Neuronal Stability, Volumetric Changes, and Decrease in GFAP Expression of Marmoset (Callithrix jacchus) Subcortical Visual Nuclei During Aging.

The physiological aging process is well known for functional decline in visual abilities. Among the components of the visual system, the dorsal lateral geniculate nucleus (DLG) and superior colliculus (SC) provide a good model for aging investigations, as these structures constitute the main visual pathways for retinal inputs reaching the visual cortex. However, there are limited data available on quantitative morphological and neurochemical aspects in DLG and SC across lifespan. Here, we used optical density to determine immunoexpression of glial fibrillary acidic protein (GFAP) and design-based stereological probes to estimate the neuronal number, total volume, and layer volume of the DLG and SC in marmosets (Callithrix jacchus), ranging from 36 to 143 months of age. Our results revealed an age-related increase in total volume and layer volume of the DLG, with an overall stability in SC volume. Furthermore, a stable neuronal number was demonstrated in DLG and superficial layers of SC (SCv). A decrease in GFAP immunoexpression was observed in both visual centers. The results indicate region-specific variability in volumetric parameter, possibly attributed to structural plastic events in response to inflammation and compensatory mechanisms at the cellular and subcellular level. Additionally, the DLG and SCv seem to be less vulnerable to aging effects in terms of neuronal number. The neuropeptidergic data suggest that reduced GFAP expression may reflect morphological atrophy in the astroglial cells. This study contributes to updating the current understanding of aging effects in the visual system and stablishes a crucial foundation for future research on visual perception throughout the aging process.

Neuropathological and sociodemographic factors associated with the cortical amyloid load in aging and Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia and is characterized by a progressive decline in cognitive abilities. A pathological hallmark of AD is a region-specific accumulation of the amyloid-beta protein (Aß). Here, we explored the association between regional Aß deposition, sociodemographic, and local biochemical factors. We quantified the Aß burden in postmortem cortical samples from parietal (PCx) and temporal (TCx) regions of 27 cognitively unimpaired (CU) and 15 AD donors, aged 78-100 + years. Histological images of Aß immunohistochemistry and local concentrations of pathological and inflammatory proteins were obtained at the "Aging, Dementia and TBI Study" open database. We used the area fraction fractionator stereological methodology to quantify the Aß burden in the gray and white matter within each cortical region. We found higher Aß burdens in the TCx of AD octogenarians compared to CU ones. We also found higher Aß loads in the PCx of AD nonagenarians than in AD octogenarians. Moreover, AD women exhibited increased Aß deposition compared to CU women. Interestingly, we observed a negative correlation between education years and Aß burden in the white matter of both cortices in CU samples. In AD brains, the Aß40, Aß42, and pTau181 isoforms of Aß and Tau proteins were positively correlated with the Aß burden. Additionally, in the TCx of AD donors, the proinflammatory cytokine TNFα showed a positive correlation with the Aß load. These novel findings contribute to understanding the interplay between sociodemographic characteristics, local inflammatory signaling, and the development of AD-related pathology in the cerebral cortex.

Layer-Specific Changes in the Prefrontal Glia/Neuron Ratio Characterizes Patches of Gene Expression Disorganization in Children with Autism.

Autism spectrum disorder (ASD) is manifested by abnormal cell numbers and patches of gene expression disruption in higher-order brain regions. Here, we investigated whether layer-specific changes in glia/neuron ratios (GNR) characterize patches in the dorsolateral prefrontal cortex (DL-PFC) of children with ASD. We analyzed high-resolution digital images of postmortem human brains from 11 ASD and 11 non-ASD children obtained from the Autism Study of the Allen Human Brain Atlas. We found the GNR is overall reduced in the ASD DL-PFC. Moreover, layers II-III belonging to patches presented a lower GNR in comparison with layers V-VI. We here provide a new insight into how brain cells are arranged within patches that contributes to elucidate how neurodevelopmental programs are altered in ASD.

Age, Education Years, and Biochemical Factors Are Associated with Selective Neuronal Changes in the Elderly Hippocampus.

