Two alpha1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation.

To study the functional role of individual alpha1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha1B-AR and/or alpha1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha1D-AR knockout and alpha1B-/alpha1D-AR double knockout mice, but not the alpha1B-AR knockout mice, had significantly (p < 0.05) lower levels of basal systolic and mean arterial BP than wild-type mice in nonanesthetized condition, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. All mutants showed a significantly (p < 0.05) reduced catecholamine-induced pressor and vasoconstriction responses. It is noteworthy that the infusion of norepinephrine did not elicit any pressor response at all in alpha1B-/alpha1D-AR double knockout mice. In an attempt to further examine alpha1-AR subtype, which is involved in the genesis or maintenance of hypertension, BP after salt loading was monitored by tail-cuff readings and confirmed at the endpoint by direct intra-arterial recording. After salt loading, alpha1B-AR knockout mice developed a comparable level of hypertension to wild-type mice, whereas mice lacking alpha1D-AR had significantly (p < 0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that alpha1B- and alpha1D-AR subtypes participate cooperatively in BP regulation; however, the deletion of the functional alpha1D-AR, not alpha1B-AR, leads to an antihypertensive effect. The study shows differential contributions of alpha1B- and alpha1D-ARs in BP regulation.

Disparate activation of the coronary sinus and inferior left atrium during atrial tachycardia after persistent atrial fibrillation ablation: prevalence, pitfalls, and impact on mapping.

INTRODUCTION: Persistent atrial fibrillation (AF) ablation may lead to partial disconnection of the coronary sinus (CS). As a result, disparate activation sequences of the local CS versus contiguous left atrium (LA) may be observed during atrial tachycardia (AT). We aimed to evaluate the prevalence of this phenomenon and its impact on activation mapping. METHODS: AT occurring after persistent AF ablation were investigated in 74 consecutive patients. Partial CS disconnection during AT was suspected when double potentials with disparate activation sequences were observed on the CS catheter. Endocardial mapping facing CS bipoles was performed to differentiate LA far-field from local CS potentials. RESULTS: A total of 149 ATs were observed. Disparate LA-CS activations were apparent in 20 ATs after magnifying the recording scale (13%). The most common pattern (90%) was distal to proximal endocardial LA activation against proximal to distal CS activation, the latter involving the whole CS or its distal part. Perimitral macroreentry was more common when disparate LA-CS activations were observed (67% vs 29%; P = 0.002). Partial CS disconnection also resulted in "pseudo" mitral isthmus (MI) block during LA appendage pacing in 20% of patients as local CS activation was proximal to distal despite distal to proximal activation of the contiguous LA. CONCLUSION: Careful analysis of CS recordings during AT following persistent AF ablation often reveals disparate patterns of activation. Recognizing when endocardial LA activation occurs in the opposite direction to the more obvious local CS signals is critical to avoid misleading interpretations during mapping of AT and evaluation of MI block.

Dissociation of allocentric and egocentric orientation: Effect on hippocampal place cells and place navigation

Navigation by means of cognitive maps appears to require the hippocampus; hippocampal place cells (PCs) appear to store spatial memories because their discharge is confined to cell-specific places called firing fields (FFs). Experiments with rats manipulated idiothetic and landmark-related information to understand the relationship between PC activity and spatial rotation. Rotating a circular arena in the caused a discrepancy between these cuse. This discrepancy caused most FFs to disappear in both the arena and room reference frames. However, FFs persisted in the rotating arena frame when the discrepancy was reduced by darkness or by a card in the arena. The discrepancy was increased by "field clamping" the rat in a room-defined FF location by rotations that countered its locomotion. Most FFs disspared and reappeared an hour or more after the clamp. Place-avoidance experiments showed that navigation uses independent idiothetic and exteroceptive memories. Rats learned to avoid the unmarked footshock region within a circular arena. When acquired on the stable arena in the light, the location of the punishment was learned by using both room and idiothetic cues; extinction in the dark transferred to the following session in the light. If, however, extinction occured during rotation, only the arena-frame avoidance was extinguished in darkness; the room-defined location was avoided when the light were turned back on. Idiothetic memory of room-defined avoidance was not formed during rotation in light; regardless of rotation with a randomly dispersed pellet. The resulting behaviour alternated between random pellet searching and target-directed navigation, making it possible to examine PC correlates of these two classes of spatial behaviour. The independence of idiothetic and exteroceptive spatial memories and the disruption of PC firing during rotation suggest that PCs may not be necessary for spatial cognition; this idea can be tested by recording during place-avoidance and preference tasks.

