Effects of Different n6/n3 PUFAs Dietary Ratio on Cardiac Diabetic Neuropathy.

We studied the influence of experimentally induced DM1, in combination with different dietary n6:n3 polyunsaturated fatty acid (PUFA) ratios on different types of nerve fibers in rat myocardium, in order to reveal whether protective/unfavorable effects of different PUFAs on myocardial function in diabetic patients could be a (partial) repercussion of their effect on the changes in cardiac innervation. The control group (c) and diabetic group (stz) were fed with an n6/n3 ratio of ≈7; the diet of the stz+n6 group had an n6/n3 ratio ≈60, while the diet for the stz+DHA group contained 2.5% of fish oil (containing 16% eicosapentaenoic acid-EPA and 19% docosahexaenoic acid-DHA), n6/n3 ratio of ≈1. DM1 was induced by i.p. injection of streptozotocin (55 mg/kg) and rats were euthanized 30 days after induction. Immunohistochemistry was used for the detection and quantification of different types of neuronal fibers in the cardiac septum. We found changes in cardiac innervations characteristics for the initial phase of experimental DM1, which manifested as an increase in total number and area density of all neuronal fibers, measured by Pgp9.5 immunoreactivity. By detailed analysis, we found that this increase consisted mostly of heavy myelinated NF200 immunoreactive fibers and TH immunoreactive sympathetic fibers, while the density of ChAT immunoreactive parasympathetic fibers decreased. In the deep (middle) part of the myocardium, where rare fibers (of all studied types) were found, significant differences were not found. Surprisingly, we found a more consistent protective effect of n6 PUFAs, in comparison to n3 PUFAs supplementation. These results may provide a better understanding of the potential impacts of different PUFA ratios in the diet of diabetic patients on cardiac innervation and genesis and outcome of diabetic autonomic cardiomyopathy.

Cardiac sympathetic denervation predicts PD in at-risk individuals.

INTRODUCTION: By the time a person develops the motor manifestations of Parkinson's disease (PD), substantial loss of nigrostriatal dopamine neurons has already occurred. There is great interest in identifying biomarkers that can detect pre-clinical PD. Braak's neuropathological staging concept imputes early autonomic involvement. Here we report results from a small prospective cohort study about the utility of neuroimaging evidence of cardiac sympathetic denervation in predicting PD among individuals with multiple PD risk factors. METHODS: Subjects provided information about family history of PD, olfactory dysfunction, dream enactment behavior, and orthostatic hypotension at a protocol-specific website. From this pool, 27 people with at least 3 risk factors confirmed underwent cardiac 18F-dopamine positron emission tomographic scanning and were followed for at least 3 years. Interventricular septal and left ventricular free wall concentrations of 18F-dopamine-derived radioactivity were measured. RESULTS: Of the 27 subjects, 4 were diagnosed with PD within the 3-year follow-up period (Pre-Clinical PD group); 23 risk-matched (mean 3.2 risk factors) subjects remained disease-free (No-PD group). Compared to the No-PD group, the Pre-Clinical PD group had lower initial values for septal and free wall concentrations of 18F-dopamine-derived radioactivity (p = 0.0248, 0.0129). All 4 Pre-Clinical PD subjects had evidence of decreased cardiac sympathetic innervation in the interventricular septum or left ventricular free wall, in contrast with 3 of 23 (13%) No-PD subjects (p = 0.0020 by Fisher's exact test). CONCLUSION: People with multiple PD risk factors and diagnosed with PD within 3 years have evidence of antecedent cardiac sympathetic denervation. The findings fit with Braak's staging concept.

Distribution, structure and projections of the frog intracardiac neurons.

