bluuebunny/crossref_metadata_2025 huggingface dataset:
α2‐Adrenoreceptor activation inhibits LTP and LTD in the basolateral amygdala: involvement of Gi/o‐protein‐mediated modulation of Ca2+‐channels and inwardly rectifying K+‐channels in LTD
Authors: DeBock F. , Kurz J. , Azad S. C. , Parsons C. G. , Hapfelmeier G. , Zieglgänsberger W. , Rammes G.
Published: May 2003

Activation of adrenoreceptors modulates synaptic transmission in the basolateral amygdala. Here, we investigated the effects of α2‐adrenoreceptor activation on long‐term depression and long‐term potentiation in an in vitro slice preparation of the mouse basolateral amygdala. Field potentials and excitatory postsynaptic currents were evoked in the basolateral amygdala by stimulating the lateral amygdala. Norepinephrine (20 µm) reduced synaptic transmission and completely blocked the induction of long‐term potentiation and long‐term depression. The α2‐adrenoreceptor antagonist yohimbine (2 µm) reversed this effect. The α2‐adrenoreceptor agonist clonidine (10 µm) mimicked the effects of norepinephrine. The Gi/o‐protein inhibitor pertussis toxin (5 µg/mL) reversed the effect of clonidine. Long‐term depression was blocked in the presence of ω‐conotoxin GVIA, but not ω‐agatoxin IVA. Clonidine inhibited voltage‐activated Ca2+ currents mediated via N‐ or P/Q‐type Ca2+‐channels. The inhibitory action of clonidine on long‐term depression was reversed when inwardly rectifying K+‐channels were blocked by Ba2+ (300 µm). The present data suggest that α2‐adrenoreceptor activation impairs the induction of long‐term depression in the basolateral amygdala by a Gi/o‐protein‐mediated inhibition of presynaptic N‐type Ca2+‐channels and activation of inwardly‐rectifying K+‐channels.
The amygdalar circuit that acquires taste aversion memory differs from the circuit that extinguishes it
Authors: Bahar Amir , Samuel Anat , Hazvi Shoshi , Dudai Yadin
Published: May 2003

Experimental extinction is the decline in the frequency or intensity of a conditioned behaviour resulting from repetitive performance of the behaviour in the absence of the unconditioned stimulus or reinforcer (Pavlov, 1927). Ample behavioural evidence indicates that experimental extinction does not reflect unlearning of the original trace, but rather a relearning process, in which the new association of the conditioned stimulus with the absence of the original reinforcer comes to control behaviour (Rescorla, 1996). If experimental extinction is indeed learning rather than forgetting, are the neuronal circuits that subserve learning and extinction identical? We address this question by double dissociation analysis of the role of the central (CeA) and the basolateral (BLA) nuclei of the rat's amygdala in the acquisition and extinction, respectively, of conditioned taste aversion (CTA). Whereas local blockade of protein synthesis or β‐adrenergic receptors in the CeA blocks acquisition but not extinction of CTA, a similar intervention in the BLA blocks extinction but not acquisition. Hence, the amygdalar circuit that acquires taste aversion memory differs functionally from the circuit that extinguishes it.
Differential adaptive properties of accumbens shell dopamine responses to ethanol as a drug and as a motivational stimulus
Authors: Bassareo Valentina , De Luca Maria Antonietta , Aresu Marzia , Aste Alessandra , Ariu Teresa , Di Chiara Gaetano
Published: May 2003

Non‐adaptive activation of dopamine transmission in the nucleus accumbens shell by drugs of abuse has been attributed a fundamental role in the mechanism of drug addiction. In order to test this hypothesis, we compared in the same subject the effect of an addictive drug (ethanol) and of taste stimuli, including ethanol's own taste, on dialysate dopamine in the nucleus accumbens shell as an estimate of dopamine transmission and on taste reactivity as an expression of motivational valence. Ethanol was also monitored in the dialysates. In naive rats, intraoral infusion of a 20% sucrose + chocolate solution elicited a monophasic increase of dialysate dopamine immediately after the intraoral infusion. In contrast, intraoral infusion of 10% ethanol, 10% ethanol + 20% sucrose or 10% ethanol + 20% sucrose + chocolate solutions elicited a biphasic increase of nucleus accumbens dopamine with an early taste‐related rise and a late rise related to dialysate ethanol. Pre‐exposure to the ethanol solutions 24 h before resulted in the absence of the early dopamine rise and permanence of the late dopamine rise. This late dopamine rise was actually increased as compared with that of the nonpre‐exposed group when sucrose‐containing ethanol solutions were tested. The results indicate that single trial pre‐exposure to the ethanol solutions differentially affects the responsiveness of nucleus accumbens shell dopamine to the direct intracerebral action of ethanol and to the effect of its taste with potentiation, or no change of the first and abolition of the second. These observations point to the existence of major differences in the adaptive regulation of nucleus accumbens dopamine transmission in the shell after drug as compared with taste reward. These differences, in turn, are consistent with a role of nucleus accumbens shell dopamine in the mechanism of the behavioural effects of addictive drugs.
Effects of nicotine in the dopaminergic system of mice lacking the alpha4 subunit of neuronal nicotinic acetylcholine receptors
Authors: Marubio L. M. , Gardier A. M. , Durier S. , David D. , Klink R. , Arroyo‐Jimenez M. M. , McIntosh J. M. , Rossi F. , Champtiaux N. , Zoli M. , Changeux J‐P.
Published: May 2003

