variabilities were observed: Total power, HF and RR-interval decreased from NREM to REM sleep and wakefulness in both groups. Gain value was lower in patients while coherence and phase shift were similar between groups. Modifications in HF appear 8 min before modifications in delta. CONCLUSION: Major depressive disorder is related to an altered link between cardiac vagal influence and delta sleep, suggesting disorders in cardiovascular controls and an altered neuroplasticity.

Digoxin increases peripheral chemosensitivity and the ventilatory response to exercise in normal subjects.

1. The contribution of peripheral chemoreceptors to the regulation of ventilation during exercise remains incompletely understood. Digoxin has been reported to increase chemoreflex sensitivity in humans. In the present randomized, cross-over, double-blind study, we tested the hypothesis that this increases the ventilatory response to exercise in normal subjects, as assessed by changes in minute ventilation (V(E)) in response to the rate of CO(2) production (VCO(2)). 2. Minute ventilation, end-tidal PCO(2), pulse oximetric O(2) saturation (S(p)O(2)), heart rate and blood pressure (BP) were measured in 11 healthy young male untrained subjects after intravenous infusion of digoxin (0.01 mg/kg) or placebo during normoxia, isocapnic hypoxia and hyperoxic hypercapnoea. All participants underwent a maximum cardiopulmonary exercise test. 3. During normoxia, digoxin increased systolic BP only. During hypoxia, digoxin increased V(E) compared with placebo (P = 0.009) for the same fall in S(p)O(2) (P = NS). Moreover, no significant effects on ventilation and haemodynamic responses were recorded during hypercapnoea. Digoxin increased the V(E) /VCO(2) slope above the anaerobic threshold from 30.4 +/- 2.9 to 32.8 +/- 3.7 (P < 0.05), but did not affect VO(2max). 4. In conclusion, enhanced peripheral chemosensitivity with digoxin increases the ventilatory response to CO(2) production above the anaerobic threshold, but does not affect exercise capacity in healthy humans.

Acute effect of sidestream cigarette smoke extract on vascular endothelial function.

Acute exposure to passive smoking adversely affects vascular function by promoting oxidative stress and endothelial dysfunction. However, it is not known whether tobacco sidestream (SS) smoke has a greater deleterious effect on the endothelium than non-tobacco SS smoke and whether these effects are related to nicotinic endothelial stimulation. To test these hypotheses, endothelial-dependent relaxation and superoxide anion production were assessed in isolated rat aortas incubated with tobacco SS smoke, non-tobacco SS smoke, or pure nicotine. Tobacco SS smoke decreased the maximal relaxation to acetylcholine (Ach) from 79 +/- 6% to 57 +/- 7.3% (% inhibition of phenylephrine-induced plateau, P < 0.001) and increased superoxide anion production from 31 +/- 9.7 to 116 +/- 24 count/10 sec/mg (P < 0.01, lucigenin-enhanced chemiluminescence technique). The non-tobacco SS smoke extract had no significant effect on the response to Ach but increased superoxide anion production in the aortic wall to 133 +/- 2 count/10 sec/mg (P < 0.001). Furthermore, concentration-response curves to Ach and superoxide production remained unaltered with nicotine (0.001, 0.01, or 0.1 mM). In conclusion, despite similar increases in vascular wall superoxide production with tobacco and non-tobacco SS smoke, only the tobacco SS smoke extracts affected endothelium-dependent vasorelaxation. Nicotine alone does not reproduce the effects seen with tobacco SS smoke, suggesting that the acute endothelial toxicity of passive smoking cannot simply be ascribed to a nicotine-dependent mechanism.

[What are the alternatives to betablockers in 2009?]. / Quelles alternatives aux bêtabloquants en 2009?

Betablockers reduce mortality by 30% after a myocardial infarction. The anti anginal effects of betablockers are also very well established. They improve survival after a non cardiac surgery in patients at high cardiovascular risk. Atenolol should nevertheless be avoided for primary cardiovascular protection in patients with hypertension older than 55 yrs. This may not apply to more selective betablockers, or betablockers with vasodilator effects. We also now have another bradycardic agent, ivabradine, which may prove very useful in heart failure patients who cannot tolerate a betablocker.

