Congenital heart block: evidence for a pathogenic role of maternal autoantibodies

During pregnancy in autoimmune conditions, maternal autoantibodies are transported across the placenta and may affect the developing fetus. Congenital heart block (CHB) is known to associate with the presence of anti-Ro/SSA and anti-La/SSB antibodies in the mother and is characterized by a block in signal conduction at the atrioventricular (AV) node. The mortality rate of affected infants is 15% to 30%, and most live-born children require lifelong pacemaker implantation. Despite a well-recognized association with maternal anti-Ro/La antibodies, CHB develops in only 1% to 2% of anti-Ro-positive pregnancies, indicating that other factors are important for establishment of the block. The molecular mechanisms leading to complete AV block are still unclear, and the existing hypotheses fail to explain all aspects of CHB in one comprehensive model. In this review, we discuss the different specificities of maternal autoantibodies that have been implicated in CHB as well as the molecular mechanisms that have been suggested to operate, focusing on the evidence supporting a direct pathogenic role of maternal antibodies. Autoantibodies targeting the 52-kDa component of the Ro antigen remain the antibodies most closely associated with CHB. In vitro experiments and animal models of CHB also point to a major role for anti-Ro52 antibodies in CHB pathogenesis and suggest that these antibodies may directly affect calcium regulation in the fetal heart, leading to disturbances in signal conduction or electrogenesis or both. In addition, maternal antibody deposits are found in the heart of fetuses dying of CHB and are thought to contribute to an inflammatory reaction that eventually induces fibrosis and calcification of the AV node, leading to a complete block. Considering that CHB has a recurrence rate of 12% to 20% despite persisting maternal autoantibodies, it has long been clear that maternal autoantibodies are not sufficient for the establishment of a complete CHB, and efforts have been made to identify additional risk factors for this disorder. Therefore, recent studies looking at the influence of genetic and environmental factors will also be discussed.Autoantibody-associated congenital heart block (CHB) is a passively acquired autoimmune condition in which maternal autoantibodies are thought to initiate conduction disturbances in the developing fetal heart. Hallmarks of autoantibody-associated CHB are the presence of immune complex deposits, inflammation, calcification, and fibrosis in the fetal heart and a block in signal conduction at the atrioventricular (AV) node in an otherwise structurally normal heart. Clinical signs most commonly develop during weeks 18 to 24 of pregnancy. Although autoantibody-associated CHB may initially be detected as a first- or second-degree AV block, most of the affected pregnancies will present with fetal bradycardia in third-degree (complete) AV block, and ventricular rates typically are between 50 and 70 beats per minute. A complete AV block is a potentially lethal condition associated with significant morbidity, and the majority of affected children require permanent pacemaker implantation [1-3].Whereas complete AV block is the major manifestation of autoantibody-associated CHB, other cardiac abnormalities are increasingly being recognized. Transient first-degree AV block has been shown to occur in up to 30% of fetuses of mothers with anti-SSA/Ro 52-kDa antibodies [4]. The presence of sinus bradycardia [5-7] and prolongation of the QTc interval [8,9] have also been reported; however, these findings were not replicated in another recent study [10]. Endocardial fibroelastosis and cardiomyopathy have been reported in both the presence and absence of conduction abnormalities and are associated with a poor prognosis [11-14].Since the initial observation that sera of mothers of children with CHB contain anti-SSA/Ro antibodies, the association between maternal autoantibodies and CHB has been extensively studied. Most of the current knowledge comes from the comparative analysis of sera of women with affected or healthy infants, and additional information has been generated through the use of animal models. Nevertheless, the pathogenic molecular mechanisms of autoantibody-associated CHB remain unclear. Because the risk for CHB in an anti-SSA/Ro-positive pregnancy is only 1% to 2% [5,15], the need for a better marker not only for pregnancies at risk but also for the identification of other risk factors influencing the development of CHB is still important. This review will give a broad perspective of the maternal antibodies that have been associated with CHB and then will focus on the antibody specificities that have been more specifically implicated in the pathogenesis of the disease through in vitro and in vivo studies. The current hypotheses for autoantibody-associated CHB development will be discussed with an emphasis on the potential molecular targets for maternal antibodies in the fetal heart before mentioning other risk factors that have recently come to light.     

