Biosynthetic infochemical communication.

There is an ever-increasing demand for data to be embedded in our environment at ever-decreasing temporal and spatial scales. Whilst current communication and storage technologies generally exploit the electromagnetic properties of media, chemistry offers us a new alternative for nanoscale signaling using molecules as messengers with high information content. Biological systems effectively overcome the challenges of chemical communication using highly specific biosynthetic pathways for signal generation together with specialized protein receptors and nervous systems. Here we consider a new approach for information transmission based upon nature's quintessential example of infochemical communication, the moth pheromone system. To approach the sensitivity, specificity and versatility of infochemical communication seen in nature, we describe an array of biologically-inspired technologies for the production, transmission, detection, and processing of molecular signals. We show how it is possible to implement each step of the moth pheromone pathway for biosynthesis, transmission, receptor protein binding/transduction, and antennal lobe processing of monomolecular and multimolecular signals. For each implemented step, we discuss the value, current limitations, and challenges for the future development and integration of infochemical communication technologies. Together, these building blocks provide a starting point for future technologies that can utilize programmable emission and detection of multimolecular information for a new and robust means of communicating chemical information.

Documentation of atrial fibrillation prior to first-ever ischemic stroke.

OBJECTIVES: We assessed the prevalence of atrial fibrillation (AF) prior to first-ever ischemic stroke by examining a comprehensive electronic ECG archive. METHODS: The study sample comprised 336 consecutive stroke patients (median age 76 (IQ16) y, 200 men) enrolled in Lund Stroke Register from March 2001 to February 2002 and 336 age- and gender-matched controls without stroke history. AF prior to admission was studied using the regional electronic ECG database and record linkage with the National Swedish Hospital Discharge Register (SHDR). Medical records were reviewed for AF documentation and CHA2 DS2-VASc risk score. RESULTS: Atrial fibrillation before or at stroke onset was detected in 109 (32.4%) stroke patients and 44 (13.1%) controls, P<0.001. Twenty-five of 109 stroke patients had AF detected only on previous ECG (n=14) or through the SHDR (n=11). The most prevalent type of AF in stroke group was non-permanent AF (59.6%). AF prevalence among patients admitted with sinus rhythm at hospital admission (n=266) was higher in those with CHA2 DS2 -VASc score≥6 (28.6%) than with CHA2 DS2-VASc score<6 (13.0%), P=0.043. CONCLUSION: Comprehensive approach for AF screening allows detecting AF in one-third of patients admitted with first-ever ischemic stroke. Patients with high cardiovascular risk are more likely to have non-permanent AF.

Atrial myocardial pathoelectrophysiology in adults with a secundum atrial septal defect is unaffected by closure of the defect. A study using high resolution signal-averaged orthogonal P-wave technique.

BACKGROUND: In patients with atrial septal defect (ASD) the P-wave is prolonged as a marker of delayed atrial conduction which is associated with atrial fibrillation. The study aim was to analyse the impact of ASD closure in adults on P-wave duration and morphology by means of signal-averaged P-waves (PSA-ECG) and to investigate potential mechano-electrical interactions. METHODS: PSA-ECG was obtained before and 8+/-6 months after ASD closure in 35 adult patients (age 53+/-15 years). Heart chamber sizes and pulmonary artery pressure levels were assessed by echoDopplercardiography. RESULTS: P-wave duration and morphology did not change after ASD closure (148+/-16 vs 144+/-16 ms, P=0.07). P-wave duration did not relate to age at repair, preclosure atrial sizes or pulmonary artery pressure. Pre- or postclosure atrial fibrillation propensity was associated with longer P-wave duration both before and after ASD closure. CONCLUSION: Atrial conduction disturbances in middle-aged patients with ASD, manifested as a prolonged P-wave duration, do not change after ASD closure and are not related to the dilatation of the right and left atria. It is suggestive that atrial conduction disturbance associated with ASD develop early and early intervention is required to prevent the development of late atrial fibrillation.

Digitalis: a dangerous drug in atrial fibrillation? An analysis of the SPORTIF III and V data.