Brain aging involves regional alterations of specific cellular subpopulations in the human hippocampus: a network hub for memory consolidation. The present study investigates whether age, sex, education years, and the concentration of neuropathological and inflammatory proteins influence neuronal-type marker expression in the elderly hippocampus. We analyzed the digital images (1 µm/pixel) of postmortem hippocampal sections from 19 non-demented individuals (from 78 to 99 years). This material was obtained from the "Aging Dementia and TBI Study" open database. Brain samples were processed through in situ hybridization (ISH) for the immunodetection of VGLUT1 (glutamatergic transporter) and GAT1 (GABAergic transporter) and mRNAs and Luminex protein quantifications. After image acquisition, we delineated the dentate gyrus, CA 3/2, and CA1 hippocampal subdivisions. Then, we estimated the area fraction in which the ISH markers were expressed. Increased VGLUT1 was observed in multiple hippocampal subfields at late ages. This glutamatergic marker is positively correlated with beta-amyloid and tau proteins and negatively correlated with interleukin-7 levels. Additionally, education years are positively correlated with GAT1 in the hippocampus of elderly women. This GABAergic marker expression is associated with interferon-gamma and brain-derived neurotrophic factor levels. These associations can help to explain how hippocampal sub-regions and neurotransmitter systems undergo distinct physiological changes during normal aging.

Prenatal exposure to fluoxetine modulates emotionality and aversive memory in male and female rat offspring.

During pregnancy, women are prone to depression, for which selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are usually the first-line treatment. However, fluoxetine can cross the placental barrier and affect fetuses, causing changes in serotonin levels early in life. Long-term effects in the brain circuits that control cognitive and emotional behavior are related to early fluoxetine exposure during development. In this study, we aimed to investigate whether fluoxetine exposure (10 mg/kg/day) from the 13th gestational day (GD13) to GD21 may lead to behavioral emotional-cognitive changes in male and female rat offspring approximately 90 days postnatally (~PN90). We have analyzed the performance of individuals in the open field and in the plus-maze discriminative avoidance task, which assesses anxiety and learning/memory processing behaviors. We have found that prenatal (GD13-GD21) exposure to fluoxetine strengthened aversive memory and induced higher anxiety levels in males, and quick extinction of aversive memory in females. Taken together, these results suggest that early exposure to fluoxetine impairs the basal state of anxiety and the cognitive functions of rats during adulthood, which may be in a sex-specific manner because males appear more susceptible than females.

All-Polymeric Electrode Based on PEDOT:PSS for In Vivo Neural Recording.

One of the significant challenges today in the brain-machine interfaces that use invasive methods is the stability of the chronic record. In recent years, polymer-based electrodes have gained notoriety for achieving mechanical strength values close to that of brain tissue, promoting a lower immune response to the implant. In this work, we fabricated fully polymeric electrodes based on PEDOT:PSS for neural recording in Wistar rats. We characterized the electrical properties and both in vitro and in vivo functionality of the electrodes. Additionally, we employed histological processing and microscopical visualization to evaluate the tecidual immune response at 7, 14, and 21 days post-implant. Electrodes with 400-micrometer channels showed a 12 dB signal-to-noise ratio. Local field potentials were characterized under two conditions: anesthetized and free-moving. There was a proliferation of microglia at the tissue-electrode interface in the early days, though there was a decrease after 14 days. Astrocytes also migrated to the interface, but there was not continuous recruitment of these cells in the tissue; there was inflammatory stability by day 21. The signal was not affected by this inflammatory action, demonstrating that fully polymeric electrodes can be an alternative means to prolong the valuable time of neural recordings.

Effects of prenatal exposure to fluoxetine on circadian rhythmicity in the locomotor activity and neuropeptide Y and 5-HT expression in male and female adult Wistar rats.