Ecology of the cardiovascular system: A focus on air-related environmental factors.

Cardiology is a newcomer to environmental sciences. We aim to propose an original review of the scientific evidence regarding the effects of the environment on cardiovascular health. We report first influences of air-related environmental factors. Air temperature has a strong influence on cardiovascular mortality characterized by a V-like relationship confirming that both cold and hot periods have negative cardiovascular impacts. Furthermore, dynamic changes in temperature are likely more important than the absolute air temperature level. Cardiovascular reactions to air temperature are predominantly driven by increase in sympathetic tone. Indoor pollutants are mainly represented by smoke from cooking stoves and environmental tobacco smoke (ETS), and both are associated with increased cardiovascular mortality and morbidity. ETS is characterized by a curvilinear dose-effect relationship, showing already a significant effect even at low level of exposure and no threshold in effect appearance. Underlying ETS pathophysiology involves both effects of nicotinic stimulus on the sympathetic system and vascular oxidative stress. Smoking bans, as mitigation measures, were associated with a decrease in cardiovascular events. Long-term exposure to particulate air pollution was more recently recognized as an independent risk factor of cardiovascular mortality. Short-term increases in air pollution were also associated with an increased risk of myocardial infarction, stroke, and acute heart failure. Numerous experimental studies demonstrated that air pollution promotes a systemic vascular oxidative stress reaction followed by endothelial dysfunction, monocyte activation, and some proatherogenic changes of lipoproteins. Furthermore, air pollution favors thrombus formation as a result of increase in coagulation factors and platelet activation. Further studies are required to confirm that stricter air quality regulation or antioxidant regimen translate into some clinical benefits. In conclusion, ambient air temperature and pollution are major contributors to cardiovascular diseases. Improving air quality is now part of cardiovascular prevention.

[Physiopathology of heart failure: experimental model and therapeutic effects]. / Physiopathologie de l'insuffisance cardiaque : modèle expérimental et effets thérapeutiques.

Studies have shown the importance of heart rate variability alterations as a marker of neurohumoral dysregulation and haemodynamic derangements in experimental heart failure. Other studies have also revealed the importance of enhanced sympathetic nerve traffic and chemoreflex dysregulation in patients with pulmonary hypertension. Furthermore, the lack of favorable effects of beta mimetic agents on long term survival in heart failure patients may implicate an absence of sympathoinhibition, possibly related to a sensitization of the peripheral chemoreceptors. Sympathetic hyperactivity is however reduced by cardiac resynchronisation therapy. Last, a comparison of sympathetic nerve traffic during normoxia and hyperoxia in heart transplant recipients, essential hypertensive patients and control subjects has revealed that transplantation does not normalize peripheral chemoreflex hyperactivity and hypersensitivity. This mechanism contributes to blood pressure elevation and exercise hyperpnea in cardiac transplant recipients.

Effects of aging and cardiac denervation on heart rate variability during sleep.

BACKGROUND: Cardiac vagal predominance increases the RR interval and RR high-frequency (HF) variability during non-rapid eye movement (non-REM) sleep (stages I through IV) in young subjects. Aging suppresses deep sleep, but effects of age-related changes in sleep architecture on RR are unknown. Whether mechanical effects of changes in the breathing pattern on the sinus node during sleep affect RR variability is unclear. METHODS AND RESULTS: Polygraphic sleep recordings and RR and RR spectral profiles were determined in 8 young (22.5+/-3.3 years) and 8 older (55.0+/-7.3 years) healthy volunteers. HF oscillations in RR of 8 cardiac-denervated heart transplant recipients determined mechanical effects of respiration on the sinoatrial node during sleep. Transition from wakefulness to non-REM sleep increased the RR interval in young and older subjects and increased the HF variability of RR in the young (P:<0.05) but not in the older subjects. Older subjects disclosed a faster RR (P:<0.01) and a lower HF variability (P:<0.05) during non-REM sleep than the young subjects. Aging did not affect light and REM sleep but decreased deep sleep (stage IV) from 39+/-23 to 6+/-6 minutes (P:<0.001). Reduction in sleep stage IV with aging blunted the increase in RR and in RR HF variability during non-REM sleep (r>0.55, P:<0.05). Transition from wakefulness to non-REM sleep doubled the markedly reduced HF variability of RR in the heart transplant recipients (P:<0.05). CONCLUSIONS: Disappearance of deep sleep with aging impairs nocturnal increase in cardiac vagal activity. Mechanical effects of changes in breathing pattern during sleep favor increases in HF oscillations of the RR interval during non-REM sleep.