OBJECTIVE: In heart failure, digitalis increases exercise capacity and reduces morbidity, but has no effect on survival. This raises the suspicion that the inotropic benefits of digitalis may be counteracted by serious adverse effects. Patients with atrial fibrillation (AF) were studied to clarify this. DESIGN: In the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF) III and V studies, 7329 patients with AF at moderate-to-high risk were randomised to preventive treatment of thromboembolism, either with warfarin or the oral direct thrombin inhibitor ximelagatran. The survival of users and non-users of digitalis was investigated. RESULTS: At baseline, 53.4% of the study population used digitalis, and these patients had a higher mortality than non-users (255/3911 (6.5%) vs 141/3418 (4.1%), p<0.001; hazard ratio (HR) = 1.58 (95% CI 1.29 to 1.94)). Digitalis users also had more baseline risk factors. After multivariate risk factor adjustment, the increased mortality persisted (p<0.001; HR = 1.53 (95% CI 1.22 to 1.92 vs 1.23 to 1.92)). CONCLUSIONS: The results suggest that digitalis, like other inotropic drugs, may increase mortality. This may be concealed in heart failure, but be revealed in patients with AF, who need the rate-reducing effect of digitalis, but do not benefit much from an increased inotropy. Cautious interpretation of the data is mandatory since the patients were not randomised with respect to digitalis use.

Sinus rhythm maintenance following DC cardioversion of atrial fibrillation is not improved by temporary precardioversion treatment with oral verapamil.

OBJECTIVE: To evaluate prospectively the effects of pretreatment with verapamil on the maintenance of sinus rhythm after direct current (DC) cardioversion. DESIGN: Randomised, active control, open label, parallel group comparison of verapamil versus digoxin. SETTINGS: Multicentre study in three teaching and three non-teaching hospitals in Sweden. PATIENTS: 100 consecutive patients with atrial fibrillation (AF) of at least four weeks' duration and indications for cardioversion were assigned randomly to two groups, one treated with verapamil (verapamil group) and the other with digoxin (digoxin group) before cardioversion. Fifty patients were assigned randomly to each treatment arm. After dropout of four patients from the digoxin group and seven patients from the verapamil group, data obtained from 89 patients were analysed. INTERVENTIONS: After randomly assigned pretreatment with either verapamil or digoxin for four weeks, DC cardioversion was performed. If sinus rhythm was restored then verapamil treatment was discontinued. MAIN OUTCOME MEASURES: The rate of AF recurrence was assessed one, four, eight, and 12 weeks after cardioversion. RESULTS: 6 patients in the verapamil treated group and none in the digoxin treated group reverted to sinus rhythm spontaneously (p < 0.05). DC cardioversion restored sinus rhythm in 24 of 37 (65%) patients in the verapamil group and 41 of 46 patients (89%) in the digoxin group (p < 0.05). After 12 weeks' follow up 28% (13 of 46) of digoxin pretreated patients versus 9% (four of 43) of verapamil pretreated patients remained in sinus rhythm (p < 0.05). CONCLUSION: Pretreatment with verapamil alone does not improve maintenance of sinus rhythm after DC cardioversion in patients with AF. The rate of spontaneous cardioversion may be improved by verapamil.

Changes in tissue optical properties due to radio-frequency ablation of myocardium.

The optical properties of pig heart tissue were measured after in vivo ablation therapy had been performed during open-heart surgery. In vitro samples of normal and ablated tissue were subjected to measurements with an optically integrating sphere set-up in the region 470-900 nm. Three independent measurements were made: total transmittance, total reflectance and collimated transmittance, which made it possible to extract the absorption and scattering coefficients and the scattering anisotropy factor g, using an inverse Monte Carlo model. Between 470 and 700 nm, only the reduced scattering coefficient and absorption could be evaluated. The absorption spectra were fitted to known tissue chromophore spectra, so that the concentrations of haemoglobin and myoglobin could be estimated. The reduced scattering coefficient was compared with Mie computations to provide Mie equivalent average radii. Most of the absorption was from myoglobin, whereas haemoglobin absorption was negligible. Metmyoglobin was formed in the ablated tissue, which could yield a spectral signature to distinguish the ablated tissue with a simple optical probe to monitor the ablation therapy. The reduced scattering coefficient increased by, on average, 50% in the ablated tissue, which corresponded to a slight decrease in the Mie equivalent radius.

Morphology of inter-atrial conduction routes in patients with atrial fibrillation.

