Dual Atrioventricular Nodal Pathways Physiology: A Review of Relevant Anatomy,Electrophysiology, and Electrocardiographic Manifestations

More than half a century has passed since the concept of dual atrioventricular (AV) nodal pathways physiology was conceived. Dual AV nodal pathways have been shown to be responsible for many clinical arrhythmia syndromes, most notably AV nodal reentrant tachycardia. Although there has been a considerable amount of research on this topic, the subject of dual AV nodal pathways physiology remains heavily debated and discussed. Despite advances in understanding arrhythmia mechanisms and the widespread use of invasive electrophysiologic studies, there is still disagreement on the anatomy and physiology of the AV node that is the basis of discontinuous antegrade AV conduction. The purpose of this paper is to review the concept of dual AV nodal pathways physiology and its varied electrocardiographic manifestations.     

Life-long tailoring of diagnosis and management of patients with idiopathic ventricular fibrillation—future perspectives in research

The diagnosis and management of idiopathic ventricular fibrillation is challenging, as it requires extensive diagnostic testing and offers few curative options due to unknown underlying disease. The resulting population is a heterogeneous group of patients with a largely unknown natural history. Structural patient characterisation, follow-up and innovations in diagnostic testing can improve our understanding of the disease mechanisms of idiopathic ventricular fibrillation, detect underlying disease during follow-up and aid in therapeutic management. Recently, initiatives have been launched in the Netherlands to investigate the role of high-resolution non-invasive electrocardiographic imaging and genetic and familial screening in idiopathic ventricular fibrillation.     

Genetic susceptibility, evolution and the kuru epidemic

The acquired prion disease kuru was restricted to the Fore and neighbouring linguistic groups of the Papua New Guinea highlands and largely affected children and adult women. Oral history documents the onset of the epidemic in the early twentieth century, followed by a peak in the mid-twentieth century and subsequently a well-documented decline in frequency. In the context of these strong associations (gender, region and time), we have considered the genetic factors associated with susceptibility and resistance to kuru. Heterozygosity at codon 129 of the human prion protein gene (PRNP) is known to confer relative resistance to both sporadic and acquired prion diseases. In kuru, heterozygosity is associated with older patients and longer incubation times. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are predominantly PRNP codon 129 heterozygotes and this group show marked Hardy-Weinberg disequilibrium. The deviation from Hardy-Weinberg equilibrium is most marked in elderly women, but is also significant in a slightly younger cohort of men, consistent with their exposure to kuru as boys. Young Fore and the elderly from populations with no history of kuru show Hardy-Weinberg equilibrium. An increasing cline in 129V allele frequency centres on the kuru region, consistent with the effect of selection in elevating the frequency of resistant genotypes in the exposed population. The genetic data are thus strikingly correlated with exposure. Considering the strong coding sequence conservation of primate prion protein genes, the number of global coding polymorphisms in man is surprising. By intronic resequencing in a European population, we have shown that haplotype diversity at PRNP comprises two major and divergent clades associated with 129M and 129V. Kuru may have imposed the strongest episode of recent human balancing selection, which may not have been an isolated episode in human history.     

Idiopathic pulmonary fibrosis: a historical review.

Hamman and Rich are generally considered to have been the first to describe idiopathic pulmonary fibrosis (IPF) as a new clinical and pathological entity. However, several earlier reports in the German-language literature described autopsy findings consistent with IPF from a contemporary point of view. The author discusses these and later reports in a review of the history, diagnosis and treatment of the disease.     

May fever trigger ventricular fibrillation?

The clinical precipitants of ventricular fibrillation (VF) remain poorly understood. Clinical factors such as hypoxemia, acidosis or electrolyte imbalance, drug-related toxicity, autonomic nervous system disorders as well as viral myocarditis have been proposed to be associated with sudden cardiac death particularly in patients with structural heart disease. However, In the Brugada syndrome, concurrent febrile illness has been reported to unmask the electrocardiographic features of the Brugada syndrome and be associated with an increased propensity for VF. More recently, a febrile illnesses of infectious etiology was associated to polymorphic ventricular tachycardia or VF in patients with normal hearts and without known repolarization abnormality. In this review we detail this phenomenon and its putative mechanisms.     

