To study the spatial arrangement of the bundles of myocardial fibers presents in the left atrial-venous junctions and in the wall of the pulmonary veins.

Background Atrial fibrillation often occurs in the setting of hypertension and associated atrial dilation with pathologically increased cardiomyocyte stretch. In the setting of atrial dilation, mechanoelectric feedback has been linked to the development of ectopic beats that trigger paroxysmal atrial fibrillation mainly originating from pulmonary veins (PVs). However, the precise mechanisms remain poorly understood. Methods and Results We identify mechanosensitive, swelling-activated chloride ion channels (ICl,swell) as a crucial component of the caveolar mechanosensitive complex in rat and human cardiomyocytes. In vitro optical mapping of rat PV, single rat PV, and human cardiomyocyte patch clamp studies showed that stretch-induced activation of ICl,swell leads to membrane depolarization and decreased action potential amplitude, which trigger conduction discontinuities and both ectopic and reentrant activities within the PV. Reverse transcription quantitative polymerase chain reaction, immunofluorescence, and coimmunoprecipitation studies showed that ICl,swell likely consists of at least 2 components produced by mechanosensitive ClC-3 (chloride channel-3) and SWELL1 (also known as LRRC8A [leucine rich repeat containing protein 8A]) chloride channels, which form a macromolecular complex with caveolar scaffolding protein Cav3 (caveolin 3). Downregulation of Cav3 protein expression and disruption of caveolae structures during chronic hypertension in spontaneously hypertensive rats facilitates activation of ICl,swell and increases PV sensitivity to stretch 10- to 50-fold, promoting the development of atrial fibrillation. Conclusions Our findings identify caveolae-mediated activation of mechanosensitive ICl,swell as a critical cause of PV ectopic beats that can initiate atrial arrhythmias including atrial fibrillation. This mechanism is exacerbated in the setting of chronically elevated blood pressures.

Hydrogen sulphide (H2 S), one of the most common toxic air pollutants, is an important aetiology of atrial fibrillation (AF). Pulmonary veins (PVs) and left atrium (LA) are the most important AF trigger and substrate. We investigated whether H2 S may modulate the arrhythmogenesis of PVs and atria. Conventional microelectrodes and whole-cell patch clamp were performed in rabbit PV, sinoatrial node (SAN) or atrial cardiomyocytes before and after the perfusion of NaHS with or without chelerythrine (a selective PKC inhibitor), rottlerin (a specific PKC δ inhibitor) or KB-R7943 (a NCX inhibitor). NaHS reduced spontaneous beating rates, but increased the occurrences of delayed afterdepolarizations and burst firing in PVs and SANs. NaHS (100 μmol/L) increased IKATP and INCX in PV and LA cardiomyocytes, which were attenuated by chelerythrine (3 μmol/L). Chelerythrine, rottlerin (10 μmol/L) or KB-R7943 (10 μmol/L) attenuated the arrhythmogenic effects of NaHS on PVs or SANs. NaHS shortened the action potential duration in LA, but not in right atrium or in the presence of chelerythrine. NaHS increased PKC activity, but did not translocate PKC isoforms α, ε to membrane in LA. In conclusion, through protein kinase C signalling, H2 S increases PV and atrial arrhythmogenesis, which may contribute to air pollution-induced AF.

Cardiomyocytes in pulmonary veins (PVs) have been reported in rodents and humans. In humans they were related to atrial arrhythmias, including atrial fibrillation (AF). To investigate histological similarities and differences in PV cardiomyocyte localization and distribution, we performed comparative light and electron microscopic studies on humans, rats and mice, and generated a transgenic mouse strain. Results on mice (C57BL/6 and BALBc) and rats (Wistar) revealed that cardiomyocytes regularly extend from the hilus along venous vessels into the lung tissue surrounding individual intrapulmonary veins of varying diameters (70-250 microm). The cardiomyocytes showed the ultrastructure of a normal working myocardium with intact intercalated discs and tightly packed contractile filaments. In both lung and hilus cardiomyocytes were localized either close to the basal lamina of the endothelium or separated from it by smooth muscle cells and/or collagen fibres. In humans (autopsies, n=20) extrapericardiac cardiomyocytes were only found in 23 out of 78 veins and showed an incomplete sleeve at the lung hilus. In addition, cardiomyocytes occurred significantly more often in right than in left veins, however, never in intrapulmonary veins. We discuss the hypothesis that the variance in distribution of PV cardiomyocytes in humans and rodents might reflect the difference in pathogenesis and development of AF.

Pulmonary veins are involved in pathogenesis and treatment of atrial fibrillation and structures at risk during thoracic surgeries. There is lack of data regarding pulmonary vein morphology and morphometry in normal population.