A case of an acquired high-degree AV block in a pregnant woman

Acquired heart block during pregnancy is rare. We describe the case of a 29-year-old pregnant female with fatigue due to an unexplained high-degree AV conduction disorder. She was treated with a dual chamber pacing system. Further pregnancy and delivery were without complications. The sparse literature on this topic is reviewed. (Neth Heart J 2008;16:419-21.)     

News and Views

The aim of this study was to examine 24h patterning in the symptoms indicative of third-degree atrio-ventricular (AV) heart block. We found a total of 227 cases (126 men and 101 women) of third-degree AV block that had been diagnosed by the Emergency Medical Department of the St. Anna Hospital in Ferrara, Italy between 1990 and 2001. Determination of the hour of onset of symptomatic third-degree AV block, however, was possible and listed in the records of only 161 or 70.9% of the cases (92 men and 69 women). The onset time of every event was categorized into one of four 6h spans of the 24h: night (00:00–05:59h), morning (06:00–11:59h), afternoon (12:00–17:59h), and evening (18:00–23:59h). The onset of the symptoms of third-degree AV block in the sample of 161 cases was significantly greater in the morning between 06:00 and 11:59h than any other 6h span of the day and night (χ²-test; p<0.001). The same phenomenon was substantiated in the subgroup of the 92 males (χ²; p<0.0001), although it could not be detected for the smaller subgroup of 69 women. The 24h pattern, with morning preference, in the onset of symptomatic third-degree AV block is similar to the one in sudden cardiac death and cardiogenic cardiac arrest. The etiology of the 24h pattern in symptomatic AV block is unknown; it may be an expression of intrinsic biological rhythmicity within the heart tissue or its control system, and/or the timing of environmental triggers resulting in coronary ischemia.     

Microwave ablation of the atrioventricular junction in open-chest dogs

The use of microwave energy for ablation of the atrioventricular (AV) junction was examined in open-chest dogs. Using a specially designed microwave catheter and a 2450 MHz generator, microwave energy was delivered to the AV junction according to one of two protocols. In protocol 1, increasing amounts of energy were delivered until irreversible AV block occurred. In protocol 2, only two applications of energy were used, one at low energy and the other at an energy found to be high enough to cause irreversible AV block. Each dog received between one and six applications of microwave energy. The amount of energy delivered per application ranged from 25.6 to 311.4 J. No AV block was seen at 59.4 ± 28.3 J. Reversible AV block was seen with an energy of 120.6 ± 58 J. Irreversible AV block was seen at 188.1 ± 75.9 J. Irreversible AV block could be achieved in each animal. There was no difference in the energy required to cause irreversible AV block between the two protocols. The tissue temperature measured near the tip of the microwave catheter was correlated with both the amount of energy delivered and the extent of AV block caused. Histologic examination demonstrated coagulation necrosis of the conduction system. Microwave energy is a feasible alternative energy source for myocardial ablation. Since tissue damage is due exclusively to heating and the resulting rise in temperature can be measured, microwave energy may have advantages over currently existing energy sources in terms of both titrating delivered energy and monitoring the extent of tissue destruction. © 1995 Wiley-Liss, Inc.     

Morning preference in onset of symptomatic third-degree atrioventricular heart block

The aim of this study was to examine 24h patterning in the symptoms indicative of third-degree atrio-ventricular (AV) heart block. We found a total of 227 cases (126 men and 101 women) of third-degree AV block that had been diagnosed by the Emergency Medical Department of the St. Anna Hospital in Ferrara, Italy between 1990 and 2001. Determination of the hour of onset of symptomatic third-degree AV block, however, was possible and listed in the records of only 161 or 70.9% of the cases (92 men and 69 women). The onset time of every event was categorized into one of four 6h spans of the 24h: night (00:00-05:59h), morning (06:00-11:59h), afternoon (12:00-17:59h), and evening (18:00-23:59h). The onset of the symptoms of third-degree AV block in the sample of 161 cases was significantly greater in the morning between 06:00 and 11:59h than any other 6h span of the day and night (chi2-test; p < 0.001). The same phenomenon was substantiated in the subgroup of the 92 males (chi2; p < 0.0001), although it could not be detected for the smaller subgroup of 69 women. The 24h pattern, with morning preference, in the onset of symptomatic third-degree AV block is similar to the one in sudden cardiac death and cardiogenic cardiac arrest. The etiology of the 24h pattern in symptomatic AV block is unknown; it may be an expression of intrinsic biological rhythmicity within the heart tissue or its control system, and/or the timing of environmental triggers resulting in coronary ischemia.     

