Cellular adaptation to cancer therapy along a resistance continuum.

Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance1. In addition to genetic mutations2, recent research has identified a role for non-genetic plasticity in transient drug tolerance3 and the acquisition of stable resistance4,5. However, the dynamics of cell-state transitions that occur in the adaptation to cancer therapies remain unknown and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell-state transitions accompanied by a progressive increase in cell fitness, which we denote as the 'resistance continuum'. This cellular adaptation involves a stepwise assembly of gene expression programmes and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that epithelial-to-mesenchymal transition or stemness programmes-often considered a proxy for phenotypic plasticity-enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify the acquisition of metabolic dependencies, exposing vulnerabilities that can potentially be exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell-state transitions.

Resident pharmacist participation in shared medical appointments in palliative care in São Paulo, Brazil: experience and contributions.

OBJECTIVE: To describe the resident pharmacist's participation in Shared Medical Appointments (SMA) in palliative care. METHODS: The resident pharmacist participated in face-to-face SMA with the attending physician, medical and gerontology students, and a nurse. KEY FINDINGS: The resident pharmacist supported interdisciplinary discussions and performed pharmaceutical interventions. He helped raise awareness about the effective, safe, and convenient use of medicines, helping improve the quality of life of patients and caregivers. CONCLUSIONS: Providing pharmaceutical care to patients in palliative care helped to improve the quality of clinical services offered to these patients, as well as adding value to resident pharmacists' interprofessional practice.

A Patient With Mental Disorder Wrongly Detained in a European Migrant Detention Centre.

The admission of undocumented migrants and refugees to detention centres (DC) has been systematically associated with several poor mental health outcomes. Much less is known about people with mental health disorders, non-migrants, who might be wrongfully committed to these facilities. This article draws on Dave's case, where a German citizen was detained in a migrant DC in Porto. The patient was later treated and diagnosed with schizophrenia. In light of another case report, we conceptualize the "Cornelia's phenomenon" by which a person with full citizenship rights but with a severe mental disorder is wrongly committed to a DC. We hypothesize that this worrisome phenomenon is underestimated, and we will discuss how pre-existent psychopathology might predispose vulnerable people to this situation. We will discuss the negative impact that detention might have on these patients, proposing solutions that might amend this worrisome phenomenon.

Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment.

Transcriptional heterogeneity among malignant cells of a tumor has been studied in individual cancer types and shown to be organized into cancer cell states; however, it remains unclear to what extent these states span tumor types, constituting general features of cancer. Here, we perform a pan-cancer single-cell RNA-sequencing analysis across 15 cancer types and identify a catalog of gene modules whose expression defines recurrent cancer cell states including 'stress', 'interferon response', 'epithelial-mesenchymal transition', 'metal response', 'basal' and 'ciliated'. Spatial transcriptomic analysis linked the interferon response in cancer cells to T cells and macrophages in the tumor microenvironment. Using mouse models, we further found that induction of the interferon response module varies by tumor location and is diminished upon elimination of lymphocytes. Our work provides a framework for studying how cancer cell states interact with the tumor microenvironment to form organized systems capable of immune evasion, drug resistance and metastasis.

Cancer cell states and emergent properties of the dynamic tumor system.

Phenotypic heterogeneity within malignant cells of a tumor is emerging as a key property of tumorigenesis. Recent work using single-cell transcriptomics has led to the identification of distinct cancer cell states across a range of cancer types, but their functional relevance and the advantage that they provide to the tumor as a system remain elusive. We present here a definition of cancer cell states in terms of coherently and differentially expressed gene modules and review the origins, dynamics, and impact of states on the tumor system as a whole. The spectrum of cell states taken on by a malignant population may depend on cellular lineage, epigenetic history, genetic mutations, or environmental cues, which has implications for the relative stability or plasticity of individual states. Finally, evidence has emerged that malignant cells in different states may cooperate or compete within a tumor niche, thereby providing an evolutionary advantage to the tumor through increased immune evasion, drug resistance, or invasiveness. Uncovering the mechanisms that govern the origin and dynamics of cancer cell states in tumorigenesis may shed light on how heterogeneity contributes to tumor fitness and highlight vulnerabilities that can be exploited for therapy.

Exploring tissue architecture using spatial transcriptomics.