Non-invasive dry mass determination and monitoring at the single cell level with digital holographic microscopy

Digital holography microscopy (DHM) is an optical microscopy technique which allows recording non-invasively the phase shift induced by living cells with nanometric sensitivity. Here, we exploit the phase signal as an indicator of dry mass (related to the protein concentration). This parameter allows monitoring the protein production rate and its evolution during the cell cycle. ©2008 COPYRIGHT SPIE

Electroencephalogram changes during inhalation with nitric oxide in the pediatric intensive care patient--a preliminary report.

OBJECTIVES: Although endogenous nitric oxide (NO) is an excitatory mediator in the central nervous system, inhaled NO is not considered to cause neurologic side effects because of its short half-life. This study was motivated by a recent case report about neurologic symptoms and our own observation of severe electroencephalogram (EEG) abnormalities during NO inhalation. DESIGN: Blind, retrospective analyses of EEGs which were registered before, during, and after NO inhalation. EEG was classified in a 5-point rating system by an independent electroencephalographer who was blinded to the patients' clinical histories. Comparisons were made with the previous evaluation documented at recording. Other EEG-influencing parameters such as oxygen saturation, hemodynamics, electrolytes, and pH were evaluated. SETTING: Pediatric intensive care unit of a tertiary care university children's hospital. PATIENTS: Eleven ventilated, long-term paralyzed, sedated children (1 mo to 14 yrs) who had EEG or clinical assessment before NO treatment and EEG during NO inhalation. They were divided into two groups according to the NO-indication (e.g., congenital heart defect, acute respiratory distress syndrome). MEASUREMENTS AND MAIN RESULTS: All 11 patients had an abnormal EEG during NO inhalation. EEG-controls without NO showed remarkable improvement. EEG abnormalities were background slowing, low voltage, suppression burst (n = 2), and sharp waves (n = 2) independent of patients' age, NO-indication, and other EEG-influencing parameters. CONCLUSIONS: These preliminary data suggest the occurrence of EEG-abnormalities after application of inhaled NO in critically ill children. We found no correlation with other potential EEG-influencing parameters, although clinical state, medication, or hypoxemia might contribute. Comprehensive, prospective, clinical assessment regarding a causal relationship between NO-inhalation and EEG-abnormalities and their clinical importance is needed.

The return of increased blood pressure after discontinuation of antihypertensive treatment is associated with an impaired post-ischemic skin blood flow response.