BACKGROUND: Inter-atrial conduction disturbance is associated with the presence of atrial fibrillation (AF), although little is known about the anatomy of the inter-atrial connections. METHODS AND RESULTS: Twenty-seven hearts from in-hospital deaths were examined and stratified in two groups with regard to their history of AF. Measurements of atrial weight were performed after excising the atria at the level of the atrioventricular valve plane and separation from the inter-atrial septum (IAS). In addition, in 15 of 27 hearts (seven AF, eight non-AF) the IAS was sliced into 10 microm thick parallel histological sections at intervals of 1 mm starting at the valve plane and ending at the atrial roof. The sections were stained with van Gieson's stain. The variable morphology of the anterior and posterior inter-atrial connective muscle bundles is described. The total number of inter-atrial connections varied from 1 to 5. The anterior route (Bachmann's bundle) was not found in seven of 15 specimens. CONCLUSION: Inter-atrial connections are characterized by substantial variability in morphology and in the distribution of bundles. This may account for part of the variable susceptibility to AF.

Dispersion of atrial repolarization in patients with paroxysmal atrial fibrillation.

UNLABELLED: To study the role of the dispersion of atrial repolarization (DAR) in the genesis of atrial fibrillation (AF), monophasic action potentials (MAP) were recorded simultaneously from a catheter at the high lateral right atrium (HLRA) and a catheter moving around the high, middle and low lateral right atrium (RA) the high, anterior and posterior septal RA and the RA appendage in 15 patients with paroxysmal AF and 15 patients with atrioventricular nodal re-entry tachycardia (AVNRT) or concealed Wolff-Parkinson-White syndrome (WPW) without history of AF. After recordings during sinus rhythm (SR), MAPs were recorded during programmed stimulation (PS) via the HLRA catheter at a drive cycle length (CL) of 500 ms. Thus, MAPs were recorded simultaneously from 2 sites at a time and sequentially from 4 to 12 sites during SR, drive pacing and PS. Taking the MAP at the HLRA as reference, the dispersion of repolarization time (dispersion of RT) and its two components, the dispersions of activation time (dispersion of AT) and MAP duration (dispersion of MAP duration) among the 4 to 12 sites were calculated and taken as parameters of DAR. RESULTS: During SR and PS, the maximal dispersion of RT was significantly greater in AF than in control patients, 113+/-49 ms vs 50+/-28 ms (P<0.001) and 114+/-56 vs 70+/-43 ms (P<0.05) respectively. The increased dispersion of RT in the AF group was caused by increases in both dispersion of MAP duration and dispersion of AT. CONCLUSION: During SR and PS, DAR increased in patients with paroxysmal AF due to increases in dispersion of MAP duration and dispersion of AT, which suggests the involvement of both repolarization and conduction disturbances in the development of paroxysmal AF.

Gender and atrioventricular conduction properties of patients with symptomatic atrioventricular nodal reentrant tachycardia and Wolff-Parkinson-White syndrome.

The objective of this study was to delineate the sex distribution and atrioventricular conduction properties in patients with manifest or concealed Wolff-Parkinson-White syndrome (WPW) and atrioventricular nodal reentrant tachycardia (AVNRT). The study comprised 328 patients with AVNRT, 347 with manifest, and 220 with concealed WPW who underwent radiofrequency ablation. A male preponderance was observed in patients with manifest WPW (69%), but not in those with concealed WPW (52%) and female preponderance in AVNRT patients (67%). The PR (166 +/- 25 ms) and AH (88 +/- 20 ms) intervals obtained 30 minutes after ablation in manifest WPW patients were significantly longer than in concealed WPW patients (149 +/- 20, 76 +/- 15 ms, P <.0001). The PR (146 +/- 20 ms) and AH intervals (75 +/- 15 ms) measured before ablation in AVNRT patients were shorter than those obtained before ablation in concealed WPW patients (154 +/- 21, 80 +/- 17 ms, P <.05) and after ablation in manifest WPW patients (P <.0001). The PR interval in AVNRT patients was also shorter than those measured during follow-up in concealed (153 +/- 21 ms, P <.05) and manifest WPW patients (165 +/- 23 ms, P <.0001). The ventriculoatrial block cycle length in AVNRT patients was significantly shorter than in manifest and concealed WPW patients. When age-matched patients were assigned to each group, significant differences in PR interval were observed between men and women (159 +/- 22 vs. 151 +/- 22 ms, P <.0001). Differences in sex distribution exist among patients with manifest and concealed WPW and AVNRT. The atrioventricular conduction properties required for the manifestation of pre-excitation and induction of AVNRT and gender differences in atrioventricular conduction may account for the differences in sex distribution.