The mesostriatal dopaminergic system influences locomotor activity and the reinforcing properties of many drugs of abuse including nicotine. Here we investigate the role of the α4 nicotinic acetylcholine receptor (nAChR) subunit in mediating the effects of nicotine in the mesolimbic dopamine system in mice lacking the α4 subunit. We show that there are two distinct populations of receptors in the substantia nigra and striatum by using autoradiographic labelling with 125I α‐conotoxin MII. These receptors are comprised of the α4, β2 and α6 nAChR subunits and non‐α4, β2, and α6 nAChR subunits. Non‐α4 subunit‐containing nAChRs are located on dopaminergic neurons, are functional and respond to nicotine as demonstrated by patch clamp recordings. In vivo microdialysis performed in awake, freely moving mice reveal that mutant mice have basal striatal dopamine levels which are twice as high as those observed in wild‐type mice. Despite the fact that both wild‐type and α4 null mutant mice show a similar increase in dopamine release in response to intrastriatal KCl perfusion, a nicotine‐elicited increase in dopamine levels is not observed in mutant mice. Locomotor activity experiments show that there is no difference between wild‐type and mutant mice in basal activity in both habituated and non‐habituated environments. Interestingly, mutant mice sustain an increase in cocaine‐elicited locomotor activity longer than wild‐type mice. In addition, mutant mice recover from depressant locomotor activity in response to nicotine at a faster rate. Our results indicate that α4‐containing nAChRs exert a tonic control on striatal basal dopamine release, which is mediated by a heterogeneous population of nAChRs.
Cellular mechanisms of the trigeminally evoked startle response
Authors: Schmid Susanne , Simons Nadine S. , Schnitzler Hans‐Ulrich
Published: May 2003

The startle response is an important mammalian model for studying the cellular mechanisms of emotions and of learning. It consists of contractions of facial and skeletal muscles in response to sudden acoustic, tactile or vestibular stimuli. Whereas the acoustic startle pathway is well described, only a few recent studies have investigated the tactile startle pathway. It was proposed that there is a direct projection from the principal sensory nucleus to the central sensorimotor interface of the startle response, which is formed by the giant neurons in the caudal pontine reticular formation. We explored this projection in greater detail in vitro. Anterograde tracing in rat brain slices confirmed projections with large axon terminals from the ventral part of the principal sensory nucleus to the lateral caudal pontine reticular formation. Electrophysiological studies revealed a monosynaptic glutamatergic connection between principal sensory nucleus neurons and caudal pontine reticular formation giant neurons. The synapses displayed paired‐pulse facilitation at high‐frequency stimulation, and homosynaptic depression at 1 Hz stimulation. The latter form of plasticity is thought to underlie habituation of the startle response. Furthermore, postsynaptic currents in caudal pontine reticular formation giant neurons evoked by principal sensory nucleus neuron stimulation summed in a linear way with signals evoked by stimulation of auditory afferents. Synaptic plasticity and summation of synaptic currents correspond well with in vivo data previously published by other groups. We thus presume that these synapses mediate trigeminal input to the startle pathway.
Trace eyeblink conditioning in decerebrate guinea pigs
Authors: Kotani Sadaharu , Kawahara Shigenori , Kirino Yutaka
Published: May 2003

We investigated the trace eyeblink conditioning in decerebrate guinea pigs to elucidate the possible role of the cerebellum and brainstem in this hippocampus‐dependent task. A 350‐ms tone conditioned stimulus was paired with a 100‐ms periorbital shock unconditioned stimulus with a trace interval of either 0, 100, 250 or 500 ms. Decerebrate animals readily acquired the conditioned response with a trace interval of 0 or 100 ms. Even in the paradigm with a 500‐ms trace interval, which is known to depend critically on the hippocampus in all animal species examined, the decerebrate guinea pigs acquired the conditioned response, which had adaptive timing as well as in the other paradigms with a shorter trace interval. However, it took many more trials to learn in the 500‐ms trace paradigm than in the shorter trace interval paradigms, and the conditioned response expression was unstable from trial to trial. When decerebrate animals were conditioned step by step with a trace interval of 100, 250 and 500 ms, sequentially, they easily acquired the adaptive conditioned response to a 500‐ms trace interval. However, the frequency of conditioned responses decreased after the trace interval was shifted from 250 ms to 500 ms, which was not observed after the shift from 100 ms to 250 ms. These results suggest that the cerebellum and brainstem could maintain the ‘trace’ of the conditioned stimulus and associate it with the unconditioned stimulus even in the 500‐ms trace paradigm, but that the forebrain might be required for facilitating and stabilizing the association.
Expression of the ecto‐ATPase NTPDase2 in the germinal zones of the developing and adult rat brain
Authors: Braun Norbert , Sévigny Jean , Mishra Santosh K. , Robson Simon C. , Barth Stephan W. , Gerstberger Ruediger , Hammer Klaus , Zimmermann Herbert
Published: May 2003

In the adult nervous system, multipotential stem cells of the subventricular zone of the lateral ventricles generate neuron precursors (type‐A cells) that migrate via the rostral migratory stream to the olfactory bulb where they differentiate into neurons. The migrating neuroblasts are surrounded by a sheath of astrocytes (type‐B cells). Using immunostaining, in situ hybridization and enzyme histochemistry, we demonstrate that the ecto‐ATPase nucleoside triphosphate diphosphohydrolase 2 (NTPDase2) is expressed in the subventricular zone and the rostral migratory stream of the adult rat brain. This enzyme hydrolyses extracellular nucleoside triphosphates to the respective nucleoside diphosphates and is thought to directly modulate ATP receptor‐mediated cell communication. Double labelling for the astrocyte intermediate filament protein GFAP and the glial glutamate transporter GLAST identifies the NTPDase2‐positive cells as type‐B cells. During development the enzyme protein is first detected at E18, long before expression of the astrocyte marker GFAP. It gradually becomes expressed along the ventricular and subventricular zone of the brain, followed by complete retraction to the adult expression pattern at P21. NTPDase2 is transiently expressed in the outer molecular layer of the dentate gyrus and within the cerebellar white matter and is associated with select microvessels, tanycytes of the third ventricle, and subpial astrocytes of the adult brain. Our results suggest that NTPDase2 can serve as a novel marker for specifying subsets of cells during in vivo and in vitro studies of neural development and raise the possibility that ATP‐mediated signalling pathways play a role in neural development and differentiation.
Ionic currents underlying rhythmic bursting of ventral mossy cells in the developing mouse dentate gyrus
Authors: Jinno Shozo , Ishizuka Satoru , Kosaka Toshio
Published: May 2003

