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Image 1.

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Electrical stimulation (ES) of the nervous system is a promising alternative for the treatment of refractory epilepsy. Based on the understanding that seizures are the expression of neural hypersynchronism, our group developed and tested a non-standard form of low-energy temporally unstructured ES termed NPS (Non-periodic stimulation), with pseudo-randomized inter-pulse intervals. Previous investigation demonstrated that NPS applied to the amygdala has a robust anticonvulsant effect against both acute and chronic seizures, and suggested that its therapeutic effect is based on direct desynchronization of ictogenic neural circuits. Further mechanistic investigation using functional magnetic resonance imaging has shown that NPS also activates nucleus accumbens (NAc) in seizure-free rats, raising the hypothesis of an alternative therapeutic mechanism: NPS-enhanced indirect inhibition / desynchronization of ictogenic circuits by NAc. In order to investigate this idea, here we evaluated behavior and cortical electrographic activity from animals submitted to pentylenetetrazole (PTZ) induced seizures, treated with NPS and with or without bilateral electrolytic lesion of NAc. NPS-treated animals with bilateral lesion of NAc expressed unexpected straub tail in addition to other stereotypical convulsive behavior, displayed increased susceptibility to PTZ (lower drug threshold), and had a much longer electrographic seizure, with a greater number of spikes, firing at a higher rate. Moreover, analysis of spike morphology showed an increase in amplitude and slope in these animals, suggesting that ablation of NAc results in disinhibition and/or increase of neural synchronism within ictogenic circuits. NPS had no therapeutic effect whatsoever in lesioned animals, while it displayed a mild anticonvulsant effect in those with intact brains. Results corroborate the notion that NAc has a key role in controlling aberrant epileptiform activity in ictogenic circuits through indirect polysynaptic connections that may enroll the ventral pallidum and ventral tegmental area. They also point to the possibility that NPS may enhance this effect, putatively by benefiting from the structure's property of detecting saliences.

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A promising alternative for the treatment of refractory epilepsy is electrical stimulation (ES) of the central nervous system. Based on the premise that epilepsy is a result of neural hypersynchronization, we have previously demonstrated that a novel non-standard form of electrical stimulation with randomized inter-pulse intervals, termed non-periodic stimulation (NPS), applied to the amygdala is robustly anticonvulsant. This investigation also suggested that NPS attains its therapeutic effect by desynchronization of epileptiform activity. Here, we further explored the desynchronization hypothesis by testing how the efficacy of NPS in the suppression of convulsive behaviors depends on morphological, spatial, and temporal parameters of stimulus. For this purpose, we varied the number of pulse phases (monopolar versus bipolar square pulses), side of stimulation (right versus left), number of application hemispheres (unilateral versus bilateral), and interhemispheric temporal synchronicity (synchronous versus asynchronous), while measuring the impact on the anticonvulsant action of NPS. Wistar rats received a controlled infusion of the convulsant agent pentylenetetrazole (PTZ, 10 mg/min), together with one of six variations of NPS applied to the amygdala. A stimulated PTZ-free group of animals was also performed as a positive control. Latency to convulsive behavior was used to measure seizure threshold. Animals receiving NPS displayed significant higher threshold for forelimb clonus and generalized tonic-clonic seizures for all patterns. Thresholds seemed to increase gradually from mono to biphasic, unilateral to bilateral, and synchronous to asynchronous stimuli. Thus, combined biphasic, bilateral, and asynchronous stimulation resulted in the greatest seizure threshold. PTZ free animals did not develop any observable convulsive behavior or other uncommon motor activity. These results confirm that NPS has anticonvulsant properties and that biphasic, bilateral, and asynchronous stimulation enhances its efficacy. The fact that lack of synchronism between stimuli of each hemisphere maximizes NPS anticonvulsant power is evidence to desynchronization as tool for suppression of seizures.

