Baroreflex sensitivity assessed with the sequence method is associated with ventricular arrhythmias in patients implanted with a defibrillator for the primary prevention of sudden cardiac death.

BACKGROUND: Left ventricular ejection fraction lacks accuracy in predicting sudden cardiac death, resulting in unnecessary implantation of cardioverter defibrillators for the primary prevention of sudden cardiac death. Baroreflex sensitivity could help to stratify patients at risk of ventricular arrhythmia. AIM: To assess the association between cardiac baroreflex sensitivity and ventricular arrhythmias in patients implanted with an implantable cardioverter defibrillator for the primary prevention of sudden cardiac death after myocardial infarction. METHODS: This case-control single-centre study took place between 2015 and 2016. Cases (n=10) had experienced ventricular arrhythmias treated by the implantable cardioverter defibrillator in the previous 3 years; controls (n=22) had no arrhythmia during the same period. Baroreflex sensitivity was assessed using the temporal sequence method (mean slope) and cross-spectral analysis (low-frequency gain and high-frequency gain). RESULTS: The mean age was 65 years; 94% of the patients were men. 24-hour Holter electrocardiogram autonomous nervous system variables, left ventricular ejection fraction and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) concentration did not differ between cases and controls. The mean slope was lower in cases than in controls (8 vs. 15ms/mmHg [P=0.009] in the supine position; 7 vs. 12ms/mmHg [P=0.038] in the standing position). The mean slope in the supine position was still significantly different between groups after adjustment for age, left ventricular ejection fraction and NT-proBNP (P=0.03). By comparison, low-frequency gain and high-frequency gain did not differ between groups in either the supine or the standing position. CONCLUSION: Patients with ventricular arrhythmias had a lower mean slope compared with those who were free of arrhythmia. A prospective study is needed to confirm this association.

Increased carotid stiffness and remodelling at early stages of chronic kidney disease.

OBJECTIVE: Increased carotid stiffness and remodelling is reported in patients with moderate and advanced chronic kidney disease (CKD) and is associated with cardiovascular events. Here, we tested the hypothesis that carotid artery alterations start earlier, during mild CKD. METHODS: Within the Paris Prospective Study 3, a large prospective observational survey of nonreferred people aged 50-75 who received an extensive health check-up, there were 294 participants with glomerular filtration rate (GFR) of at least 45 and less than 60 ml/min per 1.73 m (Stage 3A CKD), 840 participants with GFR 60-89 ml/min per 1.73 m with proteinuria (Stage 2 CKD), 4666 participants with GFR 60-89 ml/min per 1.73 m without proteinuria and 3317 individuals with GFR at least 90 ml/min per 1.73 m at study recruitment. Carotid artery measurements were performed using a high-resolution echotracking device. RESULTS: Compared with patients with GFR at least 90 ml/min per 1.73 m, the carotid distensibility and strain progressively decreased (P for trend <0.0001), whereas carotid stiffness progressively increased (P for trend <0.0001) across GFR categories starting at early stage from GFR 60-89 ml/min per 1.73 m without proteinuria. Higher Young's elastic modulus was observed only for Stage 3A CKD, whereas carotid internal diastolic diameter did not differ between groups. CONCLUSION: The large arterial stiffening starts early during CKD, even in participants with a very mild reduction in renal function.

EEG profiles during general anesthesia in children: A comparative study between sevoflurane and propofol.

BACKGROUND: In this prospective study, we describe the electroencephalographic (EEG) profiles in children anesthetized with sevoflurane or propofol. METHODS: Seventy-three subjects (11 years, range 5-18) were included and randomly assigned to two groups according to the anesthetic agent. Anesthesia was performed by target-controlled infusion of propofol (group P) or by sevoflurane inhalation (group S). Steady-state periods were performed at a fixed randomized concentration between 2, 3, 4, 5, and 6 µg.ml-1 of propofol in group P and between 1, 2, 3, 4, and 5% of sevoflurane in group S. Remifentanil was continuously administered throughout the study. Clinical data, Bispectral Index (BIS), and raw EEG were continuously recorded. The relationship between BIS and anesthetic concentrations was studied using nonlinear regression. For all steady-state periods, EEG traces were reviewed to assess the presence of epileptoid signs, and spectral analysis of raw EEG was performed. RESULTS: Under propofol, BIS decreased monotonically and EEG slowed down as concentrations increased from 2 to 6 µg.ml-1 . Under sevoflurane, BIS decreased from 0% to 4% and paradoxically rose from 4% to 5% of expired concentration: this increase in BIS was associated with the occurrence of fast oscillations and epileptoid signs on the EEG trace. Propofol was associated with more delta waves and burst suppression periods compared to sevoflurane. CONCLUSION: Under deep anesthesia, the BIS and electroencephalographic profiles differ between propofol and sevoflurane. For high concentrations of sevoflurane, an elevated BIS value may be interpreted as a sign of epileptoid patterns or EEG fast oscillations rather than an insufficient depth of hypnosis.