Ventriculo-atrial gradient due to first degree atrio-ventricular block: a case report

Background

Isolated, asymptomatic first degree AV block with narrow QRS has not prognostic significance and is not usually treated with pacemaker implantation. In some cases, yet, loss of AV synchrony because of a marked prolongation of the PR interval may cause important hemodynamic alterations, with subsequent symptoms of heart failure. Indeed, AV synchrony is crucial when atrial systole, the "atrial kick", contributes in a major way to left ventricular filling, as in case of reduced left ventricular compliance because of aging or concomitant structural heart disease.

Case presentation

We performed a trans-septal left atrium catheterization aimed at evaluating the entity of a mitral valve stenosis in a 72-year-old woman with a marked first-degree AV block, a known moderate aortic stenosis and NYHA class III symptoms of functional deterioration. We occurred in a deep alteration in cardiac hemodynamics consisting in an end-diastolic ventriculo-atrial gradient without any evidence of mitral stenosis. The patient had a substantial improvement in echocardiographic parameters and in her symptoms of heart failure after permanent pacemaker implantation with physiological AV delay.

Conclusion

We conclude that if a marked first degree AV block is associated to instrumental signs or symptoms of heart failure, the restoration of an optimal AV synchrony, achieved with dual-chamber pacing, may represent a reasonable therapeutic option leading to a consequent clinical improvement.     

Comparison of arrhythmia detection by conventional Holter and a novel ambulatory ECG system using patch and Android App,over 24 h period

BackgroundAmbulatory electrocardiogram (AECG) is done for evaluation of arrhythmia. Commonly used AECG system is 24 h Holter. Patch based second generation AECG monitoring devices, which can record for longer periods, are now available.ObjectiveAndroid App based WebCardio using WiPatch is a new AECG system which records ECG in two leads for 72 h. Our study compared the arrhythmia detection by WebCardio and conventional Holter by simultaneously connecting both for 24 h in patients having indication for AECG.MethodsThe AECG of patients who had simultaneous recording with WebCardio and conventional Holter, in the department of Cardiology, Medical College, Thrissur were evaluated. Ability to detect any of the 6 arrhythmias :1) atrial fibrillation (AF), 2) atrioventricular (AV) block, 3) sinus pause of ≥3 s (SP), 4) supraventricular tachycardia (SVT), 5) premature ventricular complex (PVC) and 6) ventricular tachycardia (VT)/ventricular fibrillation (VF) was compared. Detection of each arrhythmia was also compared.Results141 patients had simultaneous recordings by both systems of AECG. The WebCardio picked up at least one of the 6 arrhythmias; AF, AV block, SP, SVT, PVC or VT/VF in 98 cases compared to 88 in the Holter (McNemars test, two tail P = 0.006). In eleven cases WebCardio detected an arrhythmia where Holter could not. In one case Holter identified an arrhythmia and WebCardio could not. Individual arrhythmias; AF, SP, SVT and VT/VF were detected equally by both systems. AV block (23 Vs 18, p = 0.0625) and PVCs (83 Vs 74, p = 0.0636) were detected in more number of cases in WebCardio. In the five cases where WebCardio alone identified AV block, four had poor quality of P wave in the Holter.ConclusionArrhythmia was picked up in more number of patients by the WebCardio compared to Holter. This was due to higher pickup of AV block and PVCs by WebCardio. Difference in AV block identification was due to better quality of P in WebCardio. WebCardio is a good alternative to Holter for AECG.     

Relationship between hair elements and severity of atrioventricular block in horses

The aim of this study was to investigate the relationships between the mean concentrations of trace elements and the severity of the seconddegree atrioventricular (AV) block in the mane hair of horses. Electrocardiographs of horses were continually recorded for 6 h using a holter cardiac monitor to determine dropped ventricular beats (DVBs) which can be used as an indicator of the severity of the AV block. Mane hair Ca, Cu, Mg, and Zn concentrations were measured by the particle-induced X-ray emission method. The Zn/Cu ratio and Ca concentration in mane hair were significantly and positively correlated with the hourly DVBs in horse with a second-degree AV block (p<0.01, r2=0.485; p<0.05, r2=0.351, respectively). Proposed diagnostic cutoff points for hair Ca concentration and Zn/Cu ratio based on receiver operating characteristics curves analysis in detecting second-degree AV block were set at 1536 μg/g and 26.0, respectively. Those results with horse hair suggest that the evaluation of the Ca, Cu, Mg, and Zn status in mane hair by this method is strongly related to the severity of second-degree AV block and might predict the susceptibility of an individual much before the development of the symptom.     