Deciphering the principles and mechanisms by which gene activity orchestrates complex cellular arrangements in multicellular organisms has far-reaching implications for research in the life sciences. Recent technological advances in next-generation sequencing- and imaging-based approaches have established the power of spatial transcriptomics to measure expression levels of all or most genes systematically throughout tissue space, and have been adopted to generate biological insights in neuroscience, development and plant biology as well as to investigate a range of disease contexts, including cancer. Similar to datasets made possible by genomic sequencing and population health surveys, the large-scale atlases generated by this technology lend themselves to exploratory data analysis for hypothesis generation. Here we review spatial transcriptomic technologies and describe the repertoire of operations available for paths of analysis of the resulting data. Spatial transcriptomics can also be deployed for hypothesis testing using experimental designs that compare time points or conditions-including genetic or environmental perturbations. Finally, spatial transcriptomic data are naturally amenable to integration with other data modalities, providing an expandable framework for insight into tissue organization.

Association Between Intra-Hospital Uncontrolled Glycemia and Health Outcomes in Patients with Diabetes: A Systematic Review of Observational Studies.

BACKGROUND: Many people are still getting affected by uncontrolled glycemic events during hospital admission, which encompasses hypoglycemia, hyperglycemia, and high glycemic variability. INTRODUCTION: Primary studies have shown an association of glycemic dysregulation with increased length of hospital stay and mortality among overall patients, however, there is no systematic review of current evidence on the association between uncontrolled in-hospital glycemia in patients with diabetes and health outcomes. This study aimed to systematically review the current evidence on the association between uncontrolled in-hospital glycemia in patients with diabetes and health outcomes. METHODS: The association between glycemic dysregulation and health outcomes for inpatients with diabetes was systematically reviewed. PubMed, Embase, and LILACS databases were searched. Two independent reviewers were involved in each of the following steps: screening titles, abstracts, and fulltexts; assessing the methodological quality; and extracting data from included reviews. Descriptive analysis method was used. RESULTS: Seven cohort studies were included, and only two had a prospective design, consisting of 7,174 hospitalized patients with diabetes. In-hospital occurrence of hypoglycemia, hyperglycemia, and glycemic variability were assessed, and outcomes were mortality, infections, renal complications, and adverse events. Among the exposure and outcomes, an association was observed between severe hypoglycemia and mortality, hyperglycemia and infection, and hyperglycemia and adverse events. CONCLUSION: In-hospital uncontrolled glycemia in patients with diabetes is associated with poor health outcomes. More studies should be conducted for proper investigation because diabetes is a complex condition. Effects of glycemic dysregulation should be investigated on the basis of overall health of a patient instead from only organ-target perspective, which makes the investigation difficult.

Case Report: Catatonic Stupor in Behavioral Variant Frontotemporal Dementia.

Catatonia is a psychomotor syndrome common to several medical and neuropsychiatric disorders. Here, we report on the case of a 95-year-old woman who underwent a radical change in personality characterized by sexual disinhibition, and physical and verbal aggressiveness. Over several months, she developed verbal stereotypies, gait deterioration, and double incontinence. She eventually developed mutism and an active opposition to all attempts to be fed or cared for. Benzodiazepines, olanzapine and electroconvulsive therapy were of no benefit. Magnetic resonance imaging revealed asymmetric (more severe on the right) frontotemporal, parietal, and upper brainstem atrophy. She died from sepsis without recovering from stupor seven years after the onset of symptoms. We believe that the initial behavioral disinhibition was related to the frontotemporal injury, whereas catatonic stupor reflected the progression of the degenerative process to the parietal cortices. Our case adds to the small number of cases of catatonia as a symptom of degenerative dementia. It also supports the idea that damage to the parietal cortex gives rise to pathological avoidance of which catatonic stupor represents an extreme form.

Attachment Style and Insight in Schizophrenia: a Cross-Sectional Study.

Attachment theory provides a model for understanding impairments in social and interpersonal functioning. Schizophrenia is a neuropsychiatry disorder frequently associated with compromised social functioning and limited social support networks. However, the relationship between attachment style and psychopathology dimensions, including insight, isn't fully understood To determine whether there is a relationship between the attachment style and markers for severity of schizophrenia and insight. We conducted a cross-sectional study of 41 patients with schizophrenia and 34 patients with non-psychotic disorders used as a control group. Patients were assessed using semi-structured diagnostic interviews and self-reporting questionnaires, including Adult Attachment Scale-Revised. The schizophrenia group was also given the Positive and Negative Syndrome Scale and the Markova and Berrios Insight Scale. Insecure attachment was overrepresented in the schizophrenic group, and this difference was mainly accounted for lower levels of dependence, representing a moderate effect size (Cohen's d = 0.32). In the schizophrenia group, the closeness and the dependence subscale were negatively correlated with psychopathology severity. Using a multiple regression analysis, the insight was predicted by attachment anxiety, accounting for 20% of the total variance (R2 = 0.199, p <0.05). Our data confirm previous evidence that insecure attachment is associated with schizophrenia and suggest that the less comfortable the patient is with closeness and intimacy the greater the severity of symptoms. Furthermore, our findings indicate that higher separation anxiety might predict a better insight.