Sympathetic baroreceptor regulation during hypoxic hypotension in humans: new insights.

BACKGROUND: Baroreceptor activation by a continuous infusion of phenylephrine selectively abolishes the muscle sympathetic nerve activity (MSNA) response to hypoxia in humans. Baroreceptor deactivation enhances the MSNA rise during hypoxia in animals. Whether this is true in humans is unknown and was tested in the present study. METHODS: We assessed MSNA responses elicited by isocapnic hypoxia (10% O2 in N2) during baroreflex loading and unloading with phenylephrine and nitroprusside, respectively, in 19 healthy volunteers. The study was randomized and placebo-controlled. RESULTS: Phenylephrine and nitroprusside increased and decreased, respectively, blood pressure during normoxia and hypoxia, whereas the reverse occurred for heart rate and MSNA (all P < 0.001 vs. placebo). As compared with normoxia, cardiac barosensitivity decreased during the infusion of placebo and nitroprusside in the presence of hypoxia, as well as sympathetic barosensitivity during the infusion of nitroprusside (all P < 0.05). Three patients even disclosed a reduction in arterial pressure, which became apparent at the third minute of hypoxia and worsened steadily thereafter (SBP: 91 ±â€Š7 mmHg; DBP 47 ±â€Š9 mmHg), in spite of a gradual rise in heart rate of 20 ±â€Š4 bpm. Changes in baroreceptor loading conditions did not affect ventilation during normoxia and hypoxia. CONCLUSION: Cardiac and sympathetic baroreceptor sensitivity decrease during baroreceptor unloading in the presence of peripheral chemoreceptor activation. Normal humans have limited reflex capabilities to sustain simultaneous reductions in oxygen and pressure, and may experience hemodynamic instability episodes in such condition.

The Neural Baroreflex Pathway in Subjects With Metabolic Syndrome: A Sub-Study of the Paris Prospective Study III.

The mechanisms that link metabolic syndrome (MetS) to increased cardiovascular risk are incompletely understood. We examined whether MetS is associated with the neural baroreflex pathway (NBP) and whether any such associations are independent of blood pressure values.This study involved the cross-sectional analysis of data on 2835 subjects aged 50 to 75 years from the Paris Prospective Study 3. The prevalence of MetS was defined according to the American Heart Association/National Heart Blood and Lung Institute definition. NBP values were calculated from the fluctuation of the common carotid distension rate and heart rate using fast Fourier transformation and cross-spectral analysis.The prevalence of MetS was 20.1% in men and 10.4% in women. Compared with controls, subjects with MetS (≥3 components), and those at risk for MetS (1-2 components) had lower NBP (-5.3% and -2.3%, respectively) and higher carotid stiffness (+13.5% and +6.8%, respectively). The negative association between MetS components and NBP was confirmed, even after adjustment for age, sex, and carotid stiffness. After stratification for blood pressure (BP) levels, NBP was reduced only in MetS subjects and those at risk with high BP. The NBP was positively associated with carotid stiffness in controls and subjects at risk for MetS. This association was lost in subjects with MetS, regardless of BP levels.Subjects with MetS had reduced NBP values. The role of BP is fundamental in the reduction of NBP. The mechanisms that link carotid stiffness and NBP are inactive in subjects with MetS, independent of BP levels.

Visualizing oxidative stress-induced depression of cardiac vagal baroreflex by MRI/DTI in a mouse neurogenic hypertension model.