OBJECTIVE: To assess the post-ischemic skin blood flow response after withdrawal of antihypertensive therapy in hypertensive patients with normal blood pressure during treatment. DESIGN AND METHODS: Twenty hypertensive patients (group A) with a normal clinic blood pressure (<140/ 90 mmHg) receiving antihypertensive treatment (any monotherapy; one pill per day for at least 6 months) had their treatment discontinued. Before medication withdrawal and 2, 4, 12 and 24 weeks thereafter, the following measurements were made: clinic blood pressure, home blood pressure (three times per week, morning and evening) and skin blood flow response to a 5 min forearm arterial occlusion (using laser Doppler flowmetry). The patients were asked to perform an ambulatory blood pressure recording at any time if home blood pressure was > or =160/95 mmHg on two consecutive days, and treatment was initiated again, after determination of the skin hyperemic response, if daytime ambulatory blood pressure was > or =140/90 mmHg. The same studies were performed in 20 additional hypertensive individuals in whom antihypertensive treatment was not withdrawn (group B). The allocation of patients to groups A and B was random. RESULTS: The data fom 18 patients in group A who adhered strictly to the procedure were available for analysis. Seven of them had to start treatment again within the first 4 weeks of follow-up; four additional patients started treatment again during the next 8 weeks (group A1). The seven other patients remained untreated (group A2). The skin hyperemic response decreased significantly in patients in group A1 and returned to baseline values at the end of the study, when there were again receiving antihypertensive treatment. In patients in group A2 a significant attenuation of the hyperemic response was also observed. This impaired response was present even at the end of the 6 month follow-up, at which time the patients were still untreated but exhibited a significantly greater blood pressure than before drug discontinuation. The hyperemic response of patients who did not stop treatment (group B) did not change during the course of the study. CONCLUSIONS: Our findings show a decrease in the postischemic skin blood flow response after withdrawal of antihypertensive treatment in hypertensive patients. This impaired response may be due to the development of endothelial dysfunction, vascular remodeling, or both, and might contribute to the return of blood pressure to hypertensive values after withdrawal of antihypertensive therapy.

Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study.

BACKGROUND: Sleep-disordered breathing is associated with major morbidity and mortality. However, its prevalence has mainly been selectively studied in populations at risk for sleep-disordered breathing or cardiovascular diseases. Taking into account improvements in recording techniques and new criteria used to define respiratory events, we aimed to assess the prevalence of sleep-disordered breathing and associated clinical features in a large population-based sample. METHODS: Between Sept 1, 2009, and June 30, 2013, we did a population-based study (HypnoLaus) in Lausanne, Switzerland. We invited a cohort of 3043 consecutive participants of the CoLaus/PsyCoLaus study to take part. Polysomnography data from 2121 people were included in the final analysis. 1024 (48%) participants were men, with a median age of 57 years (IQR 49-68, range 40-85) and mean body-mass index (BMI) of 25·6 kg/m(2) (SD 4·1). Participants underwent complete polysomnographic recordings at home and had extensive phenotyping for diabetes, hypertension, metabolic syndrome, and depression. The primary outcome was prevalence of sleep-disordered breathing, assessed by the apnoea-hypopnoea index. FINDINGS: The median apnoea-hypopnoea index was 6·9 events per h (IQR 2·7-14·1) in women and 14·9 per h (7·2-27·1) in men. The prevalence of moderate-to-severe sleep-disordered breathing (≥15 events per h) was 23·4% (95% CI 20·9-26·0) in women and 49·7% (46·6-52·8) in men. After multivariable adjustment, the upper quartile for the apnoea-hypopnoea index (>20·6 events per h) was associated independently with the presence of hypertension (odds ratio 1·60, 95% CI 1·14-2·26; p=0·0292 for trend across severity quartiles), diabetes (2·00, 1·05-3·99; p=0·0467), metabolic syndrome (2·80, 1·86-4·29; p<0·0001), and depression (1·92, 1·01-3·64; p=0·0292). INTERPRETATION: The high prevalence of sleep-disordered breathing recorded in our population-based sample might be attributable to the increased sensitivity of current recording techniques and scoring criteria. These results suggest that sleep-disordered breathing is highly prevalent, with important public health outcomes, and that the definition of the disorder should be revised. FUNDING: Faculty of Biology and Medicine of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, Ligue Pulmonaire Vaudoise.

Etude de la torpeur chez Suncus etruscus (Savi, 1822) (Soricidae, Insectivora) en captivité

Some aspects of torpor have been studied among captive Suncus etruscus by recording the nest temperature. Torpors show a circadian pattern and occur spontaneously or can be induced by food shortage. Body temperature can be controlled during torpor, remaining relatively high at low ambiant temperatures. At 20° C, spontaneous torpors seem to be less deep than induced tropors, but both show similar patterns at 5-8 ° C. Spontaneous torpors begin between 01°° and 06°°, whereas the onset of diet induced torpors seems to depend also on food exhausting. The rates of activity (A) and of torpor (T) show under constant conditions a daily variability. Increase of T is linked with a decrease of A and the relationship could agree with A(%) = Ao( 1-T/100), where Ao is daily rate of activity when T = 0. Occurence of torpor among other Soricidae, possible occurence among free living Suncus etruscus and energy saving are discussed