ST segment elevation on electrocardiogram: the electrocardiographic pattern of Brugada syndrome

A 77-year-old white diabetic woman was brought to our emergency department (ED) after becoming lightheaded and hypotensive at home. Her routine tests including a chest radiograph were normal. Her electrocardiogram (ECG) showed significant ST segment elevation in leads V1 to V4. Serial cardiac enzymes and troponin were within normal limits. Her ECG met the criteria for type 1 Brugada syndrome. Brugada syndrome, which is more common in young Asian males, is an arrhythmogenic disease caused in part by mutations in the cardiac sodium channel gene SCN5A. To diagnose the Brugada syndrome, 1 ECG criterion and 1 clinical criterion should exist. Brugada syndrome can be associated with ventricular tachycardia or fibrillation; the only treatment proven to prevent sudden death is placement of an implantable cardioverter defibrillator, which is recommended in symptomatic patients or in those with ventricular tachycardia induced during electrophysiologic studies and a type 1 ECG pattern of Brugada syndrome. It is important to recognize the Brugada ECG pattern and to differentiate it from other etiologies of ST segment elevation on ECG.     

A case of isolated, corrected transposition of great arteries diagnosed with non-invasive techniques]

A case of a 34-year female patient with the isolated transposition of the great arterial trunks and mild atrioventricular (tricuspid) valve insufficiency is presented. The disease was diagnosed with non-invasive technique, particularly echocardiography. Cardiac disorders being usually concomitant with this syndrome (interventricular leak, pulmonary arterial wedge stenosis etc.) have been excluded by the aid of the contrast echographic technique and Doppler technique. The results of electrocardiographic records, which are usually helpful in the diagnosis of this abnormality have been completely useless in this case due to atypical ventricular depolarization vector pattern (QS complex in V1-V6 leads).     

Limiting sarcolemmal Na+ entry during resuscitation from ventricular fibrillation prevents excess mitochondrial Ca2+ accumulation and attenuates myocardial injury.

BACKGROUND: intracellular Na+ accumulation during ischemia and reperfusion leads to cytosolic Ca2+ overload through reverse-mode operation of the sarcolemmal Na+ -Ca2+ exchanger. Cytosolic Ca2+ accumulation promotes mitochondrial Ca2+ (Ca2+ m) overload, leading to mitochondrial injury. We investigated whether limiting sarcolemmal Na+ entry during resuscitation from ventricular fibrillation (VF) attenuates Ca2+ m overload and lessens myocardial dysfunction in a rat model of VF and closed-chest resuscitation. METHODS: hearts were harvested from 10 groups of 6 rats each representing baseline, 15 min of untreated VF, 15 min of VF with chest compression given for the last 5 min (VF/CC), and 60 min postresuscitation (PR). VF/CC and PR included four groups each randomized to receive before starting chest compression the new NHE-1 inhibitor AVE4454B (1.0 mg/kg), the Na+ channel blocker lidocaine (5.0 mg/kg), their combination, or vehicle control. The left ventricle was processed for intracellular Na+ and Ca2+ m measurements. RESULTS: limiting sarcolemmal Na+ entry attenuated cytosolic Na+ increase during VF/CC and the PR phase and prevented Ca2+ m overload yielding levels that corresponded to 77% and 71% of control hearts at VF/CC and PR, without differences among specific Na+ -limiting interventions. Limiting sarcolemmal Na+ entry attenuated reductions in left ventricular compliance during VF and prompted higher mean aortic pressure (110 +/- 7 vs. 95 +/- 11 mmHg, P < 0.001) and higher cardiac work index (159 +/- 34 vs. 126 +/- 29 g x m x min(-1) x kg(-1), P < 0.05) with lesser increases in circulating cardiac troponin I at 60 min PR. CONCLUSIONS: Na+ -limiting interventions prevented excess Ca2+ m accumulation induced by ischemia and reperfusion and ameliorated myocardial injury and dysfunction.     