Serotonin (5-HT) reuptake inhibitors, such as fluoxetine, are the most prescribed antidepressant for maternal depression. In this sense, it exposes mothers and the brains of infants to increased modulatory and trophic effects of serotonergic neurotransmission. 5-HT promotes essential brain changes throughout its development, which include neuron migration, differentiation and organisation of neural circuitries related to emotional, cognitive and circadian behavior. Early exposure to the SSRIs induces long-term effects on behavioral and neural serotonergic signalisation. We have aimed to evaluate the circadian rhythm of locomotor activity and the neurochemical content, neuropeptide Y (NPY) and 5-HT in three brain areas: intergeniculate leaflet (IGL), suprachiasmatic nuclei (SCN) and raphe nuclei (RN), at two zeitgebers (ZT6 and ZT18), in male and female rat's offspring early exposed (developmental period GD13-GD21) to fluoxetine (20 mg/kg). First, we have conducted daily records of the locomotor activity rhythm using activity sensors coupled to individual cages over 4 weeks. We have lastly evaluated the immunoreactivity of NPY in both SCN and IGL, as well the 5-HT expression in the dorsal and medial RN. In summary, our results showed that (1) prenatal fluoxetine affects phase entrainment of the rest/activity rhythm at ZT6 and ZT18, more in male than female specimens, and (2) modulates the NPY and 5-HT expression. Here, we show male rats are more susceptible to phase entrainment and the NPY and 5-HT misexpression compared to female ones. The sex differences induced by early exposure to fluoxetine in both the circadian rhythm of locomotor activity and the neurochemical expression into SCN, IGL and midbrain raphe are an important highlight in the present work. Thus, our results may help to improve the knowledge on neurobiological mechanisms of circadian rhythms and are relevant to understanding the "broken brains" and behavioral abnormalities of offspring early exposed to antidepressants.

Association between mucosal surface pattern under near focus technology and Helicobacter pylori infection.

BACKGROUND: Many studies evaluated magnification endoscopy (ME) to correlate changes on the gastric mucosal surface with Helicobacter pylori (H. pylori) infection. However, few studies validated these concepts with high-definition endoscopy without ME. AIM: To access the association between mucosal surface pattern under near focus technology and H. pylori infection status in a western population. METHODS: Cross-sectional study including all patients referred to routine upper endoscopy. Endoscopic exams were performed using standard high definition (S-HD) followed by near focus (NF-HD) examination. Presence of erythema, erosion, atrophy, and nodularity were recorded during S-HD, and surface mucosal pattern was classified using NF-HD in the gastric body. Biopsies were taken for rapid urease test and histology. RESULTS: One hundred and eighty-seven patients were analyzed from August to November 2019. Of those, 47 (25.1%) were H. pylori+, and 42 (22.5%) had a previous H. pylori treatment. In the examination with S-HD, erythema had the best sensitivity for H. pylori detection (80.9%). Exudate (99.3%), nodularity (97.1%), and atrophy (95.7%) demonstrated better specificity values, but with low sensitivity (6.4%-19.1%). On the other hand, the absence of erythema was strongly associated with H. pylori- (negative predictive value = 92%). With NF-HD, 56.2% of patients presented type 1 pattern (regular arrangement of collecting venules, RAC), and only 5.7% of RAC+ patients were H. pylori+. The loss of RAC presented 87.2% sensitivity for H. pylori detection, 70.7% specificity, 50% positive predictive value, and 94.3% negative predictive value, indicating that loss of RAC was suboptimal to confirm H. pylori infection, but when RAC was seen, H. pylori infection was unlikely. CONCLUSION: The presence of RAC at the NF-HD exam and the absence of erythema at S-HD were highly predictive of H. pylori negative status. On the other hand, the loss of RAC had a suboptimal correlation with the presence of H. pylori.

Aging Alters Daily and Regional Calretinin Neuronal Expression in the Rat Non-image Forming Visual Thalamus.