The electrophysiological properties of mossy cells were examined in developing mouse hippocampal slices using whole‐cell patch‐clamp techniques, with particular reference to the dorsoventral difference. Dorsal mossy cells exhibited a higher spontaneous excitatory postsynaptic potential (EPSP) frequency and larger maximal EPSP amplitude than ventral mossy cells. On the other hand, the blockade of synaptic inputs with glutamatergic and GABAergic antagonists disclosed a remarkable dorsoventral difference in the intrinsic activity: none (0/27) of the dorsal mossy cells showed intrinsic bursting, whereas the majority (35/47) of the ventral mossy cells exhibited intrinsic rhythmic bursting. To characterize the ionic currents underlying the rhythmic bursting of mossy cells, we used somatic voltage‐clamp recordings in the subthreshold voltage range. Ventral bursting cells possessed both hyperpolarization‐activated current (Ih) and persistent sodium current (INaP), whereas dorsal and ventral nonbursting cells possessed Ih but no INaP. Blockade of Ih with cesium did not affect the intrinsic bursting of ventral mossy cells. In contrast, the blockade of INaP with tetrodotoxin or phenytoin established a stable subthreshold membrane potential in ventral bursting cells. The current–voltage curve of ventral bursting cells showed a region of tetrodotoxin‐sensitive negative slope conductance between −55 mV and a spike threshold (≈ −45 mV). On the other hand, no subthreshold calcium conductances played a significant role in the intrinsic bursting of ventral mossy cells. These observations demonstrate the heterogeneous electrophysiological properties of hilar mossy cells, and suggest that the subthreshold INaP plays a major role in the intrinsic rhythmic bursting of ventral mossy cells.
The parieto‐collicular pathway: anatomical location and contribution to saccade generation
Authors: Gaymard B. , Lynch J. , Ploner C.J. , Condy C. , Rivaud‐Péchoux S.
Published: May 2003

The monkey lateral intraparietal area (LIP), involved in reflexive shifts of visual attention, has two main oculomotor outputs: towards frontal oculomotor areas and towards the superior colliculus. Recent studies suggest that these two outputs do not carry similar information. Direct LIP–collicular neurons would convey visual signals providing the oculomotor system with on‐line visuo‐spatial information. Parietal visuo‐spatial information regarding internal stimuli would access the brainstem oculomotor circuitry through a parieto‐frontal network. Consequently, an interruption of parieto‐tectal neurons should affect reflexive saccades towards unpredictable targets and have little or no effect on saccades towards predictable or memorised stimuli. In order to test this hypothesis in humans, we have determined in rhesus monkeys the location of LIP–tectal fibres in the region of the internal capsule, and found that these neurons travel in the most posterior region of the posterior limb of the internal capsule. We have then tested, in seven patients with a small lesion involving this region, several oculomotor paradigms designed to determine the influence of spatial predictability on saccade accuracy and the ability to withhold reflexive saccades. In all patients, saccade accuracy was affected in unpredictable conditions but was normal when target location could be predicted or memorised. Reflexive saccade inhibition was affected only in the three patients in whom the capsular lesion had the most anterior extent. These results therefore support in humans the hypothesis that parieto‐tectal neurons (i) transmit an on‐line signal that is used by the oculomotor system for reflexive saccade triggering, (ii) are not crucial for the computation of internally guided saccades and (iii) are not crucial for reflexive saccade inhibition.
Cerebral regions processing first‐ and higher‐order motion in an opposed‐direction discrimination task
Authors: Dupont P. , Sáry G. , Peuskens H. , Orban G. A.
Published: May 2003

Using PET, we studied the processing of different types of motion in an opposed‐direction discrimination task. We used first‐order motion and two types of higher‐order motion (presented as moving gratings with stripes defined by flickering texture and kinetic boundaries, respectively). In these experiments, we found that all types of motion activate a common set of cortical regions when comparing a direction discrimination task to a detection of the dimming of the fixation point. This set includes left hV3A, bilateral hMT/V5+ and regions in the middle occipital gyrus, bilateral activations in the posterior and anterior parts of the intraparietal sulcus, bilateral precentral gyrus, medial frontal cortex and regions in the cerebellum. No significant differences were observed between different types of motion, even at low statistical thresholds. From this we conclude that, under our experimental conditions, the same cerebral regions are involved in the processing of first‐order and higher‐order motion in an opposed‐direction discrimination task.
Morphological and molecular heterogeneity in release sites of single neurons
Authors: Morgenthaler Florence D. , Knott Graham W. , Floyd Sarria J.‐C. , Wang Xin , Staple Julie K. , Catsicas Stefan , Hirling Harald
Published: May 2003