A clinical hallmark of hypertension is impairment of the cardiac vagal baroreflex, which maintains stable blood pressure and heart rate under physiological conditions. There is also evidence that oxidative stress in the brain is associated with neurogenic hypertension. We tested the hypothesis that an augmented superoxide level in the nucleus tractus solitarii (NTS), the terminal site of baroreceptor afferents, contributes to the depression of cardiac vagal baroreflex by disrupting the connectivity between the NTS and the nucleus ambiguus (NA), the origin of the vagus nerve, during neurogenic hypertension. An experimental model of neurogenic hypertension that employed intracerebroventricular infusion of angiotensin II in male adult C57BL/6 mice was used. Based on tractographic evaluations using magnetic resonance imaging/diffusion tensor imaging of the medulla oblongata in the brain stem, we found that the connectivity between the NTS and NA was disrupted in neurogenic hypertension, concurrent with impairment of the cardiac vagal baroreflex as detected by radiotelemetry. We further found that the disrupted NTS-NA connectivity was reversible, and was related to oxidative stress induced by augmented levels of NADPH oxidase-generated superoxide in the NTS. We conclude that depression of the cardiac vagal baroreflex induced by oxidative stress in the NTS in the context of neurogenic hypertension may be manifested in the form of dynamic alterations in the connectivity between the NTS and NA.

Involvement of the dorsomedial hypothalamus and the nucleus tractus solitarii in chronic cardiovascular changes associated with anxiety in rats.

Anxiety disorders in humans reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). Both may contribute to sudden death. To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions on four consecutive days. Five days later, the rats were found to be in an anxiety-like state. At this time point, we analysed HRV and BRS in the defeated rats, with or without treatment with the anxiolytic chlordiazepoxide (CDZ). HRV was reduced after social defeat, due to changes in the autonomic balance favouring the sympathetic over the parasympathetic component. Spontaneous and pharmacological baroreflex gains were also reduced. CDZ abolished anxiety-like symptoms as well as HRV and BRS alterations. Inhibition of the dorsomedial hypothalamus (DMH) with muscimol reversed all cardiovascular alterations, whereas blockade of the nucleus tractus solitarii (NTS) 5-HT3 receptor by the local or systemic administration of granisetron restored only baroreflex gains and the parasympathetic component of HRV. In conclusion, repeated social defeat in the rat lead to an anxiety-like state that was associated with lasting reduction in HRV and baroreflex gains. The DMH and the NTS were responsible for these chronic cardiovascular alterations. These regions may therefore constitute new therapeutic targets for reducing cardiac dysfunction and fibrillation in anxiety disorders.

Cardiovascular rhythms and cardiac baroreflex sensitivity in AT(1A) receptor gain-of-function mutant mice.

A mutant mouse expressing a gain-of-function of the AT(1A) angiotensin II receptor was engineered to study the consequences of a constitutive activation of this receptor on blood pressure (BP). Cardiovascular rhythms and spontaneous cardiac baroreflex sensitivity (BRS) were evaluated using telemetric BP recordings of five transgenic (AT(1A)MUT) and five wild (AT(1A)WT) mice. The circadian rhythms were described with the Chronos-Fit program. The gain of the transfer function between systolic BP (SBP) and pulse intervals used to estimate the spontaneous BRS (ms/mmHg) was calculated in the low frequency (0.15-0.60 Hz) band. Transgenic AT(1A)MUT exhibited higher BP and heart rate (HR) levels compared to controls (SBP AT(1A)MUT 134.6 +/- 5.9 mmHg vs. AT(1A)WT 110.5 +/- 5.9; p < 0.05; HR AT(1A)MUT 531.0 +/- 14.9 vs. AT(1A)WT 454.8 +/- 5.4 beats/min; p = 0.001). Spontaneous BRS was diminished in transgenic mice (AT(1A)MUT 1.23 +/- 0.17 ms/mmHg vs. AT(1A)WT 1.91 +/- 0.18 ms/mmHg; p < 0.05). Motor activity did not differ between groups. These variables exhibited circadian changes, and the differences between the strains were maintained throughout the cycle. The highest values for BP, HR, and locomotor activity were observed at night. Spontaneous BRS varied in the opposite direction, with the lowest gain estimated when BP and HR were elevated (i.e., at night, when the animals were active). It is likely the BP elevation of the mutant mice results from the amplification of the effects of AngII at different sites. Future studies are necessary to explore whether AT(1A) receptor activation at the central nervous system level effectively contributed to the observed differences.

Tuning of the sequence technique.