Aging affects the overall physiology, including the image-forming and non-image forming visual systems. Among the components of the latter, the thalamic retinorecipient inter-geniculate leaflet (IGL) and ventral lateral geniculate (vLGN) nucleus conveys light information to subcortical regions, adjusting visuomotor, and circadian functions. It is noteworthy that several visual related cells, such as neuronal subpopulations in the IGL and vLGN are neurochemically characterized by the presence of calcium binding proteins. Calretinin (CR), a representative of such proteins, denotes region-specificity in a temporal manner by variable day-night expression. In parallel, age-related brain dysfunction and neurodegeneration are associated with abnormal intracellular concentrations of calcium. Here, we investigated whether daily changes in the number of CR neurons are a feature of the aged IGL and vLGN in rats. To this end, we perfused rats, ranging from 3 to 24 months of age, within distinct phases of the day, namely zeitgeber times (ZTs). Then, we evaluated CR immunolabeling through design-based stereological cell estimation. We observed distinct daily rhythms of CR expression in the IGL and in both the retinorecipient (vLGNe) and non-retinorecipient (vLGNi) portions of the vLGN. In the ZT 6, the middle of the light phase, the CR cells are reduced with aging in the IGL and vLGNe. In the ZT 12, the transition between light to dark, an age-related CR loss was found in all nuclei. While CR expression predominates in specific spatial domains of vLGN, age-related changes appear not to be restricted at particular portions. No alterations were found in the dark/light transition or in the middle of the dark phase, ZTs 0, and 18, respectively. These results are relevant in the understanding of how aging shifts the phenotype of visual related cells at topographically organized channels of visuomotor and circadian processing.

Pattern of tyrosine hydroxylase expression during aging of mesolimbic pathway of the rat.

Senescence is a physiological and progressive event that leads to the impairment of normal functions of the organism. The nervous system is one of the most affected systems during aging, presenting both structural and functional alterations associated with a decline in normal brain functions. In the present study we aimed to evaluate the impact of senescence on the mesolimbic pathway (nucleus accumbens - NAc and ventral tegmental area - VTA) of the rat, through immunohistochemistry for tyrosine hydroxylase (TH) enzyme, in young (3 months old), middle-aged (10 months old) and aged animals (18 months old). There was a significant decrease in the TH-immunoreactivity across NAc in aged animals as compared to the young and middle-aged ones, as revealed by optical densitometry. Medium and caudal regions of the VTA in the young animals possessed a higher number of TH-immunoreactive neurons as compared to the more aged groups. Comparisons among VTA regions in young animals revealed a difference in the number of cell bodies when the medium region was compared to the rostral and caudal regions whilst in both the middle-aged and aged groups comparisons between rostral vs caudal and medium vs caudal regions were significant. Our results show that aging impacts the mesolimbic pathway across its rostrocaudal axis, with a decrease of TH-reactivity in NAc and loss of neurons in VTA. These events may be involved with behavioral alterations observed throughout aging.

Region-specific glial hyperplasia and neuronal stability of rat lateral geniculate nucleus during aging.

The normal aging process is accompanied by functional declines in image-forming and non-image forming visual systems. Among the components of these systems, the thalamic lateral geniculate nucleus (LGN) offers a good model for aging studies since its three anatomical subdivisions, namely dorsal lateral geniculate nucleus (dLGN), intergeniculate leaflet (IGL) and ventral lateral geniculate nucleus (vLGN), receives light information from retina and projects to different brain areas involved in visual-related functions. Nevertheless, there is very little data available about quantitative morphological aspects in LGN across lifespan. In this study, we used design-based stereology to estimate the number of neurons, glial cells, the glia/neuron ratio and the volume of the LGN of Wistar rats from 3, 13 or 23months of age. We examined each LGN subdivision processed by immunohistochemistry for NeuN and Nissl counterstain. We observed no significant age-related neuronal loss in any nuclei and a 21% and 33% significant increase in dLGN and IGL glial cells of 23month-old rats. We also observed the glia/neuron relation increases in dLGN of 13month-old rats and in dLGN, IGL and vLGN internal portion of 23month-old ones. Moreover, we report an age-related increase in IGL volume. These results show region-specific glial hyperplasia during aging within LGN nuclei, perhaps due to compensatory responses to inflammation. In addition, we observed the glia/neuron ratio as a more sensitive parameter to quantify age-related alterations. Hence, we provide an updated and expanded quantitative characterization of these visual-related thalamic nuclei and its variability across lifespan.