We have previously shown that labelling intensities for synaptic proteins vary strongly among synaptic boutons. Here we addressed the questions as to whether there are heterogeneous levels of integral membrane synaptic vesicle proteins at distinct active release sites of single neurons and if these sites possess the ultrastructural features of synapses. By double‐immunostaining with specific antibodies against synaptophysin, synaptotagmin I, VAMP1 and VAMP2, we identified different relative levels of these integral membrane proteins of synaptic vesicles in comparison to boutons of the same rat cortical neuron. This heterogeneity could also be observed between the two isoforms VAMP1 and VAMP2. By studying pairs of these proteins implicated in neurotransmitter release, including both VAMP isoforms, we also show that the sites that contained predominantly one protein were nevertheless functional, as they internalized and released FM1‐43 upon potassium stimulation. Using electron microscopy, we show that these active sites could have either synaptic specializations, or the features of vesicle‐containing varicosities without a postsynaptic target. Different varicosities of the same neuron showed different intensities for synaptic vesicle proteins; some varicosities were capable of internalizing and releasing FM1‐43, while others were silent. These results show that integral membrane synaptic vesicle proteins are differentially distributed among functional release sites of the same neuron.
The mid‐ventrolateral prefrontal cortex: insights into its role in memory retrieval
Authors: Kostopoulos Penelope , Petrides Michael
Published: May 2003

Although it is widely known that the prefrontal cortex plays a role in memory, the specific contribution of particular prefrontal regions in mnemonic functions remains controversial. The present investigation examined whether the mid‐ventrolateral prefrontal cortex is selectively involved in active memory retrieval in situations in which mnemonic traces are embedded in ambiguous relations and automatic recollection cannot lead to successful retrieval. Thirteen subjects participated in this event‐related functional magnetic resonance imaging experiment. Throughout the scanning session, trials belonging to an experimental and a control condition were administered in a pseudorandom fashion. During the encoding phase of any particular trial, subjects were presented with a stimulus‐complex that was a combination of a face and a spatial location on the screen. In the experimental active retrieval condition, a question cue following the encoding phase instructed the subjects to retrieve selectively one of the two aspects of the encoded stimulus‐complex, i.e. the face or the location. In the control condition, the question cue that followed the encoding phase instructed the subjects simply to recall the initially presented stimulus‐complex, so as to be able to make a decision during the test phase based on simple stimulus familiarity. The comparison of the signal obtained during the retrieval phase of these two conditions yielded an increase in activity selective to the right mid‐ventrolateral prefrontal region. These results therefore establish a specific link between the mid‐ventrolateral prefrontal cortex and active retrieval mechanisms.
Early (E12) cortical progenitors can change their fate upon heterotopic transplantation
Authors: Gaillard Afsaneh , Nasarre Cécile , Roger Michel
Published: May 2003

To help understand how the cortical map is set up during the early stages of corticogenesis, we have examined the developmental fate of embryonic day (E) 12 cortical progenitors in the rat. We have analysed the pattern of thalamic connections and cytoarchitectonic organization developed by progenitor cells removed at E12 from the presumptive parietal or occipital cortex and grafted into the parietal cortex of newborn hosts. Occipital progenitors grafted into the parietal cortex differentiated into neurons that developed reciprocal connections with the ventrobasal complex of the host thalamus. They could also form barrel‐like structures, within which axons of the ventrobasal complex were distributed in dense patches. Some of these barrel‐like structures were arranged in rows. Moreover, these progenitors failed to develop characteristic traits of occipital cortex cells as they did not establish connections with the dorsal lateral geniculate nucleus. We propose that cortical progenitors are not committed at E12 and, upon heterotopic transplantation, have the capacity to respond to local cues and to subsequently differentiate and maintain major phenotypic characteristics of neurons in their new environment. Only early progenitors are multipotent. By E13/E14, indeed, most cortical cells become irreversibly committed and upon heterotopic transplantation differentiate neurons with phenotypic characteristics of their cortical site of origin (Pinaudeau et al., 2000, Eur. J. Neurosci., 12, 2486–2496).
Noxious‐evoked c‐fos expression in brainstem neurons immunoreactive for GABAB, µ‐opioid and NK‐1 receptors
Authors: Pinto Marta , Lima Deolinda , Castro‐Lopes José , Tavares Isaura
Published: May 2003

Modulation of nociceptive transmission at the brainstem involves several neurochemical systems. The precise location and specific characteristics of nociceptive neurons activated in each system was never reported. In this study, the presence of GABAB, µ‐opioid, and neurokinin‐1 (NK‐1) receptors in brainstem nociceptive neurons was investigated by double‐immunocytochemical detection of each receptor and noxious‐evoked induction of the c‐fos proto‐oncogene. Noxious cutaneous mechanical stimulation significantly increased the proportions of neurons double‐labelled for Fos and GABAB receptors in several brainstem regions, namely, the reticular formation of the caudal ventrolateral medulla (VLMlat and VLMrf), lateral reticular nucleus, spinal trigeminal nucleus, pars caudalis (Sp5C), nucleus of the solitary tract, dorsal reticular nucleus, ventral reticular nucleus, raphe obscurus nucleus and dorsal parabrachial nucleus (DPB). For µ‐opioid receptors, the proportions of double‐labelled neurons in noxious‐stimulated animals were higher than in controls only in the VLMlat, VLMrf, Sp5C, DPB and A5 noradrenergic cell group. As for the NK‐1 receptor, no significant differences were found between control and stimulated animals. According to these results, neurons expressing GABAB, µ‐opioid and NK‐1 receptors at several pain control centres of the brainstem are differentially involved in processing nociceptive mechanical input. The data provide the definition of new supraspinal targets for selective modulation of nociceptive neurons in order to define better strategies of pain control.
Role of specific muscarinic receptor subtypes in cholinergic parasympathomimetic responses, in vivo phosphoinositide hydrolysis, and pilocarpine‐induced seizure activity
Authors: Bymaster Frank P. , Carter Petra A. , Yamada Masahisa , Gomeza Jesus , Wess Jürgen , Hamilton Susan E. , Nathanson Neil M. , McKinzie David L. , Felder Christian C.
Published: May 2003