The sequence method was first described by Di Rienzo in cats and applied in different species including humans. Until now, no systematic study of spontaneous baroreflex sensitivity (BRS) has been performed by the sequence method in mice. This study aimed to characterize the best estimates of BRS using the sequence method by tuning all the possible parameters, specifically, the number of beats involved in a sequence, the minimal changes in blood-pressure (BP) ramps, and the minimal changes in pulse-interval (PI) ramps. Also, the relevance to set a minimal correlation coefficient in the regression line between BP and PI was tested. An important point was the delay to be applied between BP and PI. This delay represents the physiological time for the baroreflex loop to efficiently correct the BP variations.

Tissue kallikrein deficiency and renovascular hypertension in the mouse.

The kallikrein kinin system (KKS) is involved in arterial and renal functions. It may have an antihypertensive effect in both essential and secondary forms of hypertension. The role of the KKS in the development of two-kidneys, one-clip (2K1C) hypertension, a high-renin model, was investigated in mice rendered deficient in tissue kallikrein (TK) and kinins by TK gene inactivation (TK-/-) and in their wild-type littermates (TK+/+). Four weeks after clipping the renal artery, blood flow was reduced in the clipped kidney (2K1C-TK+/+: -90%, 2K1C-TK-/-: -93% vs. sham-operated mice), and the kidney mass had also decreased (2K1C-TK+/+: -65%, 2K1C-TK-/-: -66%), whereas in the unclipped kidney, blood flow (2K1C-TK+/+: +19%, 2K1C-TK-/-: +17%) and kidney mass (2K1C-TK+/+: +32%, 2K1C-TK-/-: +30%) had both increased. The plasma renin concentration (2K1C-TK+/+: +78%, 2K1C-TK-/-: +65%) and renal renin content of the clipped kidney (2K1C-TK+/+: +58%, 2K1C-TK-/-: +65%) had increased significantly. There was no difference for these parameters between 2K1C-TK+/+ and 2K1C-TK-/- mice. Blood pressure monitored by telemetry and by plethysmography, rose immediately after clipping in both genotypes, and reached similar levels (2K1C-TK+/+: +24%, 2K1C-TK-/-: +21%). 2K1C-TK+/+ and 2K1C-TK-/- mice developed similar concentric left ventricular hypertrophy (+24% and +17%, respectively) with normal cardiac function. These findings suggest that in the context of chronic unilateral reduction in renal blood flow, TK and kinins do not influence the trophicity of kidneys, the synthesis and secretion of renin, blood pressure increase, and cardiac remodeling due to renin angiotensin system activation.

Acute effects of sildenafil on flow mediated dilatation and cardiovascular autonomic nerve function in type 2 diabetic patients.

BACKGROUND: Sildenafil, frequently used as on demand medication for the treatment of erectile dysfunction (ED), has been suggested to improve endothelial function but also to alter blood pressure (BP) and induce sympathetic activation. In people with type 2 diabetes mellitus (T2DM), a high-risk population, the safety profile and the effects on endothelial function of a maximal sildenafil dose (100 mg) have not been investigated and therefore constituted the aim of our study. METHODS: A double-blind, placebo-controlled, cross-over trial using a single dose of 100 mg sildenafil or placebo has been conducted in 40 subjects with T2DM without known CVD. Haemodynamic parameters, flow mediated dilatation (FMD) in brachial artery, cardiovascular autonomic function tests and spontaneous baroreflex sensitivity (BRS) were measured. RESULTS: Sixty minutes after administration of sildenafil but not placebo, a fall of supine systolic blood pressure (SBP) (-5.41 +/- 1.87 vs. + 0.54 +/- 1.71 mmHg) and diastolic blood pressure (DBP) (-4.46 +/- 1.13 vs. + 0.89 +/- 0.94 mmHg), as well as orthostatic SBP (-7.41 +/- 2.35 vs. + 0.94 +/- 2.06 mmHg) and DBP (-5.65 +/- 1.45 vs. + 1.76 +/- 1.00 mmHg) during standing occurred, accompanied by an increase in heart rate (+1.98 +/- 0.69 vs. - 2.42 +/- 0.59 beats/min) (all p < 0.01 vs. placebo). Changes in BP to standing up, FMD, time domain and frequency domain indices of heart rate variability (HRV) and BRS were comparable between sildenafil and placebo. CONCLUSIONS: Sildenafil administered at a maximum single dose to T2DM men results in a mild increase in heart rate and decrease in BP, but it induces neither an acute improvement of FMD nor any adverse effects on orthostatic BP regulation, HRV and BRS.