Using long-term averted goats for selective grazing in olive groves

Conditioned taste aversion (CTA) is a useful tool to modify animal feed preferences, allowing the implementation of selective grazing to control weeds in tree orchards without damaging the trees or affecting fruit production. LiCl is commonly used for inducing CTA. However, studies investigating the long-term persistence of CTA by LiCl in small ruminants are scarce. With this aim, we evaluated the efficiency of two LiCl doses (AV1 and AV2, 175 and 200 mg/kg BW, respectively) and a control (C, 0 mg/kg BW) for averting non-lactating dairy goats (n=15) to olive tree leaves. Aversion induction was reinforced on day 9 in those goats that consumed >10 g of olive leaves. Mid-term aversion effectiveness was assessed by five double-choice feeding tests (days 16, 24, 31, 38 and 53) of 30 min each, where 100 g of olive leaves were offered side-by-side with 390 g of Italian rye-grass (as-fed). Long-term aversion effectiveness was assessed in C, AV1 and AV2 goats by grazing for 30 min in paddocks with a simulated olive tree (days 59, 90, 121, 182 and 420). Moreover, C and AV2 goats were compared under on-field conditions (days 143, 211 and 363) in a commercial olive grove also for 30 min. The CTA proved to be established with a single LiCl dose in all goats and persisted for 4 and 55 days in AV1 and AV2 goats, respectively (P<0.001). However, 80% AV1 and 20% AV2 goats needed to be reinforced at day 9. When grazing under simulated olive tree and commercial olive grove conditions, the CTA goats, especially AV2 group, avoided the contact with the olive trees and minimally used a bipedal stance to feed leaves, than control goats. On average, time proportion spent consuming olive leaves and sprouts was much greater (P<0.05) for C (50.7±9.1%) than for AV1 (14.4±3.9%) and AV2 (3.1±0.9%). In conclusion, the 200 mg LiCl/kg BW dose was more effective than the 175 mg LiCl/kg BW dose for inducing an effective long-term CTA to olive tree leaves in goats.     

A Novel Prokaryotic Promoter Identified in the Genome of Some Monopartite Begomoviruses

Geminiviruses are known to exhibit both prokaryotic and eukaryotic features in their genomes, with the ability to express their genes and even replicate in bacterial cells. We have demonstrated previously the existence of unit-length single-stranded circular DNAs of Ageratum yellow vein virus (AYVV, a species in the genus Begomovirus, family Geminiviridae) in Escherichia coli cells, which prompted our search for unknown prokaryotic functions in the begomovirus genomes. By using a promoter trapping strategy, we identified a novel prokaryotic promoter, designated AV3 promoter, in nts 762-831 of the AYVV genome. Activity assays revealed that the AV3 promoter is strong, unidirectional, and constitutive, with an endogenous downstream ribosome binding site and a translatable short open reading frame of eight amino acids. Sequence analyses suggested that the AV3 promoter might be a remnant of prokaryotic ancestors that could be related to certain promoters of bacteria from marine or freshwater environments. The discovery of the prokaryotic AV3 promoter provided further evidence for the prokaryotic origin in the evolutionary history of geminiviruses.     

Moving Domain Computational Fluid Dynamics to Interface with an Embryonic Model of Cardiac Morphogenesis

Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) and pressure gradients (∇P) across the atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP)^y1 transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD) model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV) across the atrioventricular (AV) canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf), simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6), whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis.     