Enhanced sympathetic and ventilatory responses to central chemoreflex activation in heart failure.

BACKGROUND: Sympathetic activation and respiratory abnormalities may each be implicated in the pathophysiology of congestive heart failure (CHF). Chemoreflexes are an important mechanism regulating both sympathetic drive and breathing. We therefore tested the hypothesis that chemoreflex function is altered in CHF. METHODS AND RESULTS: We compared ventilatory, sympathetic, heart rate, and blood pressure responses to hypoxia, hypercapnia, and the cold pressor test in 9 patients with CHF and 9 control subjects matched for age and body mass index. Baseline muscle sympathetic nerve activity (MSNA) was higher in the patients with CHF compared with control subjects (47+/-8 versus 23+/-3 bursts per minute, P<0.01). During hypercapnia, patients with CHF had greater increases in minute ventilation (6.7+/-1.4 versus 2.7+/-0.9 L/min, P=0.03) and heart rate (7.0+/-2.1 versus 0.6+/-1.2 bpm, P=0.02). Despite higher ventilation, which inhibits sympathetic activity, the MSNA increase in patients with CHF was also greater than that in control subjects (58+/-12% versus 21+/-9%, P=0.03). Ventilatory, autonomic, and blood pressure responses to hypoxia and the cold pressor test in CHF patients were not different from those in control subjects. CONCLUSIONS: Chronic heart failure is characterized by a selective potentiation of ventilatory and sympathetic responses to central chemoreceptor activation by hypercapnia.

Independent association between plasma leptin levels and heart rate in heart transplant recipients.

BACKGROUND: Leptin, the protein product of the ob gene, has been linked to a faster heart rate in animal and human studies. The interaction between leptin and heart rate in the denervated heart is not known. Therefore, we studied the relationship between plasma leptin levels and heart rate in heart transplant recipients. METHODS AND RESULTS: We studied 32 male patients (mean age, 56.5+/-9.3 years; range, 41 to 74 years) after orthotopic heart transplantation. All subjects underwent a physical examination, anthropometric measurements, blood chemistry analysis, and office blood pressure measurements. A blood sample was collected from each subject while fasting. In univariate analysis, heart rate was related to leptin levels (r=0.47, P=0.007) but heart rate was not related to systolic or diastolic blood pressure, mean arterial pressure, body mass index, or catecholamines. Leptin levels were only strongly associated with heart rate and body mass index (r=0.73, P<0.0001). In multivariate analysis, heart rate was independently and positively associated with leptin levels (F=2.61, P=0.017). We also observed a strong, independent association between leptin levels and body mass index (F=5.8, P<0.00001). CONCLUSIONS: We show an independent association between leptin levels and heart rate in heart transplant recipients. We speculate that this may be due, in part, to a direct effect of leptin on heart rate, conceivably mediated through cardiac leptin receptors.

Differential characteristics of neural circulatory control: early versus late after cardiac transplantation.