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O Parque Nacional do Iguaçu é um dos últimos remanescentes de mata atlântica da região Sul, e por possuir as Cataratas do Iguaçu, com sua beleza exuberante, atrai anualmente mais de 1.000.000 de turistas, de vários países, que devido ao contato mais próximo com a natureza, possíveis vetores e potenciais hospedeiros se expõem a um risco de contrair patógenos. Dessa forma, esta pesquisa visou levantar a prevalência de filarioses em quatis (N. nasua) e cães domésticos no referido Parque. Foram capturados 75 quatis e 50 cães domésticos, posteriormente anestesiados com Zoletil® (5mg/kg) para colheita de amostras por punção jugular. Foram realizados o teste de Knott, sorológico para Dirofilaria immitis e histoquímica para identificação das microfilárias. O resultado do teste de concentração de Knott em quatis e cães domésticos demonstrou prevalência respectivamente de 81,6% e 17,7%, e total de cinco morfotipos identificados; no teste imunológico para Dirofilaria immitis, demonstrou-se prevalência de 1,29% em quatis e 22% em cães. A histoquímica das microfilárias dos quatis demonstrou a presença de sete padrões de marcação com prevalência de 1,29% para D.immitis, 10,6% para Dirofilaria repens e Acantocheilonema reconditum, 26,7% para os gêneros Mansonella sp. e 8% para Brugia sp, além de dois morfotipos não identificados. As três espécies identificadas infectando quatis no Parque Naci

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O Brasil é o país com maior diversidade de felinos selvagens do mundo, possuindo nove espécies descritas, entretanto pouco se conhece principalmente sobre os pequenos felinos. Atualmente todas as espécies de felinos neotropicais estão vulneráveis ou ameaçadas de extinção, e por isso surge a necessidade de se ampliar o conhecimento sobre a biologia e ecologia destas populações. Neste estudo, são descritos parasitas de uma fêmea de gato-maracajá (Leopardus wiedii), uma fêmea de gato-do-mato-pequeno (Leopardus guttulus) e um macho de jaguatirica (Leopardus pardalis) provenientes do ParNa Iguaçu, uma área prioritária para a conservação destas espécies in situ. Foi realizada a necrópsia parasitológica dos indivíduos, procedentes de atropelamento no Parna Iguaçu. Os órgãos foram seccionados, lavados e tamisados em busca de parasitas. Os helmintos recuperados foram armazenados em solução de Railliet & Henry, processados segundo técnicas de rotina e identificados morfologicamente em acordo com chaves taxonômicas. Como resultados obteve-se para L. wiedii os helmintos Molineus felineus e Taenia sp. no intestino delgado (ID) e Pearsonema pearsoni parasitando o rim. Para L. guttulus, formas imaturas de Ascarididae no estômago e fígado, Molineus felineus, Taenia sp. e Strongyloides stercoralis no ID. Para L. pardalis obteve-se Physaloptera praeputialis no estômago, Cestódeo não identif

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Os helmintos do gênero Mammomonogamus são parasitas do trato respiratório superior de mamíferos, sendo descritas onze espécies nos trópicos, com quatro destas registradas na região Neotropical. Geralmente, são encontrados parasitando ruminantes domésticos, cervídeos e felídeos nas Américas e búfalos, elefantes, rinocerontes e primatas no continente africano e sul asiático. Apesar de ser registrado em diversos hospedeiros, sua ocorrência é rara, com a maior parte dos estudos limitando-se apenas à citação do parasita no hospedeiro. Dessa forma, esta pesquisa visa descrever a ocorrência de exemplares de Mammomonogamus parasitando o trato respiratório de um veado-roxo (Mazama nemorivaga) proveniente da Guiana Francesa e apresentar as características morfológicas dessas espécies. Um indivíduo adulto de Mazama nemorivaga foi capturado e abatido por caçadores locais na região amazônica da Guiana Francesa para estudos taxonômicos e parasitológicos da espécie (autorização governo francês Arrêté nº 2014328-0018). À necropsia, foram observados nematódeos de coloração vermelho-viva na traqueia e faringe do hospedeiro. Estes nematódeos foram fixados e conservados em formalina a 10% até processamento em laboratório. Após processamento por técnicas de rotina, os espécimes foram identificados em acordo com chaves taxonômicas. Os nematódeos estudados foram identificados como M. nasicola (16 cas