BMP-2 Induces Versican and Hyaluronan That Contribute to Post-EMT AV Cushion Cell Migration

Distal outgrowth and maturation of mesenchymalized endocardial cushions are critical morphogenetic events during post-EMT atrioventricular (AV) valvuloseptal morphogenesis. We explored the role of BMP-2 in the regulation of valvulogenic extracellular matrix (ECM) components, versican and hyaluronan (HA), and cell migration during post-EMT AV cushion distal outgrowth/expansion. We observed intense staining of versican and HA in AV cushion mesenchyme from the early cushion expansion stage, Hamburger and Hamilton (HH) stage-17 to the cushion maturation stage, HH stage-29 in the chick. Based on this expression pattern we examined the role of BMP-2 in regulating versican and HA using 3D AV cushion mesenchymal cell (CMC) aggregate cultures on hydrated collagen gels. BMP-2 induced versican expression and HA deposition as well as mRNA expression of versican and Has2 by CMCs in a dose dependent manner. Noggin, an antagonist of BMP, abolished BMP-2-induced versican and HA as well as mRNA expression of versican and Has2. We further examined whether BMP-2-promoted cell migration was associated with expression of versican and HA. BMP-2- promoted cell migration was significantly impaired by treatments with versican siRNA and HA oligomer. In conclusion, we provide evidence that BMP-2 induces expression of versican and HA by AV CMCs and that these ECM components contribute to BMP-2-induced CMC migration, indicating critical roles for BMP-2 in distal outgrowth/expansion of mesenchymalized AV cushions.     

Bioprospecting of Amazon soil fungi with the potential for pigment production

The aim of this study was to isolate fungi able to produce pigments. Fifty strains were isolated from the Amazon soil by the conventional technique of serial dilution. Submerged fermentation was performed in Czapeck broth in order to select strains able to synthesise pigments. Five strains were able to produce pigments and were identified by sequencing the rDNA (ITS regions). These fungi were identified as Penicillium sclerotiorum 2AV2, Penicillium sclerotiorum 2AV6, Aspergillus calidoustus 4BV13, Penicillium citrinum 2AV18 and Penicillium purpurogenum 2BV41. P. sclerotiorum 2AV2 produced intensely coloured pigments and were therefore selected for chemical characterisation. NMR identified the pigment as sclerotiorin. In this work, the influence of nutrients on sclerotiorin yield was also studied and it was verified that rhamnose and peptone increased production when used separately. These results indicate that Amazonian fungi bioprospecting is a viable means to search for new sources of natural dyes.     

Left Ventricular Dysfunction Caused by Unrecognized Surgical AV block in a Patient with a Manifest Right Free Wall Accessory Pathway

A 24-year-old male with Wolff-Parkinson-White syndrome developed systolic cardiomyopathy and severe heart failure following membranous ventricular septal defect repair and tricuspid valve replacement. Following successful catheter ablation of a right anterolateral accessory pathway (AP), complete AV block with junctional escape rhythm was noted. Patient subsequently underwent implantation of a biventricular ICD. Heart failure symptoms significantly improved soon after and left ventricular systolic function normalized 3 months post-procedure. In this case, surgically acquired AV block likely explains development of postoperative cardiomyopathy by facilitating ventricular activation solely via the AP and thereby increasing the degree of ventricular dyssynchrony.     

Development of a model of complete heart block in rats

Atrioventricular(AV) block is a useful substrate for the study of cardiacphysiology. The objective of this investigation was todevelop a straightforward and reproducible model of permanent AV blockin rats. Working through a sternotomy, we used an epicardial fat padbetween the aortic root and the right atrial wall of the rat as alandmark for the site for injection of 70% ethanol (5-10 µl)into the myocardium 3 mm below the epicardial surface. Stable, completeheart block was produced in 23 of 28 rats (82%) with a success rate of100% in the last 16 rats of the series. Saline injection produced noheart block in 15 rats. A separate group of 14 animals was allowed torecover. Chronic heart block was achieved in all ethanol-injectedanimals for up to 7 days before death. The survival rate in therecovered rats was 90% in the ethanol-injected group and 100% in thesaline-injected control group. Acute hemodynamic changes following theproduction of heart block consisted of an increase in central venouspressure, a decrease in systolic blood pressure, a decrease in leftventricular pressure, and a decrease in change in pressure overtime. Chronic hemodynamic changes demonstrated a return tobaseline of the central venous pressure, a persistent decrease insystolic blood pressure, and a decrease in left ventricular pressure.After the rats were killed and the hearts were dissected, discreteareas of myocardial damage were identified histologically in the atrialseptum near the AV conduction axis tissue in the ethanol-injectedhearts. Complete heart block was associated only with lesions extendinginto the specialized muscle of the AV node or His bundle. Focal mildhemorrhage, inflammation, and damaged myocardial fibers were observedin the acute stage, whereas healing lesions were characterized bygranulation tissue and fibrosis replacing conduction tissue. The simpletechnique described provides a reproducible model for permanent,complete heart block and the study of cardiac function.