BACKGROUND: Reappearance of low-frequency (LF) (+/-0.10 Hz) oscillations in RR interval (RR) after cardiac transplantation is indicative of sympathetic efferent reinnervation. We hypothesized that restored LF oscillations in RR in heart transplant recipients (HTRs) are linked to oscillations in muscle sympathetic nerve traffic (MSNA). METHODS AND RESULTS: RR, RR variability, and MSNA were recorded 5+/-2 months (n=7, short-term HTRs) and 138+/-8 months (n=7, long-term HTRs) after heart transplantation and compared with matched hypertensive patients (n=7). A coherence function determined the coupling between LF oscillations in MSNA and RR. RR variance did not differ between short-term and long-term HTRs. However, LF variability was only 1+/-0.5 ms(2) in the short-term HTRs but was 15+/-8 ms(2) in the long-term HTRs (P<0.05). Normalized LF variability was also higher in the long-term HTRs (40+/-14 normalized unites) versus the short-term HTRs (6+/-3 normalized united, P<0.05) but did not differ from the LF variability of the hypertensive patients. Long-term HTRs were taking less cyclosporine (P<0.01) but had higher MSNA than the short-term HTRs (62+/-7 versus 31+/-7 burst/min, respectively, P<0.05). Coherence between LF oscillations in MSNA and RR was similar in the long-term HTRs (0.59+/-0.11) and the hypertensive patients (0.60+/-0.07) and was 3-fold greater than in the short-term HTRs (0.20+/-0.06, P<0.05). CONCLUSIONS: Cardiac reinnervation after long-term heart transplantation is characterized by a restoration of the coherence between LF oscillations in RR and MSNA. Higher MSNA in long-term than in short-term HTRs suggests that time elapsed after cardiac transplantation may be a major determinant of sympathetic excitation in heart transplant recipients.

Progressive aging does not alter the interaction between autonomic cardiac activity and delta EEG power.

OBJECTIVE: We tested the hypothesis that the reductions of the changes in the respective influence of the cardiac sympathetic and vagal activity control and delta EEG activity with aging alter the interactions between the heart rate variability (HRV) and the delta sleep EEG power band. METHODS: A polysomnography was performed on 16 healthy young men and 19 healthy middle-aged men across the first 3 NREM-REM cycles. Spectral analysis was applied to electrocardiogram and electroencephalogram recordings. High Frequency (HF(nu)) of HRV as well as the maximum of cross-spectrum, coherency, gain and phase shifts between HF(nu) and delta sleep EEG power band were compared between both groups. RESULTS: Young men experienced more deep sleep than middle-aged men (P<0.001). In middle-aged subjects, HF(nu) was lower than the HF(nu) of their younger counterparts (P<0.001), but they showed similar increases during NREM sleep and similar decreases during REM sleep as the young subjects. Cross-spectrum values, coherency, gain and phase shifts between HF(nu) and delta were identical between the two groups. Modifications in HF(nu) show parallel changes and precede changes in delta EEG band by a similar leads of 11+/-6min in young men and 9+/-7 min in middle-aged men (P=0.23). CONCLUSIONS: Reduced changes in the respective influence of the cardiac sympathetic and vagal activity and delta EEG activity with progressive aging do not alter the relationship and phase difference between changes in the relative predominant cardiac vagal activity and delta power in middle-aged men. SIGNIFICANCE: Interaction between the cardiac sympathetic and vagal activity with delta EEG activity is maintained in middle-aged men.

Quantitative analysis of the 24-hour blood pressure and heart rate patterns in young men.

To characterize the normal nycterohemeral blood pressure and heart rate profiles and to delineate the relative roles of sleep and circadian rhythmicity, we performed 24-hour ambulatory blood pressure monitoring with simultaneous polygraphic sleep recording in 31 healthy young men investigated in a standardized physical and social environment. Electroencephalographic sleep recordings were performed during 4 consecutive nights. Blood pressure and heart rate were measured every 10 minutes for 24 hours starting in the morning preceding the fourth night of recording. Sleep quality was not significantly altered by ambulatory blood pressure monitoring. A best-fit curve based on the periodogram method was used to quantify changes in blood pressure and heart rate over the 24-hour cycle. The typical blood pressure and heart rate patterns were bimodal with a morning acrophase (around 10:00 AM), a small afternoon nadir (around 3:00 PM), an evening acrophase (around 8:00 PM), and a profound nocturnal nadir (around 3:00 AM). The amplitude of the nycterohemeral variations was largest for heart rate, intermediate for diastolic blood pressure, and smallest for systolic blood pressure (respectively, 19.9%, 14.1%, and 10.9% of the 24-hour mean). Before awakening, a significant increase in blood pressure and heart rate was already present. Recumbency and sleep accounted for 65-75% of the nocturnal decline in blood pressure, but it explained only 50% of the nocturnal decline in heart rate. Thus, the combined effects of postural changes and the wake-sleep transition are the major factors responsible for the 24-hour rhythm in blood pressure. In contrast, the 24-hour rhythm of heart rate may reflect an endogenous circadian rhythm, amplified by the effect of sleep. We conclude that modulatory factors different from those controlling nycterohemeral changes in blood pressure influence the 24-hour variation in heart rate.