Atrioventricular conduction: a determinant for the manifestation of ventricular preexcitation in patients with Wolff-Parkinson-White syndrome.

The relation between the atrioventricular conduction properties of the atrioventricular node and the anterograde conduction ability over the accessory pathway in the Wolff-Parkinson-White syndrome has never been studied. Atrioventricular nodal characteristics were studied in 285 patients with manifest and 204 with concealed accessory pathway who underwent radiofrequency ablation, and compared with 146 controls. First and second degree atrioventricular block was observed in 13 (5%) preexcitation patients after ablation, compared with none in concealed accessory pathway (P=0.001) and control patients (P=0.006). The atrial-His intervals in preexcitation patients (88 +/- 20 ms) was significantly longer than in concealed accessory pathway (76 +/- 15 ms, P<0.0001) and control patients (77 +/- 15 ms, P=0.0007), as was PR intervals (165 +/- 25 versus 149 +/- 20 and 150 +/- 21 ms, P<0.0001, respectively) even after excluding those with atrioventricular block. Significant differences in PR and atrial-His intervals were not observed between concealed accessory pathway and control patients. More preexcitation patients had ventriculoatrial dissociation than had patients in the other groups. The results indicate that atrioventricular block is not uncommon in preexcitation patients and a relatively long atrioventricular conduction time is an electrophysiological prerequisite for the manifestation of preexcitation in the Wolff-Parkinson-White syndrome.

Atrial fibrillation--Where do we stand today?

The basic underlying mechanisms behind atrial fibrillation (AF), the most abundant therapy demanding cardiac dysrhythmia, have until recently being largely unknown. Once established, AF is not only self-perpetuating but also self-destructive, prompting rapid treatment against possible initiating mechanisms. Recent observations reveal that the ectopic beats, initiating AF, often originate in the walls of the pulmonary veins and that the deterioration of the ectopic impulse to AF may be linked to an impaired inferoposterior interatrial conduction. The underlying mechanisms behind these functional defects are still obscure. The observations has however, permitted evaluation of new types of treatment, directly interfering with the newly verified findings.

An unusual cause of tachycardiomyopathy: incessant atypical AV nodal reentrant tachycardia induced by 1:2 AV conduction.

We report a 62-year-old female with cardiomyopathy mediated by incessant atypical atrioventricular nodal reentrant tachycardia, which was induced by 1:2 atrioventricular conduction. Her arrhythmia was identified and cured by radiofrequency catheter ablation. Follow-up over the course of next 5 months the patient's cardiomyopathy dramatically improved.

Further evidence of localized posterior interatrial conduction delay in lone paroxysmal atrial fibrillation.

AIMS: Prolongation of interatrial conduction time has been reported in patients with paroxysmal atrial fibrillation (PAF). The study objective was to localize the region of the conduction delay in patients with lone PAF. METHODS AND RESULTS: Twenty-one patients with lone PAF and 23 patients with AV nodal re-entrant tachycardia ablation without history of PAF (control group) were recruited. Endocardial recordings were made during sinus rhythm and programmed atrial stimulation. The authors measured the interatrial conduction time, the 'right-sided' conduction time between the high lateral right atrium and the proximal coronary sinus (RA-CSp), and the 'left-sided' conduction time between the proximal and the distal coronary sinus (CSp-LA). During sinus rhythm, the interatrial conduction time was longer in the PAF group (103 +/- 19 vs 86 +/- 12 ms, P<0.01) due to delay of right-sided conduction (RA-CSp was 74 +/- 20 vs 56 +/- 10 ms, P<0.01). During programmed stimulation at the distal coronary sinus, the maximal RA-CSp time was also longer in the PAF group (110 +/- 47 vs 69 +/- 16 ms, P<0.05). No differences in CSp-LA time were observed. CONCLUSION: This study supports the role of posterior septal right atrial conduction disturbances in the genesis of lone PAF.