     

Habitat preferences of aphidophagous coccinellids [Coleoptera]

From May to July 1982 and 1983, coccinellids were sampled in habitats that differed in aphid density, insolation, and host plant type. The number of adults ofCoccinella 7-punctata (CS),C. 5-punctata (CQ),Propylea 14-punctata (PQ),Adonia variegata (AV),Adalia bipunctata (AB),A. 10-punctata (AD), andCalvia 14-guttata (CA) were recorded. AB, AV and CS preferred high, while CQ tolerated low aphid density. CQ, CS, AB and AV preferred sunny, while AD and CA tolerated shaded conditions. CS and AV preferred herbaceous plants, AD and CA large plants, particularly trees, AB showed little specialization, CQ preferred trees early in the season and sparse herbaceous plants later. PQ appeared to be a generalist with a wide tolerance of all these factors, but with a tendency to move from trees to herbaceous plants as the season progressed. Habitats with a high abundance of a species were assumed to be those with on optimum combination of the preferred conditions. There were slight differences in the breadth of habitat preferences, and a little habitat overlap between species. The tendency to aggregate was greater in AB than in other species. Annual variations in species abundance influenced the number of habitats occupied, but not the abundance in the favoured places.     

Toward predicting Dinophysis blooms off NW Iberia: A decade of events

Dinophysis acuminata and Dinophysis acuta are recurrent species off NW Iberia but their outbreaks occur under different conditions. A decade (2004–2013) of weekly data for each species at two sentinel stations located at the entrance of Rias de Aveiro-AV (NW Portugal, 40°38.6′ N) and Pontevedra-PO (Galicia, Spain, 42°21.5′ N), were used to investigate the regional synchronism and mesoscale differences related to species detection, bloom (>200 cells L⁻¹) initiation and development. Results highlight the high interannual variability of bloom events and summarize the associated meteorological/oceanographic conditions. D. acuta blooms were observed in 2004–2008 and 2013, and the species highest maxima at AV occurred after the highest maxima of its prey Mesodinium, with a time-lag of 2–3 weeks. D. acuminata blooms were observed every year at both stations. The cell concentration time series shows that the blooms generally present a sequence starting in March with D. acuminata in PO and three weeks later in AV, followed by D. acuta that starts at AV and three months later in PO. Exceptionally, D. acuminata blooms occurred earlier at AV than PO, namely in high spring upwelling (2007) or river runoff (2010) years. A four-year gap (2009–2012) of D. acuta blooms occurred after an anomalous 2008 autumn with intense upwelling which is interpreted as the result of an equatorward displacement of the population core. Numerical model solutions are used to analyze monthly alongshore current anomalies and test transport hypotheses for selected events. The results show a strong interannual variability in the poleward/equatorward currents associated with changes in upwelling forcing winds, the advection of D. acuta blooms from AV to PO and the possibility that D. acuminata blooms at AV might result from inocula advected southward from PO. However, the sensitivity of the results to vertical position of the lagrangian tracers call for more studies on species distribution at the various bloom stages.     

Control of cell migration in atrioventricular pads during chick early heart development: Analysis of cushion tissue migration in vitro

The formation of the valvular and septal primordia of the embryonic heart depends upon the migration of endocardial cushion tissue mesenchyme (CT) to populate the cardiac jelly (CJ) in specific heart regions (e.g., atrioventricular (AV) pads). It has been proposed that the migration of CT may be directed by macromolecules of the CJ. In this study, [³H]thymidine-labeled endocardial (EC) and CT cells were transplanted onto intact pre- and postmigratory AV pads in vitro to test whether the compositional or structural changes known to occur in the cardiac jelly during development influence the migration of cushion tissue cells. After transplantation of labeled donor cells, host AV pads were fixed, embedded, and sectioned, and autoradiography was performed to determine the distribution of labeled donor cells within the host CJ. The experiments indicate that transplanted mural EC cells remain primarily at the AV pad surface, while grafted CT cells of all developmental ages rapidly invade both developmentally young and older AV pads. Furthermore, CT cells readily migrate in a direction opposite to that of cells in vivo when transplanted to inverted AV pads from which the myocardium has been removed. It is concluded that the CJ matrix, which is clearly a suitable framework for CT cell migration, provides no direct cues to determining the polarity or extent of migration.