Histochemistry for acetylcholinesterase was used to determine the distribution of intracardiac neurons in the frog Rana temporaria. Seventy-nine intracardiac neurons from 13 frogs were labelled iontophoretically by the intracellular markers Alexa Fluor 568 and Lucifer Yellow CH to determine their structure and projections. Total neuronal number per frog heart was (Mean ± SE) 1374 ± 56. Largest collections of neurons were found in the interatrial septum (46%), atrioventricular junction (25%) and venal sinus (12%). Among the intracellularly labelled neurons, we found the cells of unipolar (71%), multipolar (20%) and bipolar (9%) types. Multiple processes originated from the neuron soma, hillock and proximal axon. These processes projected onto adjacent neuron somata and cardiac muscle fibers within the interatrial septum. Average total length of the processes from proximal axon was 348 ± 50 µm. Average total length of processes from soma and hillock was less, 118 ± 27 µm and 109 ± 24 µm, respectively. The somata of 59% of neurons had bubble- or flake-shaped extensions. Most neurons from the major nerves in the interatrial septum sent their axons towards the ventricle. In contrast, most neurons from the ventral part of the interatrial septum sent their axons towards the atria. Our findings contradict to a view that the frog intracardiac ganglia contain only non-dendritic neurons of the unipolar type. We conclude that the frog intracardiac neurons are structurally complex and diverse. This diversity may account for the complicated integrative functions of the frog intrinsic cardiac ganglia.

Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension.

BACKGROUND: We have reported previously that the sympathetic nervous system is activated in patients with pulmonary arterial hypertension (PAH), and that this is only partly explained by a decrease in arterial oxygenation. Possible causes for increased muscle sympathetic nerve activity (MSNA) in patients with PAH include right atrial distension and decreased cardiac output. Both may be improved by atrial septostomy, but this intervention also further decreases arterial oxygenation. In the present study, we wanted to investigate the effect of atrial septostomy on MSNA in patients with PAH. METHODS: We recorded BP, heart rate (HR), arterial O2 saturation (SaO2), and MSNA before and after atrial septostomy in PAH patients (mean [+/- SE] age, 48 +/- 5 years) and in closely matched control subjects. Measurements were also performed after septostomy, while SaO2 was brought to the preprocedure level by supplemental O2 therapy. RESULTS: Compared to the control subjects (n = 10), the PAH patients (n = 11) had a lower mean BP (75 +/- 2 vs 96 +/- 3 mm Hg, respectively; p < 0.001), lower mean SaO2 (92 +/- 1% vs 97 +/- 0%, respectively; p < 0.001), increased mean HR (84 +/- 4 vs 68 +/- 3 beats/min; p < 0.01), and markedly increased mean MSNA (76 +/- 5 vs 29 +/- 2 bursts per minute; p < 0.001). Atrial septostomy decreased mean SaO2 (to 85 +/- 2%; p < 0.001) and mean MSNA (to 69 +/- 4 bursts per minute; p < 0.01), but did not affect HR or BP. Therapy with supplemental O2 did not affect MSNA, BP, or HR. The decrease in MSNA was correlated to the decrease in right atrial pressure (r = 0.62; p < 0.05). CONCLUSIONS: Atrial septostomy in PAH patients decreases sympathetic hyperactivity despite an associated decrease in arterial oxygenation, and this appears to be related to decreased right atrial distension.

Optimization of right ventricular lead position in cardiac resynchronisation therapy.

BACKGROUND: The benefit of biventricular pacing (BiV) may be substantially affected by optimal lead placement. AIM: To evaluate the importance of right ventricular (RV) lead positioning on clinical outcome of BiV. METHODS AND RESULTS: A total of 99 patients with symptomatic heart failure and implantation of BiV system were included. Position of the left-ventricular (LV) lead was selected based on timing of local endocardial signal within the terminal portion of the QRS complex. RV lead was preferably positioned at the midseptum (n=74, RVS group) where the earliest RV endocardial signal was recorded. A subgroup of patients had RV lead placed in the apex (n=25, RVA group). NYHA class, maximum oxygen-uptake (VO(2)max), LV end-diastolic diameter (LVEDD, mm) and ejection fraction were assessed every third month. A trend towards greater improvement in NYHA class and significant increase in VO(2)max was present in the RVS group. Moreover, a significant decrease in LVEDD (DeltaLVEDD) was observed in the RVS group only (-3.4+/-6.5 mm versus +1.7+/-6.4 mm in RVA group at 12 months, p=0.004). No significant correlation between the degree of DeltaLVEDD and QRS narrowing induced by BiV was found. LVEDD reduction was predominantly present in dilated cardiomyopathy. CONCLUSIONS: Midseptal positioning of the RV lead appears to promote reverse LV remodelling during cardiac resynchronisation therapy.

Cryoablation for accessory pathways located near normal conduction tissues or within the coronary venous system in children and young adults.