Tuba players reproduce a Valsalva maneuver while playing high notes.

Playing wind instruments requires expiratory efforts. Blowing low notes on a tuba means a low resistance to expiration while playing high notes requires a strenuous expiratory strain. The resulting high intrathoracic pressure may reproduce a Valsalva maneuver. Ten tuba players were asked to blow medium loud long (15 seconds) notes at three different pitches (low, middle, and high) and to perform Valsalva maneuvers at 10, 40, and 60 mmHg. Blood pressure (BP) was measured continuously with a Finapres monitor. The four classic phases of the Valsalva maneuver were reproduced with the notes. The expiratory effort produced systolic BP and pulse pressure falls reaching about 24 mmHg with the high note or the Valsalva 60. BP and pulse pressure falls were linearly related to stroke volume reductions. Reflex heart rate (HR) changes were inversely related to BP falls, with maximal increases for the high notes (24 beats/minute) and Valsalva 60 (33 beats/minute). High baroreflex sensitivity was associated with a high HR response. Total peripheral resistance was reflexly elevated to counteract cardiac output reductions. During rebreathing, BP overshoots reached 30 mmHg for the high note and 53 mmHg for the Valsalva 60. Altogether, these findings indicate that blowing notes on a tuba reproduces the cardiovascular changes seen with a Valsalva maneuver with the effects of blowing high notes being close to a classic (40 mmHg) Valsalva maneuver. In addition, the baroreflex sensitivity might be a predictor of the ability to surmount the BP intolerance that could occur during wind instrument playing.

Effects of atropine on the time and frequency domain estimates of blood pressure and heart rate variability in mice.

1. Indices quantifying blood pressure (BP) and heart rate (HR) variability have been recently developed and may be used to assess the contribution of the autonomic nervous system to cardiovascular fluctuations. 2. Cardiovascular variables were measured in eight conscious mice equipped with a BP telemetric device. Each recording session was conducted when the mice were at rest and included a control period, an injection of atropine methylnitrate (2 mg/kg) and a post-treatment recording. 3. Time domain indices were the mean pulse interval (PI) and NN (the normal-to-normal intervals), mean HR, standard deviation of PI (SDNN), the square root of the mean of the sum of the squares of differences between adjacent PI (RMSSD) and the pNN8 (NN8 count divided by the number of NN intervals). Frequency domain indices of HR variability were the low frequency (LF) zone (0.15-0.60 Hz) and the high frequency (HF, respiratory sinus arrhythmia) zone (2.5-5.0 Hz) of the PI power spectrum. The time domain index of spontaneous baroreflex sensitivity (BRS) was the slope of the linear PI and systolic BP relationship obtained using the sequence technique. The frequency domain indices of BRS were the gain of the transfer function between systolic BP and PI in the LF and HF bands. 4. Atropine markedly affected these variables, illustrating vagal predominance under resting conditions in mice. The preferable time and frequency domain indices for quantifying the vagal contribution to HR variability were the pNN8 and the LF gain.

Accelerated arterial stiffening and gene expression profile of the aorta in patients with coronary artery disease.

BACKGROUND: Hypertension and chronic renal failure (CRF) are considered models of accelerated arterial stiffening. Arterial stiffness increases further when CRF is associated with hypertension. We hypothesized that, in patients with mild CRF, aortic gene expression profile would include genes involved in arterial calcifications and enlargement. METHOD: We analysed human aorta with the 'GeneChip Microarray' technology, in patients with or without CRF, scheduled for a coronary artery bypass graft. RESULTS: Nine of 25 patients had high-quality RNA and were included in the study. Among the 101 transcripts differentially expressed between CRF patients and controls, 97 transcripts were overexpressed in CRF patients. Two genes had the highest overexpression in CRF patients: lumican (LUM), involved in the regulation of collagen fibrillogenesis; and ornithine decarboxylase (ODC1), involved in polyamine biosynthesis, smooth muscle cell growth and proliferation. Immunohistochemical staining revealed an increased amount of LUM and ODC1 in the vascular smooth muscle cells (VSMCs) of CRF compared to non-CRF aortic sections. Eight genes were implicated in the regulation of the cytoskeleton (including capping protein muscle Z-line 1 alpha and moesin) and cell migration, and five genes were implicated in extracellular matrix function and apoptosis. A trend towards an upregulation of candidate genes involved in arterial calcifications was observed in CRF patients, but did not reach statistical significance. Carotid-femoral pulse wave velocity was not correlated with gene expression level. CONCLUSION: In conclusion, these results show that patients at an early stage of CRF have a specific gene expression profile of aortic tissue and suggest that genes implicated in collagen fibrillogenesis, and VSMCs migration and proliferation, particularly LUM and ODC1, may play a role.