Regulation of the cardiac voltage-gated sodium channel Nav1.5 : regulation of Nav1.5 by ubiquitin-protein ligases of the Nedd4/Nedd4-like family and characterisation of two novel mutations in the gene encoding Nav1.5 (SCN5A) implicated in the Brugada syndrome triggered by fever

Abstract: The genesis of the cardiac action potential, which accounts for the cardiac contraction, is due to the sodium current INa mediated by the voltage-gated sodium channel Nav1.5. Several cardiac arrhythmias such as the Brugada syndrome are known te be caused by mutations in SCN5A, the gene encoding Nav1.5. Studies of these mutations allowed a better understanding of biophysical and functional properties of Nav1.5. However, only few investigations have been performed in order to understand the regulation of Nav1.5. During my thesis, I investigated different mechanisms of regulation of Nav1.5 using a heterologous expression system, HEK293 cells, coupled with a technique of sodium current recording: the patch clamp in whole cell configuration. In previous studies it has been shown that an enzyme of the Nedd4 family (Nedd4-2) regulates an epithelial sodium channel via the interaction with PY-motifs present in the latter. Interestingly, Nav1.5 contains a similar PY-motif, which motivated us to study the role of Nedd4-2 expressed in heart for the regulation of Nav1.5. In a second study, we investigated the implication of two Nav1.5 mutants, which were either less functional or net functional (Nav1.5 R535X and Nav1.5 L325R respectively) implied in the genesis of the Brugada syndrome by fever. Our results established two mechanisms implied in Nav1.5 regulation. The first one implies that following the interaction between the PY-motif of Nav1.5 and Nedd4- 2 Nav1.5 is ubiquitinated by Nedd4-2. This ubiquitination leads to the internalization of Nav1 .5. The second mechanism is a phenomenon called the "dominant negative" effect of Nav1.5 L325R on Nay1.5 where the decrease of 'Na is potentially due to the retention of Nav1.5 by Nav1.5 L325R in an undefined intracellular compartment. These studies defined two mechanisms of Nav1.5 regulation, which could play an important role for the genesis of cardiac arrhythmias where molecular processes are still poorly understood. Résumé La genèse du potentiel d'action cardiaque, permettant la contraction cardiaque, est due au courant sodique INa issu des canaux sodiques cardiaques dépendants du voltage Nav1.5. Nombreuses arythmies cardiaques telles que le syndrome de Brugada sont connues pour être liées à des mutations du gène SCN5A, codant pour Nav1.5. L'étude de ces mutations a permis une meilleure compréhension des propriétés structurelles et fonctionnelles de Nav1.5 et leurs implications dans la genèse de ces pathologies. Néanmoins peu d'études ont été menées afin de comprendre les mécanismes de régulation de Nav1.5. Mon travail de thèse a consisté à étudier des mécanismes de régulation de Nav1.5 en utilisant un système d'expression hétérologue, les cellules HEK293, couplé à une technique d'enregistrement des courants sodiques, le "patch clamp" en configuration cellule entière. La présence sur Nav1.5 d'un motif-PY similaire à ceux nécessaires pour la régulation d'un canal épithélial sodique par une enzyme de la famille de Nedd4, nous a amenée à étudier le rôle de ces ubiquitine-ligases, en particulier Nedd4-2, dans la régulation de Nav1.5. La seconde étude s'est intéressée aux conséquences de deux mutations de SCN5A codant pour deux mutants peu ou pas fonctionnels (Nav1.5 L325R et Nav1.5 R535X respectivement) retrouvées chez des patients présentant un syndrome de Brugada exacerbé par un état fébrile. Nos résultats ont permis d'établir deux mécanismes de régulation de Nav1.5 L'un par Nedd4-2 qui implique rubiquitination de Nav1.5 par cette ligase suite à l'interaction entre le motif-PY de Nav1.5 et Nedd4-2. Cette modification déclenche l'internalisation du canal impliquée dans la diminution d'INa. Le second mécanisme quant à lui est un effet "dominant négatif" de Nav1.5 L325R sur Nav1.5 aboutissant à une diminution d'INa suite à la séquestration intracellulaire potentielle de Nav1.5 par Nav1.5 L325R. Ces études ont mis en évidence deux mécanismes de régulation de Nav1.5 pouvant jouer un rôle majeur dans la genèse et/ou l'accentuation des arythmies cardiaques dont les processus moléculaires au sein des cardiomyocytes, impliquant des modifications du courant sodiques, sont encore mal compris. Résumé destiné à un large public La dépolarisation électrique de la membrane des cellules cardiaques permet la contraction du coeur. La génèse de cette activité électrique est due au courant sodique issu d'un type de canal à sodium situé dans la membrane des cellules cardiaques. De nombreuses pathologies provoquant des troubles du rythme cardiaque sont issues de mutations du gène qui code pour ce canal à sodium. Ces canaux mutants, entrainant diverses pathologies cardiaques telles que le syndrome de Brugada, ont été largement étudiées. Néanmoins, peu de travaux ont été réalisés sur les mécanismes de régulation de ce canal à sodium non muté. Mon travail de thèse a consisté à étudier certains des mécanismes de régulation de ce canal à sodium en utilisant une technique permettant l'enregistrement des courants sodiques issus de l'expression de ces canaux à sodium à la membrane de cellules mammifères. La présence sur ce canal à sodium d'une structure spécifique, similaire à celle nécessaire pour la régulation d'un canal épithélial à sodium par une enzyme appelée Nedd4-2, nous a amenée à étudier le rôle de cette enzyme dans la régulation de ce canal à sodium. La seconde étude s'est intéressée aux rôles de deux mutations du gène codant pour ce canal à sodium retrouvées chez des patients présentant un syndrome de Brugada exacerbé par la fièvre. Nos résultats nous ont permis d'établir deux mécanismes de régulation de ce canal à sodium diminuant le courant sodique l'un par l'action de l'enzyme Nedd4-2, suite à son interaction avec ce canal, qui modifie ce canal à sodium (ubiquitination) diminuant de ce fait la densité membranaire du canal. L'autre par un mécanisme suggérant un effet négatif de l'un des canaux mutants sur l'expression à la membrane du canal à sodium non muté. Ces études ont mis en évidence deux mécanismes de régulation de ce canal à sodium pouvant jouer un rôle majeur dans la genèse et/ou l'accentuation des troubles du rythme cardiaques dont les mécanismes cellulaires sont encore incompris.