Retinal, NPY- and 5ht- inputs to the aged suprachiasmatic nucleus in common marmosets (Callithrix jacchus).

The circadian timing system (CTS) anticipates optimal physiological patterns in response to environmental fluctuations, such as light-dark cycle. Since age-related disruption of circadian synchronization is linked to several pathological conditions, we characterized alterations of neurochemical constituents and retinal projections to the major pacemaker of CTS, the suprachiasmatic nucleus (SCN), in adult and aged marmosets. We used intraocular injections of neural tracer Cholera toxin b (CTb) to report age-related reductions in CTb, neuropeptide Y and serotonin immunoreactivities. Considering these projections arise in SCN from nuclei that relay environmental information to entrain the circadian clock, we provide important anatomical correlates to age-associated physiological deficits.

Nuclear organization of the substantia nigra, ventral tegmental area and retrorubral field of the common marmoset (Callithrix jacchus): A cytoarchitectonic and TH-immunohistochemistry study.

It is widely known that the catecholamine group is formed by dopamine, noradrenaline and adrenaline. Its synthesis is regulated by the enzyme called tyrosine hydroxylase. 3-hydroxytyramine/dopamine (DA) is a precursor of noradrenaline and adrenaline synthesis and acts as a neurotransmitter in the central nervous system. The three main nuclei, being the retrorubral field (A8 group), the substantia nigra pars compacta (A9 group) and the ventral tegmental area (A10 group), are arranged in the die-mesencephalic portion and are involved in three complex circuitries - the mesostriatal, mesolimbic and mesocortical pathways. These pathways are involved in behavioral manifestations, motricity, learning, reward and also in pathological conditions such as Parkinson's disease and schizophrenia. The aim of this study was to perform a morphological analysis of the A8, A9 and A10 groups in the common marmoset (Callithrix jacchus - a neotropical primate), whose morphological and functional characteristics support its suitability for use in biomedical research. Coronal sections of the marmoset brain were submitted to Nissl staining and TH-immunohistochemistry. The morphology of the neurons made it possible to subdivide the A10 group into seven distinct regions: interfascicular nucleus, raphe rostral linear nucleus and raphe caudal linear nucleus in the middle line; paranigral and parainterfascicular nucleus in the middle zone; the rostral portion of the ventral tegmental area nucleus and parabrachial pigmented nucleus located in the dorsolateral portion of the mesencephalic tegmentum. The A9 group was divided into four regions: substantia nigra compacta dorsal and ventral tiers; substantia nigra compacta lateral and medial clusters. No subdivisions were made for the A8 group. These results reveal that A8, A9 and A10 are phylogenetically stable across species. As such, further studies concerning such divisions are necessary in order to evaluate the occurrence of subdivisions that express DA in other primate species, with the aim of characterizing its functional relevance.

Age-related changes in neurochemical components and retinal projections of rat intergeniculate leaflet.

Aging leads to several anatomical and functional deficits in circadian timing system. In previous works, we observed morphological alterations with age in hypothalamic suprachiasmatic nuclei, one central component of this system. However, there are few data regarding aging effects on other central components of this system, such as thalamic intergeniculate leaflet (IGL). In this context, we studied possible age-related alterations in neurochemical components and retinal projections of rat IGL. For this goal, young (3 months), adult (13 months), and aged (23 months) Wistar rats were submitted to an intraocular injection of neural tracer, cholera toxin subunit b (CTb), 5 days before a tissue fixation process by paraformaldehyde perfusion. Optical density measurements and cell count were performed at digital pictures of brain tissue slices processed by immunostaining for glutamic acid decarboxylase (GAD), enkephalin (ENK), neuropeptide Y (NPY) and CTb, characteristic markers of IGL and its retinal terminals. We found a significant age-related loss in NPY immunoreactive neurons, but not in immunoreactivity to GAD and ENK. We also found a decline of retinal projections to IGL with age. We conclude aging impairs both a photic environmental clue afferent to IGL and a neurochemical expression which has an important modulatory circadian function, providing strong anatomical correlates to functional deficits of the aged biological clock.