BACKGROUND: Cryoablation may offer advantages over radiofrequency (RF) ablation for certain arrhythmia substrates, such as septal accessory pathways (APs). Data for young patients, especially regarding recurrence risk, require expansion. OBJECTIVES: The purpose of this study was to study institutional outcomes for cryoablation of APs located in potentially difficult septal regions for children and young adults. METHODS: Cryoablation was attempted in 35 young patients (mean age 15.6 years) with 37 APs that were either close to normal conduction tissues or inside the coronary venous system. Outcomes were compared with previously published institutional data for RF ablation at these same locations. RESULTS: Acute cryoablation success was achieved for 29 (78%) of 37 APs. Apart from permanent PR prolongation in one case and right bundle branch block in one other, there were no detrimental effects on normal conduction. At median follow-up of 207 days (range 2-695 days), AP conduction recurred for 13 (45%) of 29 ablated APs. Younger patient age and midseptal AP location correlated with higher likelihood of recurrence. Acute success rates for cryoablation were similar to RF ablation in our laboratory, but recurrence rates were significantly higher (P <.001). CONCLUSION: Cryoablation yields acute success rates comparable with RF ablation for difficult septal APs in young patients. The risk of AP recurrence appears higher after cryoablation, although safety benefits may provide suitable compensation for this deficiency. Methods for creating more effective cryoablation lesions need to be explored.

Paraseptal accessory pathway in Wolff-Parkinson- White-Syndrom: ablation from the right, from the left or within the coronary sinus/middle cardiac vein?

AIMS: In 1999 the consensus statement "living anatomy of the atrioventricular junctions" was published. With that new nomenclature the former posteroseptal accessory pathway (APs) are termed paraseptal APs. The aim of this study was to identify ECG features of manifest APs located in this complex paraseptal space. METHODS AND RESULTS: ECG characteristics of all patients who underwent radiofrequency ablation of an AP during a 3 year period were analyzed. Of the 239 patients with one or more APs, 30 patients had a paraseptal AP with preexcitation. Compared to APs within the coronary sinus (CS) or the middle cardiac vein (MCV) the right sided paraseptal APs significantly more often showed an isoelectric delta wave in lead II and/or a negative delta wave in aVR. The left sided paraseptal APs presented a negative delta wave in II significantly more often compared to the right sided APs. CONCLUSIONS: According to the site of radiofrequency ablation, paraseptal APs are classified into 4 subgroups: paraseptal right, paraseptal left, inside the CS or inside the MCV. Subtle differences in preexcitation patterns of the delta wave as well as of the QRS complex exist. However, the definitive localization of APs remains reserved to the periinterventional intracardiac electrogram analysis.

Regional cardiac sympathetic denervation and systolic compression of a septal perforator branch in a sudden death survivor with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is a heterogeneous primary cardiac disease with a broad clinical spectrum, including a high risk for sudden death in a certain subgroup of patients. However, the precise criteria for identifying the subgroup at high risk have not been established. The authors describe a 41-year-old man with hypertrophic cardiomyopathy who was examined after an episode of aborted sudden death. Extensive invasive and noninvasive investigations did not reveal a cardiac abnormality other than severe sympathetic denervation in the midbasal septal wall on iodine-123 MIBG SPECT imaging and concentric left ventricular hypertrophy on echocardiography. A retrospective review of the cardiac catheterization findings, however, revealed systolic compression of a septal perforator artery. The aborted sudden death of the patient was most likely associated with systolic compression of a septal branch or sympathetic denervation, which may have precipitated a ventricular arrhythmia in this patient.

Differentiation of atypical atrioventricular node re-entrant tachycardia from orthodromic reciprocating tachycardia using a septal accessory pathway by the response to ventricular pacing.