Muscarinic agonist‐induced parasympathomimetic effects, in vivo phosphoinositide hydrolysis and seizures were evaluated in wild‐type and muscarinic M1–M5 receptor knockout mice. The muscarinic agonist oxotremorine induced marked hypothermia in all the knockout mice, but the hypothermia was reduced in M2 and to a lesser extent in M3 knockout mice. Oxotremorine‐induced tremor was abolished only in the M2 knockout mice. Muscarinic agonist‐induced salivation was reduced to the greatest extent in M3 knockout mice, to a lesser degree in M1 and M4 knockout mice, and was not altered in M2 and M5 knockout mice. Pupil diameter under basal conditions was increased only in the M3 knockout mice. Pilocarpine‐induced increases in in vivo phosphoinositide hydrolysis were completely absent in hippocampus and cortex of M1 knockout mice, but in vivo phosphoinositide hydrolysis was unaltered in the M2–M5 knockout mice. A high dose of pilocarpine (300 mg/kg) caused seizures and lethality in wild‐type and M2–M5 knockout mice, but produced neither effect in the M1 knockout mice. These data demonstrate a major role for M2 and M3 muscarinic receptor subtypes in mediating parasympathomimetic effects. Muscarinic M1 receptors activate phosphoinositide hydrolysis in cortex and hippocampus of mice, consistent with the role of M1 receptors in cognition. Muscarinic M1 receptors appear to be the only muscarinic receptor subtype mediating seizures.
Electroanatomic Mapping of Endocardial Right Ventricular Activation as a Guide for Catheter Ablation in Patients with Arrhythmogenic Right Ventricular Dysplasia
Authors: REITHMANN CHRISTOPHER , HAHNEFELD ANTON , REMP THOMAS , DORWARTH UWE , DUGAS MARTIN , STEINBECK GERHARD , HOFFMANN ELLEN
Published: May 2003

Arrhythmogenic right ventricular dysplasia is a structural heart disease characterized by fibrofatty degeneration of right ventricular myocardium and arrhythmias of right ventricular origin. The aim of this study was to characterize endocardial right ventricular activation by electroanatomic mapping as a guide for catheter ablation in patients with arrhythmogenic right ventricular dysplasia. Electroanatomic mapping and entrainment procedures were performed in 5 patients with arrhythmogenic right ventricular dysplasia. Endocardial mapping during ventricular tachycardia demonstrated a focal activation pattern with radial spreading of activation from a site of earliest ventricular activation in all directions. Right ventricular activation time (127 ± 34 ms) was markedly shorter than tachycardia cycle length (415 ± 92 ms). The site of earliest ventricular activation was found in an aneurysmal outflow tract (n = 2), at the border of aneurysms near the tricuspid annulus (n = 2), and at the apex of the right ventricle (n = 1). Entrainment mapping criteria of these areas of earliest endocardial activity were consistent with exit sites of a reentrant circuit in an area of abnormal myocardium. Fractionated potentials were found 61 ± 29 ms before the onset of the QRS complex at these sites. Catheter ablation rendered the “clinical“ ventricular tachycardia noninducible in four patients but “nonclinical” faster ventricular tachycardias were inducible in three patients. During the follow‐up of 7 ± 3 months after ablation, the frequency of therapies in 4 patients with an implantable cardioverter defibrillator decreased from 49 ± 61 episodes per month before ablation, to 0.3 ± 0.5 episodes per month after ablation (P < 0.05). Electroanatomic mapping during ventricular tachycardia facilitates localization of exit sites in relation to aneurysms in diseased right ventricle and may guide catheter ablation in patients with arrhythmogenic right ventricular dysplasia. (PACE 2003; 26:1308–1316)
Immediate Reinitiation of Atrial Tachyarrhythmias after Spontaneous Restoration of Sinus Rhythm in Patients with an Implanted Monitoring Device
Authors: ISRAEL CARSTEN W. , EHRLICH JOACHIM R. , GRÖNEFELD GERIAN , LI YI‐GANG , HOHNLOSER STEFAN H.
Published: May 2003

Immediate reinitiation of atrial tachyarrhythmia (IRAT) has been observed after cardioversion. After spontaneous restoration of sinus rhythm (SR), incidence and characteristics of IRAT have not been described. Therefore, in patients with atrial tachyarrhythmias (ATs) and bradycardia, a pacemaker with dedicated memory functions was implanted. Devices were interrogated after 1 month and stored episodes of AT were analyzed: incidence of IRAT, duration and rate of the preceding episode, sinus rate before AT, coupling interval of atrial premature beats (APBs) initiating AT, and incidence of repetitive APBs. A potential association with IRAT was assessed for clinical characteristics. In 36 of 68 patients, stored electrograms confirmed correct detection of AT onset and termination in 545 episodes. IRAT was present in 212 (39%, 24 patients) episodes of AT. Episodes of AT preceding IRAT were longer than those before non‐IRAT (156 vs 46 s,

P < 0.001

), and occurred during a higher atrial rate before onset of AT (cycle length

775 ± 111

vs

856 ±133 ms, P < 0.001

). The coupling interval of APBs initiating IRAT was shorter (

502 ± 83

vs

538 ± 89  ms; P < 0.001

) while the percentage of episodes with repetitive APBs before AT onset and the median atrial cycle length of the preceding AT were not different. On stepwise logistic regression analysis, none of the clinical factors evaluated independently predicted IRAT. In conclusion, IRAT is frequent after spontaneous restoration of SR. Changes of atrial electrophysiological properties promoting IRAT may already develop during AT of short duration. (PACE 2003; 26:1317–1325)
Electrocardiographic Ventricular Repolarization Parameters in Chronic Chagas' Disease as Predictors of Asymptomatic Left Ventricular Systolic Dysfunction
Authors: SALLES GIL F. , CARDOSO CLAUDIA R.L. , XAVIER SERGIO S. , SOUSA ANDREA S. , HASSLOCHER‐MORENO ALEJANDRO
Published: May 2003