Cross-sectional study of electrocardiographic pattern in healthy children resident at high altitude

Electrocardiographic studies have reported persistent right ventricle predominance in high altitude children as an adaptive response. No information was provided on ethnicity and environmental factors in those studies. We assessed the electrocardiographic characteristics in healthy high altitude children with mixed ancestry and relatively high mobility to lower altitudes. A cross-sectional study of 321 children aged 2 months through 19 years old and living at high altitude (Tintaya, Peru, 4,100 m) was conducted. Standard 12-lead electrocardiography was performed. Information was obtained on ethnicity, medical history, place and altitude of pregnancy and birth, mobility of children and their parents and grandparents to lower altitudes, and housing conditions. A medical examination, echocardiography, hemoglobin, oxygen saturation, and anthropometric measurements were performed. Means between sexes were compared through Mann-Whitney test for independent samples not normally distributed. Potentially influential variables on electrocardiographic values were controlled through a general linear model. Electrocardiographic parameters including QRS axis, RV1, RSV1, RV1SV5, RSV5, RSV6, and SV1RV5 did not show a right predominance pattern at any age. Values were within sea level norms. None of the genetic or environmental factors controlled showed a consistent influence on the electrocardiographic variables. Our study showed an electrocardiographic pattern similar to that of sea level in high altitude children with some degree of high-altitude ancestry, comparatively well-nourished and with relatively high mobility to low altitudes.     

Approach to the asymptomatic patients with Brugada syndrome

Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of coved-type ST segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD) as a result of polymorphic ventricular tachyarrhythmia or ventricular fibrillation (VF). Data from large patient studies and a meta-analysis of previous reports have shown that patients with a history of syncope or SCD and a spontaneous type 1 Brugada type ECG are at high risk for SCD. However, risk stratification of asymptomatic patients with Brugada type ECG is still a challenge. In particular, the use of electrophysiological study (EPS) for risk stratification remains controversial. Although some investigators have reported the possibility of use of EPS for distinguishing between high- and low-risk patients with Brugada type ECG, no precise predictor of risk for SCD in asymptomatic patients has yet been determined. The approach to treatment of these patients is thus still unclear. Large clinical prospective studies with uniform diagnostic criteria and protocols for EPS as well as extended follow-up periods of over ten years are required for prediction of SCD.     

Ventricular fibrillation: the current methods for analysing the degree of irregularity of the process

Ventricular fibrillation has traditionally been described as "chaotic" and in recent years there has been discussions that fibrillation may be an instance of deterministic chaos in the context of nonlinear dynamical systems theory. The current paper summarizes modern methods of mathematical analysis of the degree of electrical irregularities of the heart during VF. The traditional methods of Fourier analysis of electrocardiographic data as well as concepts of chaos theory--fractal dimension, entropy, reconstruction of attractors and some new methods such as spatial coherence have been considered. The results are discussed in context of mathematical models and hypothesis of mechanisms of VF.     

A radiographic study of porotic hyperostosis

Skull lesions known as porotic hyperostosis have been of interest to researchers since the mid-19th century. The etiology of porotic hyperostosis has long been a matter for speculation yet there has never been complete acceptance or substantiation of any one of the many theories proposed. Today the most widely accepted theory suggests that anemias of either acquired or genetic origin are responsible for porotic hyperostosis. The present study tests this hypothesis using criteria which were chosen after the examination of clinical radiographs of patients with various types of anemia. These criteria are: the presence of “hair-on-end” trabeculation, outer table thinning, texture changes, diploic thickening, orbital roof thickening, orbital rim changes, and the underdevelopment of frontal sinuses. A comparison of these criteria from the clinical X-rays with X-rays of skulls with porotic hyperostosis provides a more rigorous, repeatable, and standardized method upon which to base a diagnosis. This approach enables radiography to provide the necessary link between the clinical and anthropological with which to investigate the origin of porotic hyperostosis.     

Left septal fascicular block: myth or reality?