OBJECTIVES: The purpose of this study was to determine whether the response to ventricular pacing during tachycardia is useful for differentiating atypical atrioventricular node re-entrant tachycardia (AVNRT) from orthodromic reciprocating tachycardia (ORT) using a septal accessory pathway. BACKGROUND: Although it is usually possible to differentiate atypical AVNRT from ORT using a septal accessory pathway, a definitive diagnosis is occasionally elusive. METHODS: In 30 patients with atypical AVNRT and 44 patients with ORT using a septal accessory pathway, the right ventricle was paced at a cycle length 10 to 40 ms shorter than the tachycardia cycle length (TCL). The ventriculo-atrial (VA) interval and TCL were measured just before pacing. The interval between the last pacing stimulus and the last entrained atrial depolarization (stimulus-atrial [S-A] interval) and the post-pacing interval (PPI) at the right ventricular apex were measured on cessation of ventricular pacing. RESULTS: All 30 patients with atypical AVNRT and none of the 44 patients with ORT using a septal accessory pathway had an S-A-VA interval >85 ms and PPI-TCL >115 ms. CONCLUSIONS: The S-A-VA interval and PPI-TCL are useful in distinguishing atypical AVNRT from ORT using a septal accessory pathway.

[Cardioinhibitory vagal response not related to pain, and induced by radiofrequency application during ablation of right posteroseptal accessory pathway]. / Respuesta vagal cardioinhibidora, no mediada por dolor, secundaria a la aplicación de radiofrecuencia durante la ablación de una vía accesoria posteroseptal derecha.

Inappropriate sinus tachycardia is the most common arrhythmia induced by radiofrequency energy delivery in the posteroseptal area. It has been suggested that this could be secondary to parasymphathetic nerve injury. We report a patient with extreme sinus bradycardia and PR interval prolongation induced by radiofrequency energy delivered in the coronary sinus ostium area, but not related to any other stimulus. The most probable mechanism of the disorder was transient stimulation of the vagal afferent nerve fibers located in this anatomical area.

Spatial distribution and frequency dependence of arrhythmogenic vagal effects in canine atria.

INTRODUCTION: Prior studies in isolated canine atria demonstrated that acetylcholine-induced reentrant atrial fibrillation (AF) was triggered by multifocal activity in the area of normal impulse origin (sinus node-crista terminalis). The aim of this study was to investigate the activation sequence in AF induced by vagal stimulation (VS) in intact dog hearts. METHODS AND RESULTS: VS (10 to 50 Hz, 1 msec, 15 V, 5-sec trains) induced single or multiple atrial premature depolarizations (APDs), and/or AF in 8 of 10 open chest dogs. Occurrence of APDs and AF increased with increasing VS intensity. Epicardial mapping (254 unipolar electrodes) of both atria showed that APDs as a rule emerged from ectopic sites, often from the right atrial appendage. Activation mapping of the first 10 cycles of AF showed that only a small number (<3 to 4) of unstable reentrant circuits were possible at the same moment. Moreover, most sustained VS-induced AFs were accounted for by a single leading stable reentrant circuit that activated the remainder of the atria. CONCLUSION: (1) Occurrence of vagally induced APDs and AF increases with increasing frequency of VS. (2) VS-induced focal ectopic APDs are widely distributed over the atria. (3) A single APD can be sufficient for initiation of reentrant AF. (4) Despite its high rate of sustained AF, it may be maintained by single stable reentrant circuit. (5) The atrial septum can play an important role in both the initiation and the maintenance of VS-induced AF.

Bundle branch reentrant ventricular tachycardia with two distinct components of QRS complex due to simultaneous dual transseptal conduction.

We report the case of a patient with bundle branch reentrant ventricular tachycardia having two distinct components of the QRS complex due to simultaneous dual transseptal conduction. The macroreentrant circuit consisted of anterograde conduction down the left bundle branch and retrograde conduction up the right bundle branch. Extensively injured myocardium in the interventricular septum isolated the two separate transseptal passages, which exhibited a "fast" and "slow" conduction property, respectively. The QRS configuration resulted from a wavefront propagating from the left bundle branch via "fast" transseptal conduction, followed by another more delayed wavefront propagating via "slow" transseptal conduction, which played an important role in determining this unique QRS morphology.

Cardiac sympathetic activity in the asymmetrically hypertrophied septum in patients with hypertension or hypertrophic cardiomyopathy.