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A Amazônia é o maior Bioma brasileiro, com uma das maiores biodiversidades mundiais, sendo o Pará o segundo maior estado inserido neste Bioma. Dentre as 167 espécies de morcegos descritas no Brasil, 120 foram registradas no Estado do Pará. Apesar da diversidade, são raros os estudos voltados para a descrição de helmintos em quirópteros pertencentes a este Bioma. Diante disso, o presente estudo tem como objetivo estudar os helmintos presentes em diferentes espécies de quirópteros pertencentes ao Bioma Amazônia. Foram utilizados 67 espécimes de morcegos pertencentes às famílias Phyllostomidae, Molossidae, Vespertilionidae e Natalidae provenientes da região Amazônica, mais especificamente do Estado do Pará, obtidos em capturas realizadas pelas Secretarias Municipais de Saúde e Centros de Controle de Zoonoses do Estado do Pará (CCZ) e encaminhados ao Laboratório de Raiva do Instituto Evandro Chagas. Os parasitas obtidos foram identificados taxonomicamente segundo chaves taxonômicas e os indicadores de infecção helmíntica foram calculados. Foram coletados no total de 182 espécimes de parasitas, sendo os resultados apresentados em prevalência, intensidade média e abundância média, de cestódeos foram identificados: 01 espécime de Hymenolepididae (1,49%; 1,00; 0,01); de trematódeos: 61 espécimes de Anenterotrema eduardocaballeroi (5,9%7; 15,25; 0,91), 79 de Anenterotrema liliputianum (

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O papagaio-verdadeiro (Amazona aestiva) está entre as aves silvestres mais encontradas em cativeiro. Papagaios de cativeiro possuem maior parasitismo devido ao confinamento aumentar a exposição a parasitas. A investigação parasitológica periódica em animais de reprodução é importante para manter o controle parasitário, evitando a disseminação e a possibilidade de interferência no desempenho reprodutivo, com a diminuição do fitness do hospedeiro. O objetivo deste estudo foi descrever ocorrência de doenças parasitárias em um criatório comercial de papagaio-verdadeiro, localizado em Jaboticabal-SP entre os anos de 2012 a 2014. Foram coletados excrementos de 60 papagaios designados à reprodução pertencentes a um criatório comercial em Jaboticabal-SP. Os animais são mantidos em viveiros e gaiolas alternadamente, alojados sempre aos pares. As amostras foram coletadas em períodos antecedentes à estação de reprodução entre anos de 2012 e 2014 e foram processados pelo método de Willis-Molay. A classe Cestoidea foi mais representativa durante os três anos estudados, entretanto no ano de 2014 teve o aparecimento de Capillaria e maior número de animais infectados por Eimeria spp, sendo que somente em 03 desses animais houve coinfecção entre cestódeos e Eimeria. Apenas um indivíduo não apresentou-se parasitado. Os coccídeos observados foram esporulados em solução de dicromato de potássio a

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O Brasil é o país com maior diversidade de felinos selvagens do mundo, possuindo nove espécies descritas, entretanto pouco se conhece principalmente sobre os pequenos felinos. Atualmente todas as espécies de felinos neotropicais estão vulneráveis ou ameaçadas de extinção, e por isso surge a necessidade de se ampliar o conhecimento sobre a biologia e ecologia destas populações. Neste estudo, são descritos parasitas de uma fêmea de gato-maracajá (Leopardus wiedii), uma fêmea de gato-do-mato-pequeno (Leopardus guttulus) e um macho de jaguatirica (Leopardus pardalis) provenientes do ParNa Iguaçu, uma área prioritária para a conservação destas espécies in situ. Foi realizada a necrópsia parasitológica dos indivíduos, procedentes de atropelamento no Parna Iguaçu. Os órgãos foram seccionados, lavados e tamisados em busca de parasitas. Os helmintos recuperados foram armazenados em solução de Railliet & Henry, processados segundo técnicas de rotina e identificados morfologicamente em acordo com chaves taxonômicas. Como resultados obteve-se para L. wiedii os helmintos Molineus felineus e Taenia sp. no intestino delgado (ID) e Pearsonema pearsoni parasitando o rim. Para L. guttulus, formas imaturas de Ascarididae no estômago e fígado, Molineus felineus, Taenia sp. e Strongyloides stercoralis no ID. Para L. pardalis obteve-se Physaloptera praeputialis no estômago, Cestódeo não identif