Classification of electrocardiographic P-wave morphology.

The atrial activity of the human heart is normally visible in the electrocardiogram as a P-wave. In patients with intermittent atrial fibrillation, a different P-wave morphology can sometimes be seen, indicating atrial conduction defects. The purpose of this study was to develop a method to discriminate between such P-waves and normal ones. 20 recordings of each type were used in a classification which, based on impulse response analysis of the P-wave and linear discrimination between various parameters, produced a correct classification in 37 of the 40 recordings (sensitivity 95%, specificity 90%).

Characterization of atrial fibrillation using the surface ECG: time-dependent spectral properties.

Time-frequency analysis is considered for characterizing atrial fibrillation in the surface electrocardiogram (ECG). Variations in fundamental frequency of the fibrillatory waves are tracked by using different time-frequency distributions which are appropriate to short- and long-term variations. The cross Wigner-Ville distribution is found to be particularly useful for short-term analysis due to its ability to handle poor signal-to-noise ratios. In patients with chronic atrial fibrillation, substantial short-term variations exist in fibrillation frequency and variations up to 2.5 Hz can be observed within a few seconds. Although time-frequency analysis is performed independently in each lead, short-term variations in fibrillation frequency often exhibit a similar pattern in the leads V1, V2 and V3. Using different techniques for short- and long-term analysis, it is possible to reliably detect subtle long-term changes in fibrillation frequency, e.g., related to an intervention, which otherwise would have been obscured by spontaneous variations in fibrillation frequency.

Diurnal variations of the dominant cycle length of chronic atrial fibrillation.

High-resolution digital Holter recording was carried out in 21 patients (15 men, 64 +/- 12 yr) with chronic atrial fibrillation. Dominating atrial cycle length (DACL) was derived by frequency domain analysis of QRST-reduced electrocardiograms. Daytime mean DACL was 150 +/- 17 ms, and nighttime mean was 157 +/- 22 ms (P = 0. 0002). Diurnal fluctuation in DACL differed among patients: it tended to be virtually absent in those with a short mean DACL, but in those with longer DACL the night-day difference was as much as 23 ms (R = 0.72, P < 0.001, correlation of mean DACL to night-day difference). Mean DACL also correlated with ventricular cycle length (R = 0.40, P < 0.001), particularly at night (r = 0.49). The shorter cycle lengths found in this study during the day are consistent with sympathetic and/or other physiological modulation, but since increased vagal tone shortens atrial refractoriness in most models, parasympathetic influences are not likely to play a major role. Alternatively, atrial effective refractory period may not be the sole determinant of atrial cycle length during atrial fibrillation.

Non-invasive assessment of atrial fibrillation (AF) cycle length in man: potential application for studying AF.

Non-invasive assessment of the fibrillatory frequency of atrial fibrillation (AF) can be performed by frequency domain analysis. The peak frequency in the derived spectrum can be converted to a dominant atrial cycle length (DACL). The DACL can be altered through autonomic modulation or pharmacologic manipulation, but the change in DACL is less marked in those with a short DACL value. In patients with AF, those with a short duration of the arrhythmia have longer DACL values. Finally, patients with paroxysmal AF generally exhibit longer DACL values than patients with permanent AF. Thus non-invasive assessment of the atrial fibrillatory cycle length provides a useful index of atrial refractoriness and has the potential of clinical utility in patient assessment and treatment planning.

Localization of the initial fibrillatory cycle in patients with paroxysmal atrial fibrillation.

BACKGROUND: Recent reports suggest the presence of conduction delay in the posterior septal region during sinus rhythm in patients with lone paroxysmal atrial fibrillation (AF). OBJECTIVE: To explore the location of intra-atrial conduction delay associated with initiation of AF. DESIGN: In 8 lone AF patients (51 +/- 10 years), 20 AF paroxysms were induced during electrophysiological examination. Bipolar electrograms were acquired from a 10-polar catheter in the coronary sinus (CS), a 4-polar His bundle catheter, and a 20-polar Halo catheter in the right atrium. RESULTS: Induced AF paroxysms showed earliest registered atrial activity in interatrial septum (IAS) or proximal CS in 17 cases (85%). Conduction delay at the posterior IAS or proximal CS accompanied induction of 18 AF paroxysms (6 patients). Atrial activation sequence at the beginning of the AF paroxysms was stable and reproducible in six repeatedly induced AF episodes (3 patients). CONCLUSION: In lone AF patients, induction of AF is associated with conduction disturbances in the IAS and proximal CS regions.