Simultaneous EEG-fMRI at ultra-high field: Artifact prevention and safety assessment.

The simultaneous recording of scalp electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can provide unique insights into the dynamics of human brain function, and the increased functional sensitivity offered by ultra-high field fMRI opens exciting perspectives for the future of this multimodal approach. However, simultaneous recordings are susceptible to various types of artifacts, many of which scale with magnetic field strength and can seriously compromise both EEG and fMRI data quality in recordings above 3T. The aim of the present study was to implement and characterize an optimized setup for simultaneous EEG-fMRI in humans at 7T. The effects of EEG cable length and geometry for signal transmission between the cap and amplifiers were assessed in a phantom model, with specific attention to noise contributions from the MR scanner coldheads. Cable shortening (down to 12cm from cap to amplifiers) and bundling effectively reduced environment noise by up to 84% in average power and 91% in inter-channel power variability. Subject safety was assessed and confirmed via numerical simulations of RF power distribution and temperature measurements on a phantom model, building on the limited existing literature at ultra-high field. MRI data degradation effects due to the EEG system were characterized via B0 and B1(+) field mapping on a human volunteer, demonstrating important, although not prohibitive, B1 disruption effects. With the optimized setup, simultaneous EEG-fMRI acquisitions were performed on 5 healthy volunteers undergoing two visual paradigms: an eyes-open/eyes-closed task, and a visual evoked potential (VEP) paradigm using reversing-checkerboard stimulation. EEG data exhibited clear occipital alpha modulation and average VEPs, respectively, with concomitant BOLD signal changes. On a single-trial level, alpha power variations could be observed with relative confidence on all trials; VEP detection was more limited, although statistically significant responses could be detected in more than 50% of trials for every subject. Overall, we conclude that the proposed setup is well suited for simultaneous EEG-fMRI at 7T.