Twenty-four-hour blood pressure and heart rate profiles in humans. A twin study.

To delineate the relative roles of genetic and environmental factors on physiological variations of blood pressure and heart rate, we performed 24-hour ambulatory blood pressure monitorings with simultaneous polygraphic sleep recordings in 28 monozygotic and 16 dizygotic healthy young male twin pairs investigated in a standardized physical and social environment. Blood pressure and heart rate were measured every 10 minutes for 24 hours. A best-fit curve based on the periodogram method was used to quantify changes in blood pressure and heart rate over the 24-hour span. Surprisingly, monozygotic twins as a group tended to have higher blood pressure values than dizygotic twins, and this difference reached the level of significance for daytime systolic blood pressure (P < .005). Although environmental influences largely controlled the mean levels and characteristics of the 24-hour systolic blood pressure variations, significant genetic effects were demonstrated for the mean levels and 24-hour patterns of diastolic blood pressure and heart rate. For both diastolic blood pressure and heart rate, the genetic effects concerned largely the same characteristics of the 24-hour profiles: the 24-hour mean, the daytime mean, the value of the evening acrophase, and the value of the major acrophase. Moreover, there was a strong genetic influence for the amplitude of the 24-hour rhythm of heart rate.

Effects of alcohol on sympathetic activity, hemodynamics, and chemoreflex sensitivity.

Alcohol intake has been shown to worsen obstructive sleep apnea and increase nocturnal hypoxemia. The mechanisms of this action are unclear. Animal studies suggest that a reduction in chemoreflex sensitivity may be implicated. Using a double-blind, randomized, vehicle-controlled design, we tested the hypothesis that oral alcohol intake depresses chemoreflex sensitivity in humans. We examined the effects of oral alcohol intake (1.0 g/kg body wt) on blood pressure, heart rate, heart rate variability, muscle sympathetic nerve activity, forearm vascular resistance, and minute ventilation in 16 normal male subjects. Peripheral and central chemoreflex sensitivity were measured in response to hypoxia (n = 10) and hypercapnia (n = 6), respectively. Plasma alcohol increased from 0 to 23.2 +/- 1.5 mmol/L (107 +/- 7 mg/dL) at 60 minutes and 20.2 +/- 1 mmol/L (93 +/- 4 mg/dL) at 85 minutes after alcohol intake (P < .0001). Alcohol induced an increase in heart rate from 59 +/- 2 to 66 +/- 2 beats per minute (P < .01) and increased the ratio of low- to high-frequency variability of heart rate (P < .05). Although alcohol increased sympathetic nerve activity by up to 239 +/- 22% of baseline values (P < .01), forearm vascular resistance after alcohol was lower than that after vehicle (P < .05). Blood pressure did not increase compared with the vehicle session. Oxygen saturation during hypoxia after alcohol was 4 +/- 1% lower than it was during hypoxia after vehicle (P < .05) although arterial blood PO2 was unchanged. Alcohol did not affect the cardiovascular, sympathetic, or ventilatory responses to either hypoxia or hypercapnia. Acute increases in plasma alcohol increase heart rate and sympathetic nerve activity; blood pressure is not increased, probably because of vasodilator effects of alcohol. Alcohol does not alter chemoreflex responses to hypoxia or hypercapnia; thus, alterations in chemoreflex sensitivity are unlikely to explain the effects of alcohol on sleep apnea. Alcohol may reduce the affinity of hemoglobin for oxygen.