Bimodal Evolutionary Developmental miRNA Program in Animal Embryogenesis.

miRNAs play essential roles in the mechanics of gene regulation, however, on an organismal-scale, the processes in which they are deployed are not well understood. Here, we adopt an evolutionary developmental approach to study miRNA function by examining their expression throughout embryogenesis in both Caenorhabditis elegans and Drosophila melanogaster. We find that, in both species, miRNA transcriptomic shifts in a punctuated fashion during the mid-developmental transition, specifying two dominant modes of early and late expression profiles. Strikingly, late-expressed miRNAs are enriched for phylogenetic conservation and function by fine-tuning the expression of their targets, implicating a role in the canalization of cell types during differentiation. In contrast, early expressed miRNAs are inversely expressed with their targets suggesting strong target-inhibition. Taken together, our work exposes a bimodal role for miRNA function during animal development, involving late-expressed physiological roles and early expressed repressive roles.

Unveiling the Impact of the Genomic Architecture on the Evolution of Vertebrate microRNAs.

Eukaryotic genomes frequently exhibit interdependency between transcriptional units, as evidenced by regions of high gene density. It is well recognized that vertebrate microRNAs (miRNAs) are usually embedded in those regions. Recent work has shown that the genomic context is of utmost importance to determine miRNA expression in time and space, thus affecting their evolutionary fates over long and short terms. Consequently, understanding the inter- and intraspecific changes on miRNA genomic architecture may bring novel insights on the basic cellular processes regulated by miRNAs, as well as phenotypic evolution and disease-related mechanisms.

Host gene constraints and genomic context impact the expression and evolution of human microRNAs.

Increasing evidence has shown that recent miRNAs tend to emerge within coding genes. Here we conjecture that human miRNA evolution is tightly influenced by the genomic context, especially by host genes. Our findings show a preferential emergence of intragenic miRNAs within old genes. We found that miRNAs within old host genes are significantly more broadly expressed than those within young ones. Young miRNAs within old genes are more broadly expressed than their intergenic counterparts, suggesting that young miRNAs have an initial advantage by residing in old genes, and benefit from their hosts' expression control and from the exposure to diverse cellular contexts and target genes. Our results demonstrate that host genes may provide stronger expression constraints to intragenic miRNAs in the long run. We also report associated functional implications, highlighting the genomic context and host genes as driving factors for the expression and evolution of human miRNAs.

MicroRNA Expression Signature Is Altered in the Cardiac Remodeling Induced by High Fat Diets.

Recent studies have revealed the involvement of microRNAs (miRNAs) in the control of cardiac hypertrophy and myocardial function. In addition, several reports have demonstrated that high fat (HF) diet induces cardiac hypertrophy and remodeling. In the current study, we investigated the effect of diets containing different percentages of fat on the cardiac miRNA expression signature. To address this question, male C57Bl/6 mice were fed with a low fat (LF) diet or two HF diets, containing 45 kcal% fat (HF45%) and 60 kcal% fat (HF60%) for 10 and 20 weeks. HF60% diet promoted an increase on body weight, fasting glycemia, insulin, leptin, total cholesterol, triglycerides, and induced glucose intolerance. HF feeding promoted cardiac remodeling, as evidenced by increased cardiomyocyte transverse diameter and interstitial fibrosis. RNA sequencing analysis demonstrated that HF feeding induced distinct miRNA expression patterns in the heart. HF45% diet for 10 and 20 weeks changed the abundance of 64 and 26 miRNAs in the heart, respectively. On the other hand, HF60% diet for 10 and 20 weeks altered the abundance of 27 and 88 miRNAs in the heart, respectively. Bioinformatics analysis indicated that insulin signaling pathway was overrepresented in response to HF diet. An inverse correlation was observed between cardiac levels of GLUT4 and miRNA-29c. Similarly, we found an inverse correlation between expression of GSK3ß and the expression of miRNA-21a-3p, miRNA-29c-3p, miRNA-144-3p, and miRNA-195a-3p. In addition, miRNA-1 overexpression prevented cardiomyocyte hypertrophy. Taken together, our results revealed differentially expressed miRNA signatures in the heart in response to different HF diets. J. Cell. Physiol. 231: 1771-1783, 2016. © 2015 Wiley Periodicals, Inc.

HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms.

Supertypes are groups of human leukocyte antigen (HLA) alleles which bind overlapping sets of peptides due to sharing specific residues at the anchor positions-the B and F pockets-of the peptide-binding region (PBR). HLA alleles within the same supertype are expected to be functionally similar, while those from different supertypes are expected to be functionally distinct, presenting different sets of peptides. In this study, we applied the supertype classification to the HLA-A and HLA-B data of 55 worldwide populations in order to investigate the effect of natural selection on supertype rather than allelic variation at these loci. We compared the nucleotide diversity of the B and F pockets with that of the other PBR regions through a resampling procedure and compared the patterns of within-population heterozygosity (He) and between-population differentiation (G ST) observed when using the supertype definition to those estimated when using randomized groups of alleles. At HLA-A, low levels of variation are observed at B and F pockets and randomized He and G ST do not differ from the observed data. By contrast, HLA-B concentrates most of the differences between supertypes, the B pocket showing a particularly high level of variation. Moreover, at HLA-B, the reassignment of alleles into random groups does not reproduce the patterns of population differentiation observed with supertypes. We thus conclude that differently from HLA-A, for which supertype and allelic variation show similar patterns of nucleotide diversity within and between populations, HLA-B has likely evolved through specific adaptations of its B pocket to local pathogens.

Comprehensive evaluation of the effectiveness of gene expression signatures to predict complete response to neoadjuvant chemoradiotherapy and guide surgical intervention in rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) may lead to complete tumor regression in rectal cancer patients. Prediction of complete response to nCRT may allow a personalized management of rectal cancer and spare patients from unnecessary radical total mesorectal excision with or without sphincter preservation. To identify a gene expression signature capable of predicting complete pathological response (pCR) to nCRT, we performed a gene expression analysis in 25 pretreatment biopsies from patients who underwent 5FU-based nCRT using RNA-Seq. A supervised learning algorithm was used to identify expression signatures capable of predicting pCR, and the predictive value of these signatures was validated using independent samples. We also evaluated the utility of previously published signatures in predicting complete response in our cohort. We identified 27 differentially expressed genes between patients with pCR and patients with incomplete responses to nCRT. Predictive gene signatures using subsets of these 27 differentially expressed genes peaked at 81.8% accuracy. However, signatures with the highest sensitivity showed poor specificity, and vice-versa, when applied in an independent set of patients. Testing previously published signatures on our cohort also showed poor predictive value. Our results indicate that currently available predictive signatures are highly dependent on the sample set from which they are derived, and their accuracy is not superior to current imaging and clinical parameters used to assess response to nCRT and guide surgical intervention.

Estudos sobre a organização genômica, evolução e expressão de microRNAs / Studies on the genomic organization, evolution and expression of microRNAs