Motor overactivity and loss of motor circadian rhythm in fatal familial insomnia: an actigraphic study.

The 24-hour rest-activity pattern and the amount of motor activity was studied in a patient with fatal familial insomnia (FFI) by means of wrist actigraphy. During the study, the patient underwent indirect calorimetry. The 52-day recording showed severe disruption of the 24-hour rest-activity pattern with increased motor activity up to 80%. The 24-hour energy expenditure, assayed in a respiration chamber, was strikingly elevated by 60%. Chronic motor overactivity and loss of circadian rest-activity rhythm may play a role in the progressive metabolic exhaustion leading to death in FFI patients.

Inactivation of L-type calcium channels is determined by the length of the N terminus of mutant beta(1) subunits.

Voltage-dependent calcium channel (Ca(v)) pores are modulated by cytosolic beta subunits. Four beta-subunit genes and their splice variants offer a wide structural array for tissue- or disease-specific biophysical gating phenotypes. For instance, the length of the N terminus of beta(2) subunits has major effects on activation and inactivation rates. We tested whether a similar mechanism principally operates in a beta(1) subunit. Wild-type beta(1a) subunit (N terminus length 60 aa) and its newly generated N-terminal deletion mutants (51, 27 and 18 aa) were examined within recombinant L-type calcium channel complexes (Ca(v)1.2 and alpha(2)delta2) in HEK293 cells at the whole-cell and single-channel level. Whole-cell currents were enhanced by co-transfection of the full-length beta(1a) subunit and by all truncated constructs. Voltage dependence of steady-state activation and inactivation did not depend on N terminus length, but inactivation rate was diminished by N terminus truncation. This was confirmed at the single-channel level, using ensemble average currents. Additionally, gating properties were estimated by Markov modeling. In confirmation of the descriptive analysis, inactivation rate, but none of the other transition rates, was reduced by shortening of the beta(1a) subunit N terminus. Our study shows that the length-dependent mechanism of modulating inactivation kinetics of beta(2) calcium channel subunits can be confirmed and extended to the beta(1) calcium channel subunit.

Progression of auditory discrimination based on neural decoding predicts awakening from coma.

Auditory evoked potentials are informative of intact cortical functions of comatose patients. The integrity of auditory functions evaluated using mismatch negativity paradigms has been associated with their chances of survival. However, because auditory discrimination is assessed at various delays after coma onset, it is still unclear whether this impairment depends on the time of the recording. We hypothesized that impairment in auditory discrimination capabilities is indicative of coma progression, rather than of the comatose state itself and that rudimentary auditory discrimination remains intact during acute stages of coma. We studied 30 post-anoxic comatose patients resuscitated from cardiac arrest and five healthy, age-matched controls. Using a mismatch negativity paradigm, we performed two electroencephalography recordings with a standard 19-channel clinical montage: the first within 24 h after coma onset and under mild therapeutic hypothermia, and the second after 1 day and under normothermic conditions. We analysed electroencephalography responses based on a multivariate decoding algorithm that automatically quantifies neural discrimination at the single patient level. Results showed high average decoding accuracy in discriminating sounds both for control subjects and comatose patients. Importantly, accurate decoding was largely independent of patients' chance of survival. However, the progression of auditory discrimination between the first and second recordings was informative of a patient's chance of survival. A deterioration of auditory discrimination was observed in all non-survivors (equivalent to 100% positive predictive value for survivors). We show, for the first time, evidence of intact auditory processing even in comatose patients who do not survive and that progression of sound discrimination over time is informative of a patient's chance of survival. Tracking auditory discrimination in comatose patients could provide new insight to the chance of awakening in a quantitative and automatic fashion during early stages of coma.