Anatomic studies have shown that the left bundle branch divides into three fascicles in most humans. Changes in the 12 lead ECG (electrocardiogram) due to conduction abnormalities of the left anterior fascicle and left posterior fascicle are now part of the standard repertoire of electrocardiographic interpretation. There are no standard criteria for detecting conduction defects involving the third left fascicle, the septal or median fascicle, and the very existence of such defects is still a matter of controversy. The purposes of this article are to review the available evidence on this subject, suggest electrocardiographic criteria for its recognition, and present examples which illustrate that left septal fascicular block does indeed exist as a specific entity. Left septal fascicular block is a polymorphic conduction defect which may explain some previously inadequately understood electrocardiographic abnormalities.     

Role of visceral adipose tissue in aging

Background

Visceral fat (VF) accretion is a hallmark of aging in humans. Epidemiologic studies have implicated abdominal obesity as a major risk factor for insulin resistance, type 2 diabetes, cardiovascular disease, metabolic syndrome and death.

Methods

Studies utilizing novel rodent models of visceral obesity and surgical strategies in humans have been undertaken to determine if subcutaneous (SC) abdominal or VF are causally linked to age-related diseases.

Results

Specific depletion or expansion of the VF depot using genetic or surgical tools in rodents has been shown to have direct effects on disease risk. In contrast, surgically removing large quantities of SC fat does not consistently improve metabolic parameters in humans or rodents, while benefits were observed with SC fat expansion in mice, suggesting that SC fat accrual is not an important contributor to metabolic decline. There is also compelling evidence in humans that abdominal obesity is a stronger risk factor for mortality risk than general obesity. Likewise, we have shown that surgical removal of VF improves mean and maximum lifespan in rats, providing the first causal evidence that VF depletion may be an important underlying cause of improved lifespan with caloric restriction.

General significance

This review provides both corollary and causal evidence for the importance of accounting for body fat distribution, and specifically VF, when assessing disease and mortality risk. Given the hazards of VF accumulation on health, treatment strategies aimed at selectively depleting VF should be considered as a viable tool to effectively reduce disease risk in humans.     

Mauriac syndrome still exists

Background/objectiveMauriac syndrome (MS) is a rare complication of type 1 diabetes mellitus (DM1). It is related to low insulin concentrations and is less common since longer-acting insulins became available. It is characterized by hepatomegaly, growth and puberty delay, and the presence of elevated transaminases and serum lipids. The aim of this study was to describe the patients from a pediatric diabetic population that fulfill the criteria of MS.Materials and methodsA retrospective analysis of the pediatric diabetic population with diagnostic criteria of MS currently followed at Hospital de Braga, was performed.ResultsFrom a population of 91 patients with DM1 18 years, 6 patients with the criteria for MS were identified: 5 girls, and 1 boy. The age at presentation was 13–17 years, with a minimum interval between DM1 diagnosis and MS criteria of 4 years. All the patients were prescribed intensive insulin therapy (median daily insulin dose: 0.88 U/kg). All had a previous history of poor glycemic control before the diagnosis of MS with glycated hemoglobin (HbA1c) between 8.8 and 12.9%. Increase of hepatic enzymes was present in all the patients; 4 of them had associated hepatomegaly. All the girls presented puberty delay and cushingoid features. None of the patients presented short stature and 5 of them presented mixed dyslipidemia.ConclusionsAlthough MS is an ancient entity described in DM1, it still exists, particularly in adolescent females. Being aware of MS is of extreme importance since most of the clinical features are reversible with better glycemic control.     

Exposure to sodium tungstate and Respiratory Syncytial Virus results in hematological/immunological disease in C57BL/6J mice