Changes in the suprachiasmatic nucleus during aging: implications for biological rhythms

Animals have neural structures that allow them to anticipate environmental changes and then regulate physiological and behavioral functions in response to these alterations. The suprachiasmatic nucleus of the hypothalamus (SCN) is the main circadian pacemaker in many mammalian species. This structure synchronizes the biological rhythm based on photic information that is transmitted to the SCN through the retinohypothalamic tract. The aging process changes the structural complexity of the nervous system, from individual nerve cells to global changes, including the atrophy of total gray matter. Aged animals show internal time disruptions caused by morphological and neurochemical changes in SCN components. The effects of aging on circadian rhythm range from effects on simple physiological functions to effects on complex cognitive performance, including many psychiatric disorders that influence the well-being of the elderly. In this review, we summarize the effects of aging on morphological, neurochemical, and circadian rhythmic functions coordinated by the main circadian pacemaker, the SCN...

A report of a galactan from marine alga Gelidium crinale with in vivo anti-inflammatory and antinociceptive effects.

The sulfated galactan of the red marine alga Gelidium crinale (SG-Gc) was purified by ion exchange chromatography and tested by intravenous (i.v.) route in rodent experimental models of inflammation and nociception. The anti-inflammatory activity of SG-Gc (0.01, 0.1 and 1 mg/kg) was evaluated in the model of rat paw edema induced by different inflammatory stimuli, while SG-Gc (0.1, 1 and 10 mg/kg) antinociceptive effect was assessed in models of nociception/hyperalgesia elicited by chemical (formalin test), thermal (hot plate), and mechanical (von Frey) stimuli in mice. In addition, the toxicity was evaluated after rat treatment with SG-Gc (1 mg/kg; i.v.) during 10 days, followed by analysis of the wet weight of animal's body/organs and hematological/biochemical parameters. Sulfated galactan of G. crinale inhibited the time course of dextran-induced paw edema, at all doses, showing maximal effect at 1 mg/kg (42%) and that induced by carrageenan at 0.01 (18%) and 1 mg/kg (20%), but was ineffective on the edema elicited by zymosan. At the highest dose, SG-Gc also inhibited the paw edema induced by histamine (49%), compound 48/80 (32%), and phospholipase A(2) (44%). Sulfated galactan of G. crinale inhibited both neurogenic and inflammatory phases of the formalin test, at all doses, and at 10 mg/kg, the animals flinch reaction in the von Frey test in the 1st and 3rd h by 19 and 26%, respectively. Additionally, SG-Gc treatment was well tolerated by animals. In conclusion, SG-Gc presents anti-inflammatory effect involving the inhibition of histamine and arachidonic acid metabolites and also antinociceptive activity, especially the inflammatory pain with participation of the opioid system.

Changes in the suprachiasmatic nucleus during aging: implications for biological rhythms

Animals have neural structures that allow them to anticipate environmental changes and then regulate physiological and behavioral functions in response to these alterations. The suprachiasmatic nucleus of the hypothalamus (SCN) is the main circadian pacemaker in many mammalian species. This structure synchronizes the biological rhythm based on photic information that is transmitted to the SCN through the retinohypothalamic tract. The aging process changes the structural complexity of the nervous system, from individual nerve cells to global changes, including the atrophy of total gray matter. Aged animals show internal time disruptions caused by morphological and neurochemical changes in SCN components. The effects of aging on circadian rhythm range from effects on simple physiological functions to effects on complex cognitive performance, including many psychiatric disorders that influence the well-being of the elderly. In this review, we summarize the effects of aging on morphological, neurochemical, and circadian rhythmic functions coordinated by the main circadian pacemaker, the SCN.(AU)