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A Amazônia é o maior Bioma brasileiro, com uma das maiores biodiversidades mundiais, sendo o Pará o segundo maior estado inserido neste Bioma. Dentre as 167 espécies de morcegos descritas no Brasil, 120 foram registradas no Estado do Pará. Apesar da diversidade, são raros os estudos voltados para a descrição de helmintos em quirópteros pertencentes a este Bioma. Diante disso, o presente estudo tem como objetivo estudar os helmintos presentes em diferentes espécies de quirópteros pertencentes ao Bioma Amazônia. Foram utilizados 67 espécimes de morcegos pertencentes às famílias Phyllostomidae, Molossidae, Vespertilionidae e Natalidae provenientes da região Amazônica, mais especificamente do Estado do Pará, obtidos em capturas realizadas pelas Secretarias Municipais de Saúde e Centros de Controle de Zoonoses do Estado do Pará (CCZ) e encaminhados ao Laboratório de Raiva do Instituto Evandro Chagas. Os parasitas obtidos foram identificados taxonomicamente segundo chaves taxonômicas e os indicadores de infecção helmíntica foram calculados. Foram coletados no total de 182 espécimes de parasitas, sendo os resultados apresentados em prevalência, intensidade média e abundância média, de cestódeos foram identificados: 01 espécime de Hymenolepididae (1,49%; 1,00; 0,01); de trematódeos: 61 espécimes de Anenterotrema eduardocaballeroi (5,9%7; 15,25; 0,91), 79 de Anenterotrema liliputianum (

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To identify an individual as familiar, rodents form a specific type of memory named social recognition memory. The olfactory bulb (OB) is an important structure for social recognition memory, while the hippocampus recruitment is still controversial. The present study was designed to elucidate the OB and the dorsal hippocampus contribution to the consolidation of social memory. For that purpose, we tested the effect of anisomycin (ANI), which one of the effects is the inhibition of protein synthesis, on the consolidation of social recognition memory. Swiss adult mice with cannulae implanted into the CA1 region of the dorsal hippocampus or into the OB were exposed to a juvenile during 5 min (training session; TR), and once again 1.5 h or 24 h later to test social short-term memory (S-STM) or social long-term memory (S-LTM), respectively. To study S-LTM consolidation, mice received intra-OB or intra-CA1 infusion of saline or ANI immediately, 3, 6 or 18 h after TR. ANI impaired S-LTM consolidation in the OB, when administered immediately or 6h after TR. In the dorsal hippocampus, ANI was amnesic only if administered 3 h after TR. Furthermore, the infusion of ANI in either OB or CA1, immediately after training, did not affect S-STM. Moreover, ANI administered into the OB did not alter the animal's performance in the buried food-finding task. Altogether, our results suggest the consolidation of S-LTM requires both OB and hippocampus participation, although in different time points. This study may help shedding light on the specific roles of the OB and dorsal hippocampus in social recognition memory.