BACKGROUND: In patients with essential hypertension (HT), proportional (symmetric) left ventricular hypertrophy (LVH) is common. In contrast, hypertrophic cardiomyopathy (HCM) is characterized by disproportional LVH and, in particular, asymmetric septal hypertrophy (ASH); however, some hypertensive patients also develop ASH. It has not been determined whether such cases represent a distinct type of hypertensive LVH or HCM combined with hypertension. HYPOTHESIS: The study was undertaken to evaluate sympathetic activity in the interventricular septum in patients with HT and ASH or in patients with HCM. METHODS: The patients were evaluated by I-123 meta-iodobenzylguanidine (MIBG) and thallium-201 (201Tl) single-photon emission computed tomography (SPECT), respectively. They were divided into three groups: patients with essential HT and symmetric septal hypertrophy (Group A), patients with HT and ASH (Group B), and patients with HCM and ASH (Group C). RESULTS: Compared with the lateral wall, early uptake of MIBG in the septum was significantly higher in Group B than in Group A, but not significantly different between Groups A and C. Compared with the lateral wall, early uptake of 201Tl in the septum did not differ among the three groups. No significant difference in the MIBG clearance in the lateral wall was seen among the three groups. By contrast, MIBG clearances in the septum and apex were significantly greater in Group C than in Groups A and B. There was an inverse correlation between systolic thickening and MIBG clearance in the septum. CONCLUSION: These findings suggest that sympathetic activity in the septum differs between patients with HT and ASH and patients with HCM.

Quantitative studies on myelinated and unmyelinated nerve fibres in the interatrial septal region of aged rat hearts.

Intracardiac nerve fibres from the interatrial septum were studied quantitatively and qualitatively by electron microscopy of transversely sectioned nerve bundles in male Wistar rats of 4 and 24 months. No significant changes were found in the myelinated fibre diameters, myelinated axon diameters, myelin sheath thicknesses, g ratios, myelinated fibre areas, unmyelinated axon diameters and unmyelinated axon areas. However, there was evidence of structural changes to the nerve fibres and Schwann cells at 4 and 24 months, increasing in prevalence with age: some myelinated fibres showed infolds, disruptions and clefts of the myelin sheath and accumulation of electron dense myelin-like fragments in the axoplasm. Unmyelinated axons showed fewer changes in structure but also contained similar fragments in the axoplasm. The numbers of neurotubules and neurofilaments per microm2 in unmyelinated intracardiac axons was significantly greater than in those in samples of the cervical vagal trunk. This may be an adaptation to the continuous mechanical stress experienced by these intracardiac nerves. It is concluded that there is little structural evidence to suggest that the conductive properties of intracardiac nerve fibres are adversely affected in aged rats.

Cardiac afferents to the nucleus of the tractus solitarius: A WGA-HRP study in the rat.

Central distribution of the sensory fibers of the heart was investigated in the rat by the use of transganglionic transport of horseradish peroxidase (HRP). After the left intercostal thoracotomy was done under deep anesthesia and artificial respiration, wheat germ agglutinin-conjugated HRP (WGA-HRP) was injected into the left and right ventricular walls and the apex of the heart. HRP-labeled fibers were observed to be distributed to the dorsomedial portion of the medulla oblongata through the vagal nerve. The labeled fibers were present in various subnuclei of the nucleus of the tractus solitarius (NTS) bilaterally at the level of +0.36 to -1.74 mm to the obex. However, the most conspicuous feature in the present study was that the labeled fibers were exclusively confined to the medial, ventrolateral and commissural NTS with some distribution to the dorsolateral NTS. Although the labeling in the medial and ventrolateral NTS was observed to extend rostrocaudally, it was of interest that the labeling in the medial NTS was divided into the ventral and dorsal parts at the level around the obex. Accumulation of the labeled fibers in the commissural NTS was found at the level caudal to the obex and these fibers were traced to the caudal portion of its subnucleus with a gradual decrease in number. This pattern of distribution of cardiac afferents in the NTS was considered to be peculiar to the rat, because it was quite different from that reported previously in the cat.

Localization of precise origin of idiopathic ventricular tachycardia from the right ventricular outflow tract by a 12-lead ECG: a study of pace mapping using a multielectrode "basket" catheter.