Os microRNAs (miRNAs) são pequenos RNAs não codificadores de proteínas presentes na maioria dos eucariotos. Esses RNAs regulam a expressão gênica em nível pós-transcricional através do silenciamento de mRNAs-alvo que possuem sítios complementares às suas sequências, atuando em praticamente todos os processos celulares. Embora a estrutura e função dos miRNAs estejam bem caracterizadas, aspectos relacionados à sua organização genômica, evolução e atuação em doenças são tópicos que apresentam enormes lacunas. Nesta tese, utilizamos abordagens computacionais para investigar estes temas em três trabalhos. No primeiro, processamos e integramos um vasto volume de dados publicamente disponíveis referentes aos miRNAs e genes codificadores de proteínas para cinco espécies de vertebrados. Com isso, construimos uma ferramenta web que permite a fácil inspeção da organização genômica dos miRNAs em regiões inter e intragênicas, o acesso a dados de expressão de miRNAs e de genes codificadores de proteínas (classificados em genes hospedeiros e não hospedeiros de miRNAs), além de outras informações pertinentes. Verificamos que a ferramenta tem sido amplamente utilizada pela comunidade científica e acreditamos que ela possa facilitar a geração de hipóteses associadas à regulação dos miRNAs, principalmente quando estão inseridos em genes hospedeiros. No segundo estudo, buscamos compreender como o contexto genômico e a origem evolutiva dos genes hospedeiros influenciam a expressão e evolução dos miRNAs humanos. Nossos achados mostraram que os miRNAs intragênicos surgem preferencialmente em genes antigos (origem anterior à divergência de vertebrados). Observamos que os miRNAs inseridos em genes antigos têm maior abrangência de expressão do que os inseridos em genes novos. Surpreendentemente, miRNAs jovens localizados em genes antigos são expressos em um maior número de tecidos do que os intergênicos de mesma idade, sugerindo uma vantagem adaptativa inicial que pode estar relacionada com o controle da expressão dos genes hospedeiros, e como consequência, expondo-os a contextos celulares e conjuntos de alvos diversos. Na evolução a longo prazo, vimos que genes antigos conferem maior restrição nos padrões de expressão (menor divergência de expressão) para miRNAs intragênicos, quando comparados aos intergênicos. Também mostramos possíveis associações funcionais relacionadas ao contexto genômico, tais como o enriquecimento da expressão de miRNAs intergênicos em testículo e dos intragênicos em tecidos neurais. Propomos que o contexto genômico e a idade dos genes hospedeiros são fatores-chave para a evolução e expressão dos miRNAs. Por fim, buscamos estabelecer associações entre a expressão diferencial de miRNAs e a quimioresistência em câncer colorretal utilizando linhagens celulares sensíveis e resistentes às drogas 5-Fluoruracil e Oxaliplatina. Dentre os miRNAs identificados, o miR-342 apresentou níveis elevados de expressão nas linhagens sensíveis à Oxaliplatina. Com base na análise dos alvos preditos, detectamos uma significativa associação de miR-342 com a apoptose. A superexpressão de miR-342 na linhagem resistente SW620 evidenciou alterações na expressão de genes da via apoptótica, notavelmente a diminuição da expressão do fator de crescimento PDGFB, um alvo predito possivelmente sujeito à regulação direta pelo miR-342

MicroRNAs (miRNAs) are short non-coding RNAs found in most eukaryotic species. These RNAs regulate gene expression at post-transcriptional level by silencing target mRNAs through base-pairing of complementary sequences, thus acting on virtually all cellular processes. Although the structure and function of miRNAs are well understood, several aspects related to their genomic organization, evolution and involvement with diseases are largely underexplored. In this thesis, we employed computational methods to investigate such issues in three different studies. In the first one, we have processed and integrated a large amount of public data related to miRNAs and coding genes for five vertebrate species. Then, we developed a webtool to allow the analysis of the miRNA genomic context in inter and intragenic regions, the access of miRNA and gene expression data (classified as host and non-host genes), as well as other relevant information. We noticed that the webtool has been largely used by the scientific community, and we believe that it can facilitate hypothesis generation related to miRNA regulation, especially when they are within host genes. In the following study, we sought to understand how the genomic context and the evolutionary origin of host genes can affect the expression and evolution of human miRNAs. Our findings showed that intragenic miRNAs are preferentially embedded within old host genes (originated before the split of vertebrates). We observed that miRNAs within old genes are more broadly expressed than those within young genes. Surprisingly, young miRNAs within old genes were expressed in more tissues than their intergenic counterparts, suggesting an initial adaptive advantage which might be related to their hosts expression control, and as a consequence, exposing them to a more diverse cellular contexts and target genes. In the long run, we found that old host genes lead to expression constraints (lower expression divergence) between species for intragenic miRNAs, in respect to intergenic ones. We also showed possible functional associations related to miRNA genomic context, such as the enrichment of young intergenic miRNAs in testis, while young intragenic miRNAs were enriched in neural tissues. Thus, we propose that the genomic context and the age of the host genes are key factors in shaping the expression and evolution of miRNAs. Finally, we sought to establish associations between differential expression of miRNAs and chemoresistance in colorectal cancer using resistant and sensitive cell lines to 5-Fluoruracil and Oxaliplatin. Among differentially expressed miRNAs, miR-342 was highly expressed in sensitive cell lines to Oxaliplatin. Based on target prediction analysis, miR-342 is likely associated with apoptosis. The induced overexpression of miR-342 in SW620, a cell line resistant to Oxaliplatin, changed the expression levels of genes linked to the apoptosis pathway, notably the downregulation of PDGFB growth factor, which is a predicted target possibly subjected to direct regulation by miR-342

miRIAD-integrating microRNA inter- and intragenic data.