Endothelial dependant coronary vasoreactivity measured by 82Rb cardiac PET in obstructive sleep apnea patients before and after CPAP treatment

Introduction: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular diseases. Endothelial dysfunction is believed to be one of the pathophysiological mechanism underlying this association. Our aim was to compare endothelial dependent coronary vasoreactivity in obstructive sleep apnea (OSA) patients and controls by quantifying myocardial blood flow (MBF) response to cold pressure testing (CPT) with 82Rb cardiac PET/CT. Methods: Twenty-four OSA patients (2W/22M, mean age 58 yo, mean BMI 28.6 kg/m2) with an apnea-hypopnea index (AHI) >30/h and 9 healthy volunteers (AHI <10/h) underwent a full night sleep recording (PSG) and a dynamic 82 Rb cardiac PET/CT scan at rest, during CPT and adenosine stress. In OSA patients the same measurements (PSG and PET/CT) were respeated 6 weeks after initiating continuous positive airway pressure (autoCPAP) treatment. To reflect differences in baseline cardiac work, values were normalized according to ratepressure product (RPP). Results: At baseline, untreated OSA patients had a mean AHI of 48.8/h and showed a lower MBF response to CPT than controls (1.1 ± 0.2 mL/min/g vs. 1.3 ± 0.4 mL/min/g, P = 0.048). When treated with CPAP, CPT-MBF was not different between controls and well-treated OSA patients (1.2 ± 0.3 mL/min/g vs 1.3 ± 0.4 mL/min/g, P = 0.68), but it was significantly lower for insufficiently treated patients (n = 10) with a residual AHI >10/h (0.9 ± 0.2 mL/min/g vs 1.3 ± 0.4 mL/min/g, P = 0.03). There was also a trend toward a difference in CPT-MBF between insufficiently and well-treated OSA patients (1.2 ± 0.3 mL/min/g vs 0.9 ± 0.2 mL/min/g, P = 0.15). Conclusion: Untreated OSA patients have an impaired coronary endothelial function as measured by MBF response to CPT compared to control subjects. This difference disappears after 6 weeks of autoCPAP therapy but only in OSA patients showing a good response to CPAP (AHI <10/h). Further studies are needed to determine by which mechanism OSA and CPAP treatment influence coronary vasoreactivity.

Mirror image atrial dilatation in adult patients with atrial fibrillation and congenital heart disease.

BACKGROUND: Atrial fibrillation (AF) is largely regarded to be initiated from left atrial (LA) dilatation, with subsequent dilatation of the right atrium (RA) in those who progress to chronic AF. We hypothesized that in adult patients with right-sided congenital heart disease (CHD) and AF, RA dilatation will predominate with subsequent dilatation of the left atrium, as a mirror image. METHODS: Adult patients with diagnosis of right-sided, ASD or left-sided CHD who had undergone an echocardiographic study and electrocardiographic recording in 2007 were included. RA and LA area were measured from the apical view. AF was diagnosed from a 12-lead electrocardiogram or Holter recording. A multivariate logistic regression model was used to identify predictors of AF and linear regression models were performed to measure relationship between RA and LA area and AF. RESULTS: A total of 291 patients were included in the study. Multivariate analysis showed that age (p=0.0001), RA (p=0.025) and LA area (p=0.0016) were significantly related to AF. In patients with pure left-sided pathologies, there was progressive and predominant LA dilatation that paralleled the development of AF from none to paroxysmal to chronic AF. In patients with pure right-sided pathologies, there was a mirror image of progressive and predominant RA dilatation with the development of AF. CONCLUSION: We observed a mirror image atrial dilatation in patients with right sided disease and AF. This may provide novel mechanistic insight as to the origin of AF in these patients and deserves further studying in the form of targeted electrophysiological studies.