Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts

OBJECTIVE: Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic changes during regional ischemia in hearts from pigs fed a diet rich in fish oil. METHODS: Pigs received diets rich in fish oil, in sunflower oil, or a control diet for 8 weeks. Hearts were isolated and perfused. Ischemia was created by occluding the left anterior descending artery. Diastolic stimulation threshold, refractory period, conduction velocity, activation recovery intervals and the maximum downstroke velocity of 176 electrograms were measured in the ischemic zone. Spontaneous arrhythmias during 75 min of regional ischemia were counted. RESULTS: More episodes of spontaneous ischemia-induced sustained ventricular tachycardia and ventricular fibrillation occurred in the fish oil and sunflower oil group than in the control group. More inexcitable myocardium was present in the ischemic zone in the group fed fish oil or sunflower oil than in the control group after 20 min of ischemia. After 40 min of ischemia, more block occurred in the control group than in the other groups. The downstroke velocity of the electrograms in the ischemic border zone was lower in the fish oil group and sunflower oil group than in the control after 20 min. CONCLUSIONS: A diet rich in fish oil results in proarrhythmia compared to a control diet during regional ischemia in pigs. Myocardial excitability is reduced in the fish oil and sunflower oil group during the early phase of arrhythmogenesis. In the late phase of arrhythmogenesis, excitability is more reduced in the control group than in the fish oil and sunflower oil group.     

Augmented mandibular bone structurally adapts to functional loading

Long-term changes in trabecular bone structure during the 10 years following onlay grafting with simultaneous mandibular implant placement were studied. Extraoral radiographs of both mandibular sides in eight patients were taken regularly. Bone structure was analysed using a custom-written image analysis program. Parameters studied were trabecular area and perimeter and marrow cavity area and perimeter. After skeletonisation of the trabecular network, the number of end points and branching points, skeleton length, and branch angle were determined. The observed structural changes agree with the development of a more complex and more delicate or fine osseous structure. The bone shows more trabecular branching. All changes are most pronounced in the graft spongiosa, but are also found in the graft cortex and in the original mandible. The mean trabecular branch angle becomes more horizontal. The applied technique can be used to analyse long-term changes in the architecture of bone grafts. Changes found in the graft architecture correspond to changes expected after functional adaptation to loading.     

Role of immune interferon in the monocytic differentiation of human promyelocytic cell lines induced by leukocyte conditioned medium

Conditioned medium (CM) from lectin-stimulated human leukocytes contains factors that induce human promyelocytic cell lines to differentiate along the monocytic pathway. In this report, we show that human promyelocytic cell lines are also induced to differentiate along this pathway by immune interferon (IFN gamma). Various preparations of IFN alpha tested did not induce this differentiation. In cultures containing IFN gamma, the cells are induced to coordinately express monocyte markers and functions such as monocyte-specific surface antigens, HLA-DR antigens, nonspecific esterase, receptors for the Fc fragment of IgG, and the ability to mediate antibody-dependent cell- mediated cytotoxicity. Our data indicate that differentiation induced by IFN gamma is not secondary to an arrest of growth of promyelocytic cell lines, but rather that a proportion of cells is induced along a programmed pathway of terminal differentiation similar to that of normal monocytes. CM contains IFN gamma, but its ability to induce differentiation is greater than expected on the basis of its content of IFN gamma. Treatments at 56 degrees C or at pH 2.0, which abolish IFN gamma activity, abrogate the differentiation ability of CM. The antiviral activity and the differentiation activity contained in the CM are coeluted from gel filtration and reverse-phase columns. Monoclonal antibodies anti-IFN gamma, which completely abrogate the differentiation ability of IFN gamma and the antiviral activity in the CM, completely suppress the induction of some monocyte markers by CM, but only reduce the expression of others. When IFN gamma is added to CM, promyelocytic cell lines are induced to differentiate to a much greater extent than that induced by either IFN gamma or IFN gamma- depleted CM alone. These results show that the differentiation activity of leukocyte CM is due to the synergistic effect of IFN gamma and other factors not yet identified.     

Reconstruction of the patterns of gene expression in the developing mouse heart reveals an architectural arrangement that facilitates the understanding of atrial malformations and arrhythmias

Firm knowledge about the formation of the atrial components and of the variations seen in congenital cardiac malformations and abnormal atrial rhythms is fundamental to our understanding of the normal structure of the definitive atrial chambers. The atrial region is relatively inaccessible and has continued to be the source of disagreement. Seeking to resolve these controversies, we made three-dimensional reconstructions of the myocardial components of the developing atrium, identifying domains on the basis of differential expression of myocardial markers, connexin40, and natriuretic precursor peptide A. These reconstructions, made from serial sections of mouse embryos, show that from the outset of atrial development, the systemic and pulmonary veins are directly connected to the atrium. Relative to the systemic junctions, however, the pulmonary venous junction appears later. Our experience shows that three-dimensional reconstructions have three advantages. First, they provide clear access to the combined morphological and molecular data, allowing clarification and verification of morphogenetic concepts for nonmorphological experts and setting the scene for further discussion. Second, they demonstrate that, from the outset, the myocardium surrounding the pulmonary veins is distinct from that clothing the systemic venoatrial junctions. Third, they reveal an anatomical and molecular continuity between the entrance of the systemic venous tributaries, the internodal atrial myocardium, and the atrioventricular region. All these regions are derived from primary myocardium, providing a molecular basis for the observed nonrandom distribution of focal right atrial tachycardias.     

Chronic blockade of bioelectric activity in neonatal rat neocortex in vitro:Physiological effects

We have examined what effect the loss of spontaneous bioelectric activity has on neural network formation in organotypic rat neocortical explants grown under serum-free culture conditions. Explants were taken from dorsal midline (presumptive visual) and lateral (presumptive auditory) occipital cortex and chronically exposed to tetrodotoxin which blocked all measurable bioelectric activity between change of medium. Extracellular recordings revealed complex, rhythmic spontaneous and evoked multiunit discharges in all explants examined (following tetrodotoxin washout in the experimental group). Control auditory explants had significantly more sites from which electric activity could be recorded compared with control visual explants. Auditory cultures showed no effect of the tetrodotoxin treatment, whereas visual explants showed significant increases over control values, equalling the auditory values. This increased level of spontaneous bioelectric activity was maintained for at least 10 days following transfer of the cultures to control growth medium. There was no significant difference between control visual and auditory explants regarding the number of sites from which evoked activity was seen. Nor did either cortex group show an effect of tetrodotoxin on the number of sites from which evoked activity was seen. The frequency with which spontaneous bioelectric discharges occurred per site increased with age in auditory vs visual cortex. These differences, however, were abolished in the tetrodotoxin-treated groups. It was concluded that neocortical explants which have experienced chronic suppression of spontaneous electric activity did not suffer deficits in neural network formation, though there is an effect on the incidence and frequency with which such activity is given.     

Cell number, tissue thickness and protein content as measures for development and variability in cultured neocortex explants

The development of neuronal number, explant thickness and amount of protein was studied in several series of rat neocortex expiants, cultured up to 21 days in vitro (DIV). In contrast to the dimensions of the explant, which rapidly stabilized, the amount of protein showed a prolonged increase with age in vitro. The number of neurons initially tended to decrease until a constant level was reached from 14 to 21 DIV. These findings are in good agreement with previously described cytoarchitectural characteristics. The present data also provided an opportunity to calculate the variance for various parameters within and between culture series obtained from different rats. Especially for the amount of protein, the variance between culture series appeared to be larger than within culture series. This difference was present already at the onset of culturing and persisted during development in vitro. Implications of these findings for experimental design are discussed.