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Impaired cholinergic neurotransmission can affect memory formation and influence sleep-wake cycles (SWC). In the present study, we describe the SWC in mice with a deficient vesicular acetylcholine transporter (VAChT) system, previously characterized as presenting reduced acetylcholine release and cognitive and behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to evaluate the SWC pattern during light and dark phases in VAChT knockdown heterozygous (VAChT-KDHET, n=7) and wild-type (WT, n=7) mice. SWC were evaluated for sleep efficiency, total amount and mean duration of slow-wave, intermediate and paradoxical sleep, as well as the number of awakenings from sleep. After recording SWC, contextual fear-conditioning tests were used as an acetylcholine-dependent learning paradigm. The results showed that sleep efficiency in VAChT-KDHET animals was similar to that of WT mice, but that the SWC was more fragmented. Fragmentation was characterized by an increase in the number of awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4±3.1 and 44.5±3.3 s for WT and VAChT-KDHET animals, respectively), which was followed by a 45% reduction in the number of paradoxical sleep episodes after the training session. Taken together, the results show that reduced cholinergic transmission led to sleep fragmentation and learning impairment. We discuss the results on the basis of cholinergic plasticity and its relevance to sleep homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders.

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Impaired cholinergic neurotransmission can affect memory formation and influence sleep-wake cycles (SWC). In the present study, we describe the SWC in mice with a deficient vesicular acetylcholine transporter (VAChT) system, previously characterized as presenting reduced acetylcholine release and cognitive and behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to evaluate the SWC pattern during light and dark phases in VAChT knockdown heterozygous (VAChT-KDHET, n=7) and wild-type (WT, n=7) mice. SWC were evaluated for sleep efficiency, total amount and mean duration of slow-wave, intermediate and paradoxical sleep, as well as the number of awakenings from sleep. After recording SWC, contextual fear-conditioning tests were used as an acetylcholine-dependent learning paradigm. The results showed that sleep efficiency in VAChT-KDHET animals was similar to that of WT mice, but that the SWC was more fragmented. Fragmentation was characterized by an increase in the number of awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4±3.1 and 44.5±3.3 s for WT and VAChT-KDHET animals, respectively), which was followed by a 45% reduction in the number of paradoxical sleep episodes after the training session. Taken together, the results show that reduced cholinergic transmission led to sleep fragmentation and learning impairment. We discuss the results on the basis of cholinergic plasticity and its relevance to sleep homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders.

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Epilepsy is a neurological disorder associated with excitatory and inhibitory imbalance within the underlying neural network. This study evaluated inhibitory γ-amino-butyric acid (GABA)ergic modulation in the CA1 region of the hippocampus of male Wistar rats and Wistar audiogenic rats (aged 90 ± 3 days), a strain of inbred animals susceptible to audiogenic seizures. Field excitatory postsynaptic potentials and population spike complexes in response to Schaffer collateral fiber stimulation were recorded in hippocampal slices before and during application of picrotoxin (50 µM, 60 min), a GABA A antagonist, and the size of the population spike was quantified by measuring its amplitude and slope. In control audiogenic-resistant Wistar rats (N = 9), picrotoxin significantly increased both the amplitude of the population spike by 51 ± 19 percent and its maximum slope by 73 ± 21 percent. In contrast, in slices from Wistar audiogenic rats (N = 6), picrotoxin caused no statistically significant change in population spike amplitude (33 ± 46 percent) or slope (11 ± 29 percent). Data are reported as means ± SEM. This result indicates a functional reduction of GABAergic neurotransmission in hippocampal slices from Wistar audiogenic rats.

Assuntos

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Epilepsy is a neurological disorder associated with excitatory and inhibitory imbalance within the underlying neural network. This study evaluated inhibitory γ-amino-butyric acid (GABA)ergic modulation in the CA1 region of the hippocampus of male Wistar rats and Wistar audiogenic rats (aged 90 ± 3 days), a strain of inbred animals susceptible to audiogenic seizures. Field excitatory postsynaptic potentials and population spike complexes in response to Schaffer collateral fiber stimulation were recorded in hippocampal slices before and during application of picrotoxin (50 µM, 60 min), a GABA A antagonist, and the size of the population spike was quantified by measuring its amplitude and slope. In control audiogenic-resistant Wistar rats (N = 9), picrotoxin significantly increased both the amplitude of the population spike by 51 ± 19% and its maximum slope by 73 ± 21%. In contrast, in slices from Wistar audiogenic rats (N = 6), picrotoxin caused no statistically significant change in population spike amplitude (33 ± 46%) or slope (11 ± 29%). Data are reported as means ± SEM. This result indicates a functional reduction of GABAergic neurotransmission in hippocampal slices from Wistar audiogenic rats.