Transplante multivisceral em suínos: modelo de pesquisa e treinamento / Multivisceral transplantation in pigs: a model for research and training

Objective: To present a model for research and training in multivisceral transplantation in pigs. Methods: Eight Large White pigs (four donors and four recipients) were operated. The multivisceral transplant with stomach, duodenum, pancreas, liver and intestine was performed similarly to transplantation in humans with a few differences, described below. Anastomoses were performed as follows: end-to-end from the supra-hepatic vena cava of the graft to the recipient juxta diaphragmatic vena cava; end-to-end from the infra-hepatic vena cava of the graft to the inferior (suprarenal) vena cava of the recipient; and endto- side patch of the aorta of the graft to the infrarenal aorta of the recipient plus digestive reconstruction. Results: The performance of the multivisceral transplantion was possible in all four animals. Reperfusions of the multivisceral graft led to a severe ischemia-reperfusion syndrome, despite flushing of the graft. The animals presented with hypotension and the need for high doses of vasoactive drugs, and all of them were sacrificed after discontinuing these drugs. Conclusion: Some alternatives to minimize the ischemia-reperfusion syndrome, such as the use of another vasoactive drug, use of a third pig merely for blood transfusion, presence of an anesthesia team in the operating room, and reduction of the graft, will be the next steps to enable experimental studies.

Objetivo: Apresentar um modelo de pesquisa e treinamento em transplante multivisceral em suínos. Métodos: Oito porcos da raça Large White (quatro doadores e quatro receptores) foram operados. O transplante multivisceral com estômago, duodeno, pâncreas, fígado e intestino foi realizado a semelhança do transplante em seres humanoscom algumas diferenças descritas a seguir. Foram realizadas as anastomoses de veia cava supra-hepática do enxerto com a veia cava do receptor justa diafragmática término-terminal, veia cava infrahepática do enxerto com a veia cava inferior (suprarrenal) do receptor término-terminal e patch da aorta do enxerto com a aorta infrarrenal do receptor término-lateral e reconstrução digestiva. Resultados: Foi possível a realização do transplante multivisceral nos quatro animais. A reperfusão do enxerto multivisceral levou a uma grave síndrome de isquemia-reperfusão, apesar do flush do enxerto. Os animais apresentaram hipotensão com necessidade de drogas vasoativas em altas doses, sendo todos sacrificados com a retirada dessas drogas. Conclusão: Alternativas para minimizar a síndrome de isquemiareperfusão, como o uso de mais de uma droga vasoativa, uso de um terceiro porco apenas para transfusão sanguínea, presença de umaequipe de anestesia na sala de cirurgia e redução do enxerto, serão os próximos passos para possibilitar estudos experimentais.

Multivisceral transplantation in pigs: a model for research and training.

OBJECTIVE: To present a model for research and training in multivisceral transplantation in pigs. METHODS: Eight Large White pigs (four donors and four recipients) were operated. The multivisceral transplant with stomach, duodenum, pancreas, liver and intestine was performed similarly to transplantation in humans with a few differences, described below. Anastomoses were performed as follows: end-to-end from the supra-hepatic vena cava of the graft to the recipient juxta diaphragmatic vena cava; end-to-end from the infra-hepatic vena cava of the graft to the inferior (suprarenal) vena cava of the recipient; and end-to-side patch of the aorta of the graft to the infrarenal aorta of the recipient plus digestive reconstruction. RESULTS: The performance of the multivisceral transplantion was possible in all four animals. Reperfusions of the multivisceral graft led to a severe ischemia-reperfusion syndrome, despite flushing of the graft. The animals presented with hypotension and the need for high doses of vasoactive drugs, and all of them were sacrificed after discontinuing these drugs. CONCLUSION: Some alternatives to minimize the ischemia-reperfusion syndrome, such as the use of another vasoactive drug, use of a third pig merely for blood transfusion, presence of an anesthesia team in the operating room, and reduction of the graft, will be the next steps to enable experimental studies.