Radiofrequency catheter ablation guided by pace-mapping techniques has proven effective in eliminating idiopathic ventricular tachycardia (VT) originating from the right ventricular outflow tract (RVOT). A method for rapidly identifying the origin of VT from 12-lead electrocardiogram (ECG) findings would be helpful for the catheter ablation procedure. The purpose of this study is to precisely localize the origin of idiopathic VT from the RVOT by a 12-lead ECG from a study of multipoint pace mapping. In one patient with premature ventricular complex (PVC) and 3 with VT, a "basket" catheter was deployed in the RVOT for bipolar pacing from 56 sites in the endocardium of RVOT. Under fluoroscopy the pacing sites were classified into the septum and free wall. We investigated the QRS morphology in leads, I, II, and III; the depth of the QS wave in leads aVR and aVL; and the height of the initial r wave in leads V1 and V2. Pacing was captured in 30-47 of 56 sites (54%-84%). As the pacing sites changed from the anterior to posterior of the septum, the QS notch (-) type in lead I shifted through rs to R, while a shift from R type to rR' or Rr' was noted in leads II and III. As the pacing sites changed from the anterior to posterior of the free wall, lead I showed a shift from the QS notch (+) type to R, while a shift from rR' to Rr' (or rR' unchanged) was found in leads II and III. The depth of the QS wave in leads aVR and aVL showed a tendency for aVR to be deeper than aVL toward the posterolateral attachment of both the septum and free wall, whereas aVL tended to be deeper than aVR toward the anterior attachment. The initial r waves in V1 and V2 became greater as the pacing site was positioned at a higher or more posterior location. These findings may provide more precise and clinically useful diagnostic information on the site of the origin of idiopathic VT originating from the RVOT by a 12-lead ECG.

Long-term follow-up in patients with the permanent form of junctional reciprocating tachycardia treated with radiofrequency ablation.

This study sought to determine the long-term follow-up, safety, and efficacy of radiofrequency catheter ablation of patients with the permanent form of junctional reciprocating tachycardia (PJRT). We assessed the reversibility of tachycardia induced LV dysfunction and we detailed the location and electrophysiological characteristics of these retrograde atrioventricular decremental pathways. PJRT is an infrequent form of reciprocating tachycardia, commonly incessant, and usually drug refractory. The ECG hallmarks include an RP interval > PR with inverted P waves in leads II, III, a VF, and V3-V6. During tachycardia, retrograde VA conduction occurs over an accessory pathway with slow and decremental conduction properties, located predominantly in the posteroseptal zone. It is known that long-lasting and incessant tachycardia may result in tachycardia induced severe ventricular dysfunction. We included 36 patients (13 men, 23 women, mean +/- SD, aged 44 +/- 22 years) with the diagnosis of PJRT. Seven patients had tachycardia induced left ventricular dysfunction. Radiofrequency energy was delivered at the site of earliest retrograde atrial activation during ventricular pacing or during reciprocating tachycardia. All patients were followed at the outpatient clinic and serial echocardiograms were performed in those who presented with depressed LV function. Radiofrequency ablation was performed in 36 decremental accessory pathways. Earliest retrograde atrial activation was right posteroseptal in 32 patients (88%), right mid-septal in 2 (6%), right posterolateral in 1 (3%), and left anterolateral in 1 (3%). Thirty-five accessory pathways were successfully ablated with a mean of 5 +/- 3 applications. A mid-septal accessory pathway could not be ablated. After a mean follow-up of 21 +/- 16 months (range 1-64) 34 patients are asymptomatic. There were recurrences in 8 patients after the initial successful ablation (mean of 1.2 months), 5 were ablated in a second ablation procedure, 2 patients required a third procedure, and 1 patient required four ablation sessions. All patients with LV dysfunction experienced a remarkable improvement after ablation. Mean preablation LV ejection fraction in patients with tachycardiomyopathy was 28% +/- 6% and rose to 51% +/- 16% after ablation (P < 0.02). Our study supports the concept that radiofrequency catheter ablation is a safe and effective treatment for patients with PJRT. Radiofrequency ablation should be the treatment of choice in these patients because this arrhythmia is usually drug refractory. The majority of accessory pathways are located in the posteroseptal zone. Cessation of the arrhythmia after successful ablation results in recovery of LV dysfunction.

Late complete atrioventricular block complicating radiofrequency catheter ablation of a left posteroseptal accessory pathway.

A patient with AV reentrant tachycardia underwent radiofrequency catheter ablation for interruption of a left posteroseptal accessory pathway (AP). During the RF current application, he developed transient complete left bundle branch block which lasted for 2 minutes. The following day the patient developed permanent complete AV block. This case indicates that great care should be taken when performing RF ablation for this AP site.