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Several methods have been described to measure intraocular pressure (IOP) in clinical and research situations. However, the measurement of time varying IOP with high accuracy, mainly in situations that alter corneal properties, has not been reported until now. The present report describes a computerized system capable of recording the transitory variability of IOP, which is sufficiently sensitive to reliably measure ocular pulse peak-to-peak values. We also describe its characteristics and discuss its applicability to research and clinical studies. The device consists of a pressure transducer, a signal conditioning unit and an analog-to-digital converter coupled to a video acquisition board. A modified Cairns trabeculectomy was performed in 9 Oryctolagus cuniculus rabbits to obtain changes in IOP decay parameters and to evaluate the utility and sensitivity of the recording system. The device was effective for the study of kinetic parameters of IOP, such as decay pattern and ocular pulse waves due to cardiac and respiratory cycle rhythm. In addition, there was a significant increase of IOP versus time curve derivative when pre- and post-trabeculectomy recordings were compared. The present procedure excludes corneal thickness and error related to individual operator ability. Clinical complications due to saline infusion and pressure overload were not observed during biomicroscopic evaluation. Among the disadvantages of the procedure are the requirement of anesthesia and the use in acute recordings rather than chronic protocols. Finally, the method described may provide a reliable alternative for the study of ocular pressure dynamic alterations in man and may facilitate the investigation of the pathogenesis of glaucoma.

Assuntos

RESUMO

Several methods have been described to measure intraocular pressure (IOP) in clinical and research situations. However, the measurement of time varying IOP with high accuracy, mainly in situations that alter corneal properties, has not been reported until now. The present report describes a computerized system capable of recording the transitory variability of IOP, which is sufficiently sensitive to reliably measure ocular pulse peak-to-peak values. We also describe its characteristics and discuss its applicability to research and clinical studies. The device consists of a pressure transducer, a signal conditioning unit and an analog-to-digital converter coupled to a video acquisition board. A modified Cairns trabeculectomy was performed in 9 Oryctolagus cuniculus rabbits to obtain changes in IOP decay parameters and to evaluate the utility and sensitivity of the recording system. The device was effective for the study of kinetic parameters of IOP, such as decay pattern and ocular pulse waves due to cardiac and respiratory cycle rhythm. In addition, there was a significant increase of IOP versus time curve derivative when pre- and post-trabeculectomy recordings were compared. The present procedure excludes corneal thickness and error related to individual operator ability. Clinical complications due to saline infusion and pressure overload were not observed during biomicroscopic evaluation. Among the disadvantages of the procedure are the requirement of anesthesia and the use in acute recordings rather than chronic protocols. Finally, the method described may provide a reliable alternative for the study of ocular pressure dynamic alterations in man and may facilitate the investigation of the pathogenesis of glaucoma.

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The Wistar Audiogenic Rat (WAR) is a genetic model of reflex epilepsy with seizures induced by high-intensity sound stimulation (120 dB SPL). In spite of the known neural substrates involved in WAR seizure phenotype, neuroendocrine hypothalamic neurons were never investigated. In this work, AVP immunohistochemistry in the hypothalamus and radioimmunoassay (RIA) in plasma and in hypothalamic and hypophysial tissues were performed on both controls and WARs in order to evaluate the dynamics of AVP release due to seizure induction. Susceptible animals (WARs) displayed at least tonic-clonic convulsions followed by clonic spasms, while resistant Wistar rats (R) had no convulsive behavior. Animals were sacrificed at 3 instances: basal condition (without stimulus) and at 3 and 10 min after sound stimulation. For the immunohistochemistry AVP study, brains were harvested and processed by the avidin-biotin-peroxidase detection method. Optic densitometry was used for quantifying AVP labeling in supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei. SON presented higher densitometry levels (%D--relative to background) for both WARs and R when compared to PVN. Nevertheless, both nuclei presented a marked decrease, referenced to basal levels, in %D for WARs at 3 min (approximately 35%) against a discrete change for R (approximately 90%). RIA results were significantly higher in the hypophysis of WARs when compared to R rats, at 3 min. Also, at 3 min, plasma AVP in WARs (89.32 +/- 24.81 pg/mL) were higher than in R (12.01 +/- 2.39 pg/mL). We conclude, based on the AVP releasing profiles, that vasopressinergic hypothalamic neurons are recruited during the audiogenic seizure of WARs.