Electrocardiographic repolarization parameters are potential markers of arrhythmogenic risk and have not been evaluated in Chagas' disease. The aim of this report was to investigate their associations with LV systolic function assessed by two‐dimensional echocardiography. In a cross‐sectional study involving 738 adult outpatients in the chronic phase of Chagas' disease, maximal QTc and T wave peak‐to‐end (TpTe) intervals, and QT, QTapex (QTa), JT and TpTe interval dispersions, and variation coefficients were measured and calculated from 12‐lead standard ECGs. Clinical, radiological, ECG, and echocardiographic data were recorded. In bivariate statistical analysis, all repolarization parameters were significantly increased in patients with moderate or severe LV systolic dysfunction, and these patients showed more clinical, radiologic, and ECG abnormalities. Receiver operating characteristic curve analysis demonstrated that isolatedly QTd had the best predictive performance for LV dysfunction, with an 80% specificity and 67% sensitivity for values >60 ms in the subgroup of chagasic patients with abnormal ECGs and no heart failure. Multivariate logistic regression selected, as the best predictive model for LV dysfunction in this subgroup of patients, the presence of cardiomegaly on chest X ray (OR 14.06, 95% CI, 5.54–35.71), QTd > 60 ms (OR 9.35, 95% CI, 4.01–21.81), male gender (OR 7.70, 95% CI, 2.98–19.91) and the presence of frequent premature ventricular contractions (PVCs) on ECG (OR 4.06, 95% CI, 1.65–9.97). This model showed 90% specificity and 71% sensitivity. In conclusion, QTd was associated to LV systolic function and could be used to predict asymptomatic dysfunction in chronic Chagas' disease. The presence of cardiomegaly, frequent PVCs, and male sex refined LV function stratification in these patients. (PACE 2003; 26:1326–1335)
Mechanisms of Onset of Atrial Fibrillation:
Authors: GUYOMAR YVES , THOMAS OLIVIER , MARQUIÉ CHRISTELLE , JARWE MOUSTAPHA , KLUG DIDIER , KACET SALEM , CARLIOZ ROLAND , FERRIER ALAIN , FOSSATI FRÉDÉRIC , GUÉRIN STÉPHANIE , HEULS SÉBASTIEN , GRAUX PIERRE
Published: May 2003

The aim of this study was to analyze the onset mechanisms of atrial tachyarrhythmias using a dedicated diagnostic system in 83 recipients of DDDR pacemakers implanted for standard clinical indications. The pulse generator was programmed in DDD mode, at 60 beats/min, and the diagnostic instrument was programmed to document atrial tachyarrhythmic episodes at rates >200 beats/min. Onset mechanism was defined as the combination of ambient rhythm and trigger. Various underlying rates and rhythms patterns, including tachycardia, increasing frequency of premature atrial complex (PAC), underlying heart rate increase, restart, and no specific underlying rhythm, and various triggers, including single, multiple, or short runs of PACs, sudden rate decrease, and sudden onset of atrial tachyarrhythmia were included in the combined classification. Atrial tachyarrhythmic episodes were documented on one follow‐up interrogation in 48 of the 83 patients. The pacing indications consisted of high degree atrioventricular block in 19 patients, bradycardia‐tachycardia syndrome in 22, and isolated sinus node dysfunction in 6 patients. The onset mechanisms of 318 episodes were recorded and analyzed. A variety of triggers were observed in 33 of the 48 patients, and 39 patients had various ambient rhythms. Among 20 documented onset mechanisms, the most common were increasing frequency of PAC + short runs (17%), no specific ambient rhythm + sudden onset (24%), and increasing frequency of PAC + sudden onset (12%). There were wide intra‐ and interpatient variations in onset mechanisms, suggesting that state‐of‐the‐art pacemakers should represent versatile diagnostic tools and offer flexible pacing methods to refine the management of atrial tachyarrhythmias. (PACE 2003; 26:1336–1341)
Pulmonary Vein Internal Electrical Activity Does Not Contribute to the Maintenance of Atrial Fibrillation
Authors: NDREPEPA GJIN , SCHNEIDER MICHAEL A.E. , KARCH MARTIN R. , WEBER STEFAN , SCHREIECK JÜRGEN , SCHÖMIG ALBERT , SCHMITT CLAUS
Published: May 2003

Whether the electrical activity generated in the pulmonary veins (PVs) during atrial fibrillation (AF) contributes to the maintenance of arrhythmia is not known. The study population consisted of 22 patients (mean age 58 ± 9.5 years, 16 men) with persistent (12 patients) or intermittent (10 patients) AF. Mapping of the left atrium (LA) was performed with a 64‐electrode basket catheter. PVs were mapped simultaneously with the LA with a quadripolar catheter. PV were defined as arrhythmogenic (if frequent ectopic activity induced AF) or nonarrhythmogenic (if no ectopic activity was observed during the procedure). AF cycle lengths in arrhythmogenic and nonarrhythmogenic PV were 130 ± 50 ms and 152 ± 42 ms, respectively

(P < 0.001)

. Both were significantly longer than simultaneous AF activity recorded from the posterior wall of the LA

(116 ± 49 ms, P < 0.001)

. AF cycle lengths in arrhythmogenic PVs as compared to nonarrhythmogenic PVs were: right superior PV 125 ± 49 ms versus 148 ± 51 ms ; left superior PV 140 ± 52 ms versus 161 ± 30 ms ; left inferior PV 127 ± 48 ms versus 147 ± 45 ms ; and right inferior PV 129 ± 38 versus 152 ± 44 ms (