Ablation of the pulmonary vein (PV) carina is occasionally required for PV isolation (PVI). Marshall bundle and epicardial connections between the right-sided PV (RtPV) carina and right atrium (RA) may be one of the mechanisms that necessitates carina ablation.

It is established that pulmonary vein isolation using the POLARx™ (Boston Scientific, Marlborough, MA, USA) cryoballoon is a rapid, safe, and effective approach. The new POLARx™ FIT (Boston Scientific), which is expandable from 28 to 31 mm in diameter, is currently available. However, there is limited evidence available regarding the treatment of atrial fibrillation in this setting. In this article, we report a case series of cryoballoon ablation in patients with atrial fibrillation using POLARx™ FIT.

Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory responses and structural alterations of the airways, lung parenchyma and pulmonary vasculature. Since Pentraxin-3 (PTX3) is a tuner of inflammatory responses and is produced by endothelial and inflammatory cells upon stimuli such as interleukin-1β (IL-1β), we hypothesized that PTX3 is involved in COPD pathogenesis.

Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare congenital malformation in neonates that results in severe respiratory distress and pulmonary hypertension. ACD/MPV is caused by mutations in the FOXF1 gene. Herein, a new case of a girl with ACD/MPV carrying a novel pathogenic variant of FOXF1 was reported.

Computed tomography angiography (CTA) or contrast-enhanced (CE) cardiovascular magnetic resonance angiography (CMRA) is often obtained in patients with atrial fibrillation undergoing evaluation prior to pulmonary vein (PV) isolation. Drawbacks of CTA include radiation exposure and potential risks from iodinated contrast agent administration. Free-breathing 3D balanced steady-state free precession (bSSFP) Non-contrast CMRA is a potential imaging option, but vascular detail can be suboptimal due to ghost artifacts and blurring that tend to occur with a Cartesian k-space trajectory or, in some cases, inconsistent respiratory gating. We therefore explored the potential utility of both breath-holding and free-breathing non-contrast CMRA, using radial k-space trajectories that are known to be less sensitive to flow and motion artifacts than Cartesian.

Diaspirin crosslinked hemoglobin (DCLHb) is a resuscitative fluid presently undergoing clinical trials. Administration of DCLHb is associated with an elevation of mean arterial pressure in vivo and contraction of isolated blood vessels in vitro. The mechanisms for the vascular actions are unknown but may be due to inhibition of nitric oxide (NO). Halothane has been reported to inhibit NO induced relaxation. We examined the effect of anesthetics on DCLHb induced contraction of blood vessels. Porcine pulmonary veins were excised, cut into rings and placed in organ chambers filled with 25 ml Krebs-Ringer solution (37 degrees C). Following equilibration at their optimal length the rings were exposed to increasing concentrations of serotonin(10(-8)M-10(-5)M). Endothelial activity was confirmed by relaxation greater than 80% with ACh (10(-6)M). DCLHb (1.5 x 10(-8)M to 6 x 10(-7)M) contracted porcine pulmonary veins (1.04 +/- 0.17g to 3.45 +/- 0.22g), and halothane (0.5% and 1%) significantly inhibited these DCLHb induced contractions in a dose-related manner (-41.6 +/- 8.1% and -73.3 +/- 8.2%, respectively). At equi-molar concentrations, isoflurane had no inhibitory activity. The relative effect of these volatile anesthetics is consistent with their inhibitory actions on other heme containing proteins. Propofol (10(-5)M) only has inhibitory effects on lower concentrations of DCLHb. Fentanyl did not have inhibitory effects. These results suggest that halogenated anesthetics may interact with the heme iron of DCLHb and inhibit its binding with NO.

Pulmonary veins (PV) are involved in the pathophysiology of paroxysmal atrial fibrillation. In the rat, left atrium (LA) and PV cardiomyocytes have different reactions to α1-adrenergic receptor activation. In freely beating atria-PV preparations, we found that electrical field potential (EFP) originated from the sino-atrial node propagated through the LA and the PV. The α1-adrenergic receptor agonist cirazoline induced a progressive loss of EFP conduction in the PV whereas it was maintained in the LA. This could be reproduced in preparations electrically paced at 5 Hz in LA. During pacing at 10 Hz in the PV where high firing rate ectopic foci can occur, cirazoline stopped EFP conduction from the PV to the LA, which allowed the sino-atrial node to resume its pace-making function. Loss of conduction in the PV was associated with depolarization of the diastolic membrane potential of PV cardiomyocytes. Adenosine, which reversed the cirazoline-induced depolarization of the diastolic membrane potential of PV cardiomyocytes, restored full over-shooting action potentials and EFP conduction in the PV. In conclusion, selective activation of α1-adrenergic receptors results in the abolition of electrical conduction within the PV. These results highlight a potentially novel pharmacological approach to treat paroxysmal atrial fibrillation by targeting directly the PV myocardium.

To describe disease course, histopathology, and outcomes for infants with atypical presentations of alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) who underwent bilateral lung transplantation.