Applicability of recent methods used to estimate spontaneous baroreflex sensitivity to resting mice.

Short-term blood pressure (BP) variability is limited by the arterial baroreflex. Methods for measuring the spontaneous baroreflex sensitivity (BRS) aim to quantify the gain of the transfer function between BP and pulse interval (PI) or the slope of the linear relationship between parallel BP and PI changes. These frequency-domain (spectral) and time-domain (sequence) techniques were tested in conscious mice equipped with telemetric devices. The autonomic relevance of these indexes was evaluated using pharmacological blockades. The significant changes of the spectral bandwidths resulting from the autonomic blockades were used to identify the low-frequency (LF) and high-frequency (HF) zones of interest. The LF gain was 1.45 +/- 0.14 ms/mmHg, with a PI delay of 0.5 s. For the HF gain, the average values were 2.0 +/- 0.19 ms/mmHg, with a null phase. LF and HF bands were markedly affected by atropine. On the same 51.2-s segments used for cross-spectral analysis, an average number of 26.4 +/- 2.2 slopes were detected, and the average slope in resting mice was 4.4 +/- 0.5 ms/mmHg. Atropine significantly reduced the slopes of the sequence method. BRS measurements obtained using the sequence technique were highly correlated to the spectral estimates. This study demonstrates the applicability of the recent methods used to estimate spontaneous BRS in mice. There was a vagal predominance in the baroreflex control of heart rate in conscious mice in the present conditions.

Differential effects of metaboreceptor and chemoreceptor activation on sympathetic and cardiac baroreflex control following exercise in hypoxia in human.

Muscle metaboreceptors and peripheral chemoreceptors exert differential effects on the cardiorespiratory and autonomic responses following hypoxic exercise. Whether these effects are accompanied by specific changes in sympathetic and cardiac baroreflex control is not known. Sympathetic and cardiac baroreflex functions were assessed by intravenous nitroprusside and phenylephrine boluses in 15 young male subjects. Recordings were performed in random order, under locally circulatory arrested conditions, during: (1) rest and normoxia (no metaboreflex and no chemoreflex activation); (2) normoxic post-handgrip exercise at 30% of maximum voluntary contraction (metaboreflex activation without chemoreflex activation); (3) hypoxia without handgrip (10% O2 in N2, chemoreflex activation without metaboreflex activation); and (4) post-handgrip exercise in hypoxia (chemoreflex and metaboreflex activation). When compared with normoxic rest (-42 +/- 7% muscle sympathetic nerve activity (MSNA) mmHg(-1)), sympathetic baroreflex sensitivity did not change during normoxic post-exercise ischaemia (PEI; -53 +/- 9% MSNA mmHg(-1), P = 0.5) and increased during resting hypoxia (-68 +/- 5% MSNA mmHg(-1), P < 0.01). Sympathetic baroreflex sensitivity decreased during PEI in hypoxia (-35 +/- 6% MSNA mmHg(-1), P < 0.001 versus hypoxia without exercise; P = 0.16 versus normoxic PEI). Conversely, when compared with normoxic rest (11.1 +/- 1.7 ms mmHg(-1)), cardiac baroreflex sensitivity did not change during normoxic PEI (8.3 +/- 1.3 ms mmHg(-1), P = 0.09), but decreased during resting hypoxia (7.3 +/- 0.8 ms mmHg(-1), P < 0.05). Cardiac baroreflex sensitivity was lowest during PEI in hypoxia (4.3 +/- 1 ms mmHg(-1), P < 0.01 versus hypoxia without exercise; P < 0.001 versus normoxic exercise). The metaboreceptors and chemoreceptors exert differential effects on sympathetic and cardiac baroreflex function. Metaboreceptor activation is the major determinant of sympathetic baroreflex sensitivity, when these receptors are stimulated in the presence of hypoxia.

Specific serotonin reuptake inhibition in major depressive disorder adversely affects novel markers of cardiac risk.