Gender differences in the electrophysiological characteristics of atrioventricular conduction system and their clinical implications.

OBJECTIVE: The underlying mechanisms of the differences in sex distribution of patients with atrioventricular (AV) nodal re-entrant tachycardia and Wolff-Parkinson-White syndrome are poorly understood. The objective of this study was to determine potential gender differences in the electrophysiological properties of the normal AV conduction system that may be attributable to differences in sex distribution. DESIGN: The AV conduction properties were studied in 96 patients (52 men and 44 women) who underwent electrophysiological testing, 32 patients with atrial tachycardia, 39 with idiopathic ventricular tachycardia and 25 with unexplained palpitations or syncope. RESULTS: The AH (83 +/- 15 ms) and His-ventricular intervals in men (42 +/- 6 ms) were significantly longer than in women (78 +/- 14, 38 +/- 6 ms, p < 0.05, respectively), as was the PR interval (160 +/- 17 vs 152 +/- 13 ms, p = 0.02). The effective refractory period of AV node in men (349 +/- 75 ms) was longer than in women (297 +/- 45 ms, p = 0.03). However, no significant difference was observed between men and women with respect to the incidence of AV nodal dual pathway and the maximum AH interval achieved during premature stimulation or incremental pacing. The AV block cycle length was significantly longer in men (371 +/- 76 ms) than in women (330 +/- 52 ms, p = 0.02). A longer ventriculoatrial block cycle length was also found in men than in women although not at a significant level (436 +/- 107 vs 384 +/- 90 ms. p = 0.08). In addition, men (23%) were twice as likely to have ventriculoatrial dissociation during ventricular pacing as women were (11%, p = 0.2). CONCLUSION: The data show that gender-related differences in AV conduction properties may be responsible for the differences in sex distribution observed in patients with AV nodal re-entrant tachycardia and those with ventricular pre-excitation.

Effects of MgSO4 and glucose, insulin and potassium (GIK) on atrial conduction during the first 12 hours after DC-conversion of chronic atrial fibrillation.

OBJECTIVE: To investigate changes in atrial conduction induced by MgSO4 and glucose, insulin and potassium (GIK) during the first 12-h period of sinus rhythm after successful DC-conversion of chronic atrial fibrillation (CAF). METHODS: Signal-averaged P-wave duration, QRS-duration and PQ-time were recorded in 20 patients who were randomly assigned to control or intervention. Ten patients received no infusates (control group) and 10 patients received MgSO4 and GIK infusions (intervention group). P-wave duration was determined from the X-, Y- and Z-leads, which were further combined to obtain a spatial magnitude. P-wave morphology was studied by analysing global activation patterns and discrete components from the calculated spatial magnitude signal. RESULTS: No changes in the measured parameters were seen in the control group. The P-wave duration, QRS-duration and PQ-time increased from 139(13) [mean(SD)] to 149(15) (p < 0.01), 90(7) to 94(9) (p < 0.05) and 188(10) to 207(13) ms (p < 0.01). respectively, after bolus infusion of MgSO4. The time from the start of the P-wave to its 1st and 2nd max. locations increased by 6 ms (p < 0.01) in both cases after bolus infusion of MgSO4 and had reversed after 10 h of MgSO4 and GIK infusion. P-wave duration and PQ-time decreased after 10 h of MgSO4 and GIK infusion, from 149(34) (bolus) to 138(12) and from 207(13) to 195(27) ms (p < 0.05), respectively, in spite of an even higher serum Mg concentration at the end of this period. CONCLUSION: Bolus infusion of MgSO4 2 h after DC-conversion of CAF produced an intra-atrial conduction delay that could be reversed by adding a GIK infusion, in spite of a concomitant increase in serum Mg concentration. No recovery of the intra-atrial conduction delay, seen after DC-conversion of CAF, was observed in either of the two groups during the 12-h study period.