Ectopic beats originating from the pulmonary vein (PV) trigger atrial fibrillation (AF). The purpose of this study was to clarify the electrophysiological determinant of AF initiation from the PVs.

1. The mechanisms by which histamine and 5-HT differentially contract pulmonary arteries and veins are unclear. In lung explants from 26 guinea-pigs, we compared responses of pulmonary arteries and vein to histamine, 5-HT and KCI, and examined potential determinants for the differential responses. Lungs were filled with agarose, sectioned into approximately 1 mm thick slices, and vascular luminal areas measured by image analysis. 2. Histamine and 5-HT produced a concentration-dependent constriction in arteries and veins, greater in the latter. KCl constricted arteries and veins equally. 3. The histamine H1 antagonist chlorpheniramine (10(-4) M) abolished contractions to histamine; the H2 antagonist cimetidine enhanced maximal responses and sensitivity of arteries and veins to histamine, and diminished the differences between their maximal responses; the NO synthase inhibitor Nomega-nitro-L-arginine (L-NOARG) increased the maximal responses of arteries and veins, and the differences between their responses; indomethacin had no effect. 4. Contractions to 5-HT were abolished in arteries and markedly reduced in veins by the 5-HT2 antagonist ketanserin (10(-4) M); L-NOARG potentiated the maximal responses of arteries but not of veins; indomethacin increased the maximal responses of arteries but reduced them in veins. 5. By morphometry, arteries had a greater medial thickness and luminal diameter than veins. 6. The data suggest that in guinea-pigs, H2 receptors are responsible for the differential contractile responses of pulmonary arteries and veins to histamine, whereas endothelium-derived vasoactive substances are responsible for their differential contractile responses to 5-HT.

RECOVER AF evaluated the performance of whole-chamber non-contact charge-density mapping to guide the ablation of non-pulmonary vein (PV) targets in persistent atrial fibrillation (AF) patients following either a first or second failed procedure.

Platelet-derived growth factor (PDGF)-BB and its receptor PDGFR are highly expressed in pulmonary hypertension (PH) and mediate proliferation. Recently, we showed that PDGF-BB contracts pulmonary veins (PVs) and that this contraction is prevented by inhibition of PDGFR-β (imatinib/SU6668). Here, we studied PDGF-BB-induced contraction and downstream-signalling in isolated perfused lungs (IPL) and precision-cut lung slices (PCLS) of guinea pigs (GPs).

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare and fatal disorder that occurs in the developing fetal lungs; at birth, infants exhibit an oxygenation disorder accompanied by severe pulmonary hypertension (PH) and have a very short life span. ACDMPV is definitively diagnosed by pathological findings, and infants born with unexplained severe PH may not be properly diagnosed without a biopsy or autopsy.

A direct comparison of three-dimensional transesophageal echocardiography (3DTEE) and cardiac computed tomography imaging has demonstrated good inter-technique agreement for the following pulmonary vein (PV) parameters: the ostium area of the right superior PV (RSPV) and its major (a) and minor axis (b) diameters, the left lateral ridge and the minor axis (b) diameter of the left superior PV. Herein, under investigation, was the predictive value of these parameters for arrhythmia recurrence (AR) after PV isolation with the 28 mm second generation cryoballoon (CBG2).

Inflammation, oxidative stress, myocardial injury biomarkers and clinical parameters (longer AF duration, left atrial enlargement, the metabolic syndrome) are factors commonly related to AF recurrence. This study aims to assess the predictive value of laboratory and clinical parameters responsible for early recurrence of atrial fibrillation (ERAF) following cryoballoon ablation (CBA) using statistical assessment and machine learning algorithms. This study group comprised 118 consecutive patients (mean age, 62.5 ± 7.8 years; women 36%) with paroxysmal (54.1%) and persistent (45.9%) AF who underwent their first pulmonary vein isolation (PVI) performed by CBA (Arctic Front Advance 2nd generation 28 mm). The biomarker concentrations were measured at baseline and after CBA in a 24-h follow-up. ERAF was defined as at least a 30-s episode of arrhythmia registered by a 24 h-Holter monitor within the 3 months following the procedure. 56 clinical, laboratory and procedural variables were collected from each patient. We used two classification algorithms: support vector machines, gradient boosted tree. The synthetic minority over-sampling technique (SMOTE) was used to provide a balanced training data set. Within a period of 3 months 21 patients (17.8%) experienced ERAF. The statistical analysis indicated that the lowered levels of post-ablation TnT (p = 0.043) and CK-MB (p = 0.010) with the TnT elevation (p = 0.044) were the predictors of ERAF following CBA. In addition, diabetes and statin treatment were significantly associated with ERAF after CBA (p < 0.05). The machine learning algorithms confirmed the results obtained in the univariate analysis.