P < 0.001

for all four comparisons). AF activity in the PV was more organized than in the posterior wall of the LA and the veins were activated in a proximal‐to‐distal direction during sustained AF episodes. In patients with AF not related to rheumatic heart disease, the posterior wall of the LA has faster activity than the PVs. The AF activity generated inside the PV during sustained AF episodes originates from the posterior wall of the LA rather than from focal firing. (PACE 2003; 26:1356–1362)
Dissociated Activity and Pulmonary Vein Fibrillation Following Functional Disconnection:
Authors: WILLEMS STEPHAN , WEISS CHRISTIAN , RISIUS TIM , ROSTOCK THOMAS , HOFFMANN MATTHIAS , VENTURA RODOLFO , MEINERTZ THOMAS
Published: May 2003

The present study sought to investigate the electrophysiological properties of isolated pulmonary veins following successful radiofrequency (RF) catheter ablation in patients with paroxysmal atrial fibrillation (PAF). Overall, 71 pulmonary veins in 37 consecutive patients (age:

56 ± 9  years

) with recurrent PAF were targeted for RF ablation at the ostial region in order to achieve a complete functional block. Following disconnection, the incidence of dissociated pulmonary vein (PV) activity and its response to orciprenalin were studied. RF ablation abolished conduction in 67 (94%) of 71 potentially arrhythmogenic PVs after a mean of

10.7 ± 6.4  RF

applications for each PV. After ablation, spontaneous dissociated automatic activity (9 to 52 beats/min, median 27) was found in 6 out of 67 isolated PVs (left superior:

n = 1

, left inferior:

n = 1

, right superior:

n = 2

, common left PV:

n = 2

). Slight acceleration (13 to 68 beats/min, median 29) of dissociated PV activity was observed during infusion of orciprenalin. Following isolation, initiation of sustained or nonsustained local fibrillation was recorded in only two cases of the common left sided PV with preceding automatic activity. In one patient PV fibrillation occurred during orciprenalin infusion following a repetitive response to a dissociated automatic rhythm with increasing duration as well as destabilization. In the other patient, PV fibrillation occurred immediately after the occurrence of PV automaticity. Slow dissociated automatic rhythms are detectable within 9% of disconnected PVs. The unique anatomic substrate of common left PVs seem to favor the occurrence of local fibrillation following isolation. The initiation pattern of fibrillation within the isolated PV has pathophysiological implications and underlines the contribution of multiple factors to the onset and sustenance of PAF. (PACE 2003; 26:1363–1370)
Dilatation of the Pulmonary Veins in Atrial Fibrillation:
Authors: KNACKSTEDT CHRISTIAN , VISSER LAURENT , PLISIENE JURGITA , ZARSE MARKUS , WALDMANN MATTHIAS , MISCHKE KARL , KOCH KARL‐CHRISTIAN , HOFFMANN RAINER , FRANKE ANDREAS , HANRATH PETER , SCHAUERTE PATRICK
Published: May 2003

Ectopic beats originating from sleeves of atrial tissue within the pulmonary veins (PVs) can induce and sustain paroxysmal atrial fibrillation (AF). Left atrial stretch and dilatation favors the development of atrial ectopy and AF. Similarly, PV dilatation, if present, might trigger PV ectopy in patients with AF. This study was designed to evaluate whether PV dilatation is present in patients with nonfocal AF and whether the PV diameter correlates to the left atrial diameter (LAD). The diameters of the right superior (RSPV) and left superior PV (LSPV) were measured at the ostium and at a depth of 1 cm in 170 patients (AF, n = 75 ; sinus rhythm [SR], n = 95) using transesophageal echocardiography. The LAD was determined by transthoracic echocardiography. The diameters of the PVs were significantly larger in patients with AF than in patients with SR (LSPVostium: AF 13.6 ± 3.5 mm vs SR 10.6 ± 2.7 mm, P < 0.001 ; LSVP1cm: AF 12.5 ± 2.9 mm vs SR 10.2 ± 2.5 mm, P < 0.001 ; RSPVostium, AF 13.9 ± 3.5 mm vs SR 11.7 ± 2.9 mm, P < 0.001 ; RSVP1cm: AF 12.8 ± 2.8 mm vs SR 10.6 ± 2.6 mm, P < 0.05). Similarly, LAD was larger in patients with AF (44.7 ± 7.7 mm) as compared to patients with SR (38.8 ± 6.8 mm, P < 0.001). Neither for the SR nor the AF group did the PV size correlate to the LAD. AF is associated with a significant enlargement of the RSPV, LSPV, and LAD. There is no correlation between LAD and PV diameters. This raises the question whether PV dilatation in patients with AF is a cause or a consequence of AF and whether it may contribute to the development and perpetuation of AF. (PACE 2003; 26:1371–1378)
Increasing Power Versus Duration for Radiofrequency Ablation with a High Superfusate Flow:
Authors: GUY DUNCAN J.R. , BOYD ANITA , THOMAS STUART P. , ROSS DAVID L.
Published: May 2003

Radiofrequency (RF) ablation of pulmonary veins (PVs) is a new treatment for atrial fibrillation. Low energy ablation is usually used for this procedure. The effect of superfusate flow on lesion formation in this setting has not been studied previously. We examined lesion dimensions and intramural temperatures with varying powers and duration of RF application in this high flow environment. Ablation of fresh bovine hearts was performed with a 4‐mm tip RF catheter in temperature control mode, target temperature 50°C. At power levels of 20 W, 30 W, 40 W, and 50 W, effects of PV flow (no flow or 1 L/min) and 60‐ and 120‐second durations were tested. Tissue temperatures were recorded at depths of 1, 4, 7, and 10 mm. Without flow, no lesions were created. The lowest power setting for lesion creation was 30 W at 60 seconds and 20 W at 120 seconds. Increasing power from 30 W to 50 W for 60 seconds increased lesion depth 0.7 mm (SE 0.3),