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Our hypothesis is that iron accumulated in tissue, rather than in serum, may compromise cardiovascular control. Male Fischer 344 rats weighing 180 to 220 g were divided into 2 groups. In the serum iron overload group (SIO, N = 12), 20 mg elemental iron was injected ip daily for 7 days. In the tissue iron overload group (TIO, N = 19), a smaller amount of elemental iron was injected (10 mg, daily) for 5 days followed by a resting period of 7 days. Reflex heart rate responses were elicited by iv injections of either phenylephrine (0.5 to 5.0 microg/kg) or sodium nitroprusside (1.0 to 10.0 microg/kg). Baroreflex curves were determined and fitted to sigmoidal equations and the baroreflex gain coefficient was evaluated. To evaluate the role of other than a direct effect of iron on tissue, acute treatment with the iron chelator deferoxamine (20 mg/kg, iv) was performed on the TIO group and the baroreflex was re-evaluated. At the end of the experiments, evaluation of iron levels in serum confirmed a pronounced overload for the SIO group (30-fold), in contrast to the TIO group (2-fold). Tissue levels of iron, however, were higher in the TIO group. The SIO protocol did not produce significant alterations in the baroreflex curve response, while the TIO protocol produced a nearly 2-fold increase in baroreflex gain (-4.34 +/- 0.74 and -7.93 +/- 1.08 bpm/mmHg, respectively). The TIO protocol animals treated with deferoxamine returned to sham levels of baroreflex gain (-3.7 +/- 0.3 sham vs -3.6 +/- 0.2 bpm/mmHg) 30 min after the injection. Our results indicate an effect of tissue iron overload on the enhancement of baroreflex sensitivity.

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Our hypothesis is that iron accumulated in tissue, rather than in serum, may compromise cardiovascular control. Male Fischer 344 rats weighing 180 to 220 g were divided into 2 groups. In the serum iron overload group (SIO, N = 12), 20 mg elemental iron was injected ip daily for 7 days. In the tissue iron overload group (TIO, N = 19), a smaller amount of elemental iron was injected (10 mg, daily) for 5 days followed by a resting period of 7 days. Reflex heart rate responses were elicited by iv injections of either phenylephrine (0.5 to 5.0 µg/kg) or sodium nitroprusside (1.0 to 10.0 µg/kg). Baroreflex curves were determined and fitted to sigmoidal equations and the baroreflex gain coefficient was evaluated. To evaluate the role of other than a direct effect of iron on tissue, acute treatment with the iron chelator deferoxamine (20 mg/kg, iv) was performed on the TIO group and the baroreflex was re-evaluated. At the end of the experiments, evaluation of iron levels in serum confirmed a pronounced overload for the SIO group (30-fold), in contrast to the TIO group (2-fold). Tissue levels of iron, however, were higher in the TIO group. The SIO protocol did not produce significant alterations in the baroreflex curve response, while the TIO protocol produced a nearly 2-fold increase in baroreflex gain (-4.34 ± 0.74 and -7.93 ± 1.08 bpm/mmHg, respectively). The TIO protocol animals treated with deferoxamine returned to sham levels of baroreflex gain (-3.7 ± 0.3 sham vs -3.6 ± 0.2 bpm/mmHg) 30 min after the injection. Our results indicate an effect of tissue iron overload on the enhancement of baroreflex sensitivity.

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