The etiology of childhood leukemia is not known. Strong evidence indicates that precursor B-cell Acute Lymphoblastic Leukemia (Pre-B ALL) is a genetic disease originating in utero. Environmental exposures in two concurrent, childhood leukemia clusters have been profiled and compared with geographically similar control communities. The unique exposures, shared in common by the leukemia clusters, have been modeled in C57BL/6 mice utilizing prenatal exposures. This previous investigation has suggested in utero exposure to sodium tungstate (Na2WO4) may result in hematological/immunological disease through genes associated with viral defense. The working hypothesis is (1) in addition to spontaneously and/or chemically generated genetic lesions forming pre-leukemic clones, in utero exposure to Na2WO4 increases genetic susceptibility to viral influence(s); (2) postnatal exposure to a virus possessing the 1FXXKXFXXA/V9 peptide motif will cause an unnatural immune response encouraging proliferation in the B-cell precursor compartment. This study reports the results of exposing C57BL/6J mice to Na2WO4 in utero via water (15 ppm, ad libetum) and inhalation (mean concentration PM5 3.33 mg/m3) and to Respiratory Syncytial Virus (RSV) within 2 weeks of weaning. Inoculation of C57BL/6J mice with RSV was associated with a neutrophil shift in 56% of 5-month old mice. When the RSV inoculation was combined with Na2WO4-exposure, significant splenomegaly resulted (p=0.0406, 0.0184, 0.0108 for control, Na2WO4-only and RSV-only, respectively) in addition to other hematological pathologies which were not significant. Exposure to Na2WO4 and RSV resulted in hematological/immunological disease, the nature of which is currently inconclusive. Further research is needed to characterize this potential leukemia mouse model.     

Geographical variation of mitochondrial DNA between populations of the white-clawed crayfish Austropotamobius pallipes

1. The white-clawed crayfish Austropotamobius pallipes has a widespread distribution in Europe, but since the last century its distribution has been severely affected by a combination of factors, particularly the disease crayfish plague, introduced by foreign crayfish species. At present A. pallipes is considered as vulnerable and endangered and measures are being taken in a number of countries to conserve it.
2. The application of genetics to conservation is of practical value particularly where restocking is being considered. This study assesses levels of genetic differentiation from an analysis of mitochondrial DNA (mtDNA) variation by restriction fragment length polymorphism of four populations sampled on a European scale. Six different composite haplotypes were detected among sixty-four crayfish representing the four populations. mtDNA nucleon diversity values within species ranged from 0.63% to 12.35%. A close genetic similarity was found between British and French populations of A. pallipes .
3. Results show that mtDNA can be as a suitable diagnostic marker for measuring genetic diversity between crayfish populations and that such information is of use in planning crayfish conservation strategies.     

Geographical variation of mitochondrial DNA between populations of the white-clawed crayfish Austropotamobius pallipes

1. The white-clawed crayfish Austropotamobius pallipes has a widespread distribution in Europe, but since the last century its distribution has been severely affected by a combination of factors, particularly the disease crayfish plague, introduced by foreign crayfish species. At present A. pallipes is considered as vulnerable and endangered and measures are being taken in a number of countries to conserve it.
2. The application of genetics to conservation is of practical value particularly where restocking is being considered. This study assesses levels of genetic differentiation from an analysis of mitochondrial DNA (mtDNA) variation by restriction fragment length polymorphism of four populations sampled on a European scale. Six different composite haplotypes were detected among sixty-four crayfish representing the four populations. mtDNA nucleon diversity values within species ranged from 0.63% to 12.35%. A close genetic similarity was found between British and French populations of A. pallipes .
3. Results show that mtDNA can be as a suitable diagnostic marker for measuring genetic diversity between crayfish populations and that such information is of use in planning crayfish conservation strategies.     

Molecular mechanisms,prevalence, and molecular methods for familial combined hyperlipidemia disease: A review

Familial combined hyperlipidemia (FCHL) is the most common genetic dyslipidemia disorder which is accompanied by increasing of triglyceride and cholesterol. This disorder is a complex genetic disease although it also has monogenic forms. The familial form has several criteria for diagnosis that can be distinguished of nonfamilial position. It has been shown that a variety of internal and external risk factors are involved in the pathogenesis of FCHL. Environmental factors and the genetic background also play an important role in the FCHL pathogenesis. Many mechanisms and pathways are involved in lipid metabolism (ie, dysfunctional adipose tissue, hepatic fat and very low-density lipoprotein overproduction, triglyceride-rich lipoproteins, and clearance of low-density lipoprotein particles) that could lead to FCHL. Individuals with a positive family history like those who have a positive family history of cardiovascular diseases are more predispositions for this disorder. To date several methods have been used to identify the genetic background of the FCHL. In the current review, we summarized the prevalence and the molecular mechanisms involved in the FCHL disease. Moreover, we highlighted the used molecular methods for determining the genes involved in the FCHL.