P = 0.03

and 2.5 mm (SE 0.6),

P = 0.003

, at 120 seconds. Increasing RF application duration from 60 to 120 seconds increased depth for 30 W by 0.9 mm (SE 0.5),

P = NS

, 40 W 1.7 mm (SE 0.4),

P = 0.002

, and 50 W 2.6 mm (SE 0.5),

P < 0.001

. Power of 50 W for 60 seconds and >30 W for 120 seconds created lesions deeper than the wall thickness of a PV. Flow is necessary for creation of lesions with low power, low tip temperature RF ablation. When a resistant site to ablation is encountered, increasing duration of ablation is best for increasing lesion depth. Higher power has the potential to create lesions deeper than the PV wall and may increase the risk of complications. (PACE 2003; 26:1379–1385)
An Atypical Atrial Flutter of Focal Origin:
Authors: OUALI SANA , ANSELME FREDERIC , SAVOURE ARNAUD , CRIBIER ALAIN
Published: May 2003

We report a case of focal atrial tachycardia with appearance suggestive of atypical atrial flutter in a 57‐year‐old man. Based on ECG criteria, tachycardia was misclassified as atypical atrial flutter. The electrophysiological study using a noncontact mapping system revealed a focal activity within the left upper pulmonary vein ostium. This case highlights the limitations of standard electrocardiographic and electrophysiological classifications of regular atrial tachycardia. This report also shows the relevance of new mapping techniques in the successful mapping and ablation of these arrhythmias, even those arising within the left atrium. (PACE 2003; 26:1410–1412)
Electrophysiological Demonstration of Dissociation of Pulmonary Vein Potentials Through Electroanatomically Guided Circumferential Ablation
Authors: BERTAGLIA EMANUELE , ZOPPO FRANCO , D'ESTE DANIELE , PASCOTTO PIETRO
Published: May 2003

A 57‐year‐old woman with frequent isolated and repetitive premature atrial contractions initiating paroxysmal atrial fibrillation, underwent electrophysiological study and catheter ablation. A real‐time three‐dimensional map of the left atrium was reconstructed using a nonfluoroscopic navigation system. By means of a deflectable decapolar catheter, the left superior pulmonary vein (PV) was identified as the arrhythmogenic vein, and PV potentials were found in the left inferior and right superior veins. Ablation was performed under electroanatomic guidance. After circumferential ablation outside the PV ostia, dissociation of PV potentials was obtained in the left superior vein, and PV potentials were eliminated in the other two veins. (PACE 2003; 26:1413–1416)
Termination of Persistent Atrial Fibrillation Resistant to Cardioversion by a Single Radiofrequency Application
Authors: HERWEG BENGT , KOWALSKI MARCIN , STEINBERG JONATHAN S.
Published: May 2003

This report describes the termination of persistent AF refractory to multiple cardioversions and antiarrhythmic therapy in a patient without structural heart disease, with a single radiofrequency application delivered in the left upper pulmonary vein. The observations and failure of repeated internal and external cardioversion suggest a rapidly firing arrhythmia focus sustaining atrial fibrillation amenable to curative pulmonary vein ablation. (PACE 2003; 26:1420–1423)
Roxithromycin Induced Torsade de Pointes in a Patient with Complex Congenital Heart Disease and Complete Atrioventricular Block
Authors: PROMPHAN WORAKAN , KHONGPHATTHANAYOTHIN APICHAI , HORCHAIPRASIT KRIANGSAK , BENJACHOLAMAS VICHAI
Published: May 2003

We reported a 6‐year‐old girl who developed torsade de pointes (TdP) after taking roxithromycin. The patient had congenital complete heart block and complex cyanotic heart disease. Before taking roxithromycin, her corrected QT interval (QTc) was 0.39 second with a ventricular rate of 55–60 beats/min. Repetitive bursts of TdP with prolonged QT interval (

QTc = 0.55  s

) developed after taking roxithromycin. After stopping the medication, her QT interval normalized (

QTc = 0.38  s

). This case demonstrated the potential of roxithromycin in causing TdP especially in a patient with other risk factors for prolong QT interval and TdP. (PACE 2003; 26:1424–1426)
Cystic fibrosis‐related diabetes
Authors: Mackie A. D. R. , Thornton S. J. , Edenborough F. P.
Published: May 2003

Diabetes mellitus (DM) has been recognized as a complication of cystic fibrosis (CF) for almost 50 years and commonly develops around 20 years of age. The prevalence increases with age and, with improved survival of those with CF, approaches 30% in certain centres. Its development appears to have a significant impact on pulmonary function and may increase mortality by up to six‐fold. Subjects with CF are rarely ketosis‐prone and phenotypically lie between Type 1 and Type 2 DM. Microvascular complications are recognized, although paucity of data does not permit a clear description of their natural history. An annual oral glucose tolerance test from the age of 10 years is recommended for screening, but logistical difficulties have led some groups to develop specific algorithms to aid diagnosis. Insulin sensitivity in CF is much debated and may depend upon the degree of glucose intolerance. Insulin resistance occurs in the presence of infection, corticosteroid usage and hyperglycaemia, whilst hepatic insulin resistance is considered an adaptation to CF. There is no universal consensus on the treatment of hyperglycaemia. With increased longevity of individuals with CF, greater numbers will develop diabetes and the diabetes physician is destined to play a greater role in the multidisciplinary CF team.

Diabet. Med. 20, 425–436 (2003)