MicroRNAs (miRNAs) are a class of small (∼22 nucleotides) non-coding RNAs that post-transcriptionally regulate gene expression by interacting with target mRNAs. A majority of miRNAs is located within intronic or exonic regions of protein-coding genes (host genes), and increasing evidence suggests a functional relationship between these miRNAs and their host genes. Here, we introduce miRIAD, a web-service to facilitate the analysis of genomic and structural features of intragenic miRNAs and their host genes for five species (human, rhesus monkey, mouse, chicken and opossum). miRIAD contains the genomic classification of all miRNAs (inter- and intragenic), as well as classification of all protein-coding genes into host or non-host genes (depending on whether they contain an intragenic miRNA or not). We collected and processed public data from several sources to provide a clear visualization of relevant knowledge related to intragenic miRNAs, such as host gene function, genomic context, names of and references to intragenic miRNAs, miRNA binding sites, clusters of intragenic miRNAs, miRNA and host gene expression across different tissues and expression correlation for intragenic miRNAs and their host genes. Protein-protein interaction data are also presented for functional network analysis of host genes. In summary, miRIAD was designed to help the research community to explore, in a user-friendly environment, intragenic miRNAs, their host genes and functional annotations with minimal effort, facilitating hypothesis generation and in-silico validations. Database URL: http://www.miriad-database.org.

Aspectos comparativos da localização, distribuição e irrigação do nó atrioventricular em suínos (Sus domesticus) da raça Landrace / Comparatives aspects of localization, distribution and irrigation of the atrioventricular node in pigs (Sus domesticus) of the Landrace race

A análise morfológica buscou verificar a localização do nó e do fascículo atrioventriculares, bem como sua distribuição sob o endocárdio dos ventrículos e descrever as artérias responsáveis pela nutrição do nó, comparando tais aspectos com características já descritas em seres humanos. Foram coletados 30 corações de suínos Landrace, sendo fêmeas com idade entre 2,5 a 3 anos. Inicialmente, 10 corações foram dissecados a fresco, e outros 20 corações foram injetados com solução de neoprene látex, posteriormente fixados em formaldeído a 10% por 72 horas, para então serem dissecados. Foi observado que o nó atrioventricular localiza-se na região caudoventral do septo interatrial, próximo à abertura do seio coronário. Também foram observadas quatro tipos de irrigações, sendo que a principal irrigação encontrada nos suínos trata-se do primeiro ramo septal caudal, proveniente da artéria coronária direita. O fascículo atrioventricular atravessou o esqueleto fibroso em direção ao septo interventricular e se dividiu em dois ramos. O ramo direito desceu em direção ao ápice do coração sob o endocárdio, se distribuindo na parede lateral do ventrículo direito e o ramo esquerdo permaneceu único ou se dividiu em dois e três ramos, que se distribuíram na parede do ventrículo esquerdo. A localização e irrigação do nó atrioventricular, assim como a divisão e a distribuição do fascículo atrioventricular são semelhantes à anatomia humana, podendo ser viável a utilização de suínos como modelo experimental em estudos comparativos que investiguem esse sistema.

Morphological analysis aimed to verify the location of the node and the atrioventricular fasciculus, and its distribution in the endocardium of the ventricles and describe the arteries responsible for nourishing the node, comparing these aspects with features in humans. Were collected 30 Landrace pig hearts, females, 2.5 to 3 years. Initially, 10 hearts were fresh dissected, and in 20 others hearts were injected with neoprene latex solution, later fixed in 10% formaldehyde for 72 hours, then were dissected. It was observed that the atrioventricular node was located in the caudoventral region of the atrial septum, near the opening of the coronary sinus. It was also observed four types of irrigation, and the main irrigation found in pigs was the first septal branch caudal coming from the right coronary artery. The atrioventricular fascicle crossed the fibrous skeleton into the interventricular septum and split into two branches. The right branch came down towards the apex of the heart under the endocardium, up by distributing itself in the lateral wall of the right ventricle, and the left branch remained single or divided in two and three branches, which are distributed in the wall of the left ventricle. Location and irrigation of the atrioventricular node, as well as the division and distribution of fascicle, are similar to Human Anatomy, being viable the use of pigs as an experimental model in comparative studies to investigate this system.