There exists a growing body of evidence linking depression with cardiovascular events, although the mechanisms responsible remain unknown. We investigated the role of the autonomic nervous system and inflammation in the link between coronary heart disease and major depressive disorder (MDD), and examined the cardiac risk modification following pharmacological treatment of depression. We measured cardiac baroreflex function, heart rate variability, pulse pressure and high sensitivity C-reactive protein (hsCRP), all of which have an impact on cardiac risk, pre- and post-treatment in 25 patients with MDD, with no history of coronary heart disease, and in 15 healthy subjects. Treatment consisted of selective serotonin reuptake inhibitors for approximately 12 weeks. No significant differences were observed between untreated MDD patients and healthy subjects in blood pressure, heart rate, baroreflex sensitivity or heart rate variability. Pulse pressure and hsCRP, however, were significantly elevated in patients with MDD prior to treatment (p=0.023 and p=0.025, respectively). Moreover, while pharmacotherapy was effective in alleviating depression, surprisingly, each of cardiac baroreflex function, heart rate variability, pulse pressure and hsCRP was modified (p<0.05) in a manner likely to increase cardiac risk. In conclusion, this study demonstrated higher pulse pressure and hsCRP plasma levels in patients with MDD, which might contribute to increased cardiac risk. Following treatment vagal activity was reduced, as indicated by reductions in baroreflex sensitivity and heart rate variability, accompanied by increases in pulse pressure and plasma hsCRP levels. Mechanisms potentially responsible for generating cardiac risk in patients treated with selective serotonin reuptake inhibitors may need to be therapeutically targeted to reduce the incidence of coronary heart disease in this population.

Aortic stiffness and pulse pressure amplification in Wistar-Kyoto and spontaneously hypertensive rats.

In humans, increased body weight and arterial stiffness are significantly associated, independently of blood pressure (BP) level. The finding was never investigated in rodents devoid of metabolic disorders as spontaneously hypertensive rats (SHR). Using simultaneous catheterization of proximal and distal aorta, we measured body weight, intra-arterial BP, heart rate and their variability (spectral analysis), aortic pulse wave velocity (PWV), and systolic and pulse pressure (PP) amplifications in unrestrained conscious Wistar-Kyoto (WKY) rats and SHR between 6 and 24 wk of age. Aortic proximal systolic and diastolic pressure, PP, and mean BP were significantly higher in SHR than in WKY rats and increased significantly with age (with the exception of PP). PP amplification increased with age but did not differ between strains. PWV was significantly associated with heart rate variability. PWV was significantly higher (via two-way variance analysis) in SHR than in WKY rats (strain effect) and increased markedly with age in both strains (age effect). Adjustment of PWV to mean BP attenuated markedly both the age and the strain effects. After adjustment for body weight, either alone or associated with mean BP, the age effect was not more significant, but the strain effect was markedly enhanced. In conscious unanesthetized SHR and WKY rats, aortic stiffness is consistently associated with body weight independent of age and mean BP. An intervention study should consider in the objectives systolic BP and PP amplifications measured in conscious animals, central control of body weight, and autonomic nervous system.

Optimal frequency ranges for extracting information on cardiovascular autonomic control from the blood pressure and pulse interval spectrograms in mice.

The analysis of blood pressure (BP) and heart rate (HR) variability by spectral methods has proven a useful tool in many animal species for the assessment of the vagal and sympathetic contributions to oscillations of BP and HR. Continuous BP measurements obtained in mice by telemetry were used to characterize the spectral bandwidths of autonomic relevance by using an approach with no a priori. The paradigm was based on the autonomic blockades obtained with conventional drugs (atropine, prazosin, atenolol). The spectral changes were estimated in all of the combinations of spectral bandwidths. The effect of hydralazine was also tested using the same systematic analysis, to detect the zones of sympathetic activation resulting reflexly from the vasodilatory action of the drug. Two zones of interest in the study of the autonomic control of BP and HR were observed. The first zone covered the 0.15-0.60 Hz range of the systolic BP spectrum and corresponds to the low-frequency zone (or Mayer waves). This zone reflects sympathetic control since the power spectral density of this zone was significantly reduced with alpha1-adrenoceptor blockade (prazosin), while it was significantly amplified as a result of a reflex sympathetic activation (hydralazine). The second zone covered the 2.5-5.0 Hz range of the pulse interval spectrum and corresponded to the high-frequency zone (respiratory sinus arrhythmia) under vagal control (blocked by atropine). These zones are recommended for testing the autonomic control of circulation in mice.