Ultrasound-guided Axillary Vein Puncture in Cardiac Lead Implantation: Time to Move to a New Standard Access?

Cardiac stimulation therapy has evolved significantly over the past 30 years. Currently, cardiac implantable electronic devices (CIED) are the mainstream therapy for many potentially lethal heart conditions, such as advanced atrioventricular block or sustained ventricular tachycardia or fibrillation. Despite sometimes being lifesaving, the implant is surgical and therefore carries all the inevitable intrinsic risks. In the process of technology evolution, one of the most important factors is to make it safer for the patient. In the context of CIED implants, complications include accidental puncture of intrathoracic structures. Alternative strategies to intrathoracic subclavian vein puncture include cephalic vein dissection or axillary vein puncture, which can be guided by fluoroscopy, venography or, more recently, ultrasound. In this article, the authors analyse the state of the art of ultrasound-guided axillary vein puncture using evidence from landmark studies in this field.

Transcatheter aortic valve implantation: results of the current development and implantation of a new Brazilian prosthesis.

OBJECTIVE: Aortic valve replacement is a routine procedure with acceptable risk, but in some cases, such risk can justify contraindication. Minimally invasive transcatheter aortic valve implantation has emerged as an alternative, with lower morbidity and mortality. The aim of this study was clinical, safety and efficacy assessment. METHODS: Thirty-three high risk patients underwent transcatheter balloon expandable aortic valve implantation. Mean Logistic EuroScore risk was 39.30% and STS score 30.28%. Eight patients presented with dysfunctional bioprosthesis, remaining ones presented calcified aortic stenosis. Procedures were performed in a hybrid OR under fluoroscopic and echocardiography guidance. Using a left minithoracotomy the prosthesis were implanted trough the ventricular apex under rapid ventricular pacing or hemorrhagic shock. Echocardiographic and angiographic controls were performed. RESULTS: Implant was feasible in 30 cases. Three conversions occured. There was only one case of operative death. Median transvalvular aortic gradient reduced from 43.58 mmHg to 10.54 mmHg. Left ventricular function improved in the first 7 postoperative days. Paravalvular aortic regurgitation was mild and present in 30.30%. One case presented major vascular complication and another one permanent pacemaker implant. One major stroke case occurred. Overall 30-day mortality was 18.18%. CONCLUSION: The transapical implantation of catheter mounted bioprosthesis is a safe procedure with acceptable midterm results. Long term follow-up with increased sample power is mandatory in order to access hemodynamic, life quality and survival.

Implante transcateter de valva aórtica: resultados atuais do desenvolvimento e implante de um nova prótese brasileira / Transcatheter aortic valve implantation: results of the current development and implantation of a new Brazilian prosthesis

OBJETIVO: A troca valvar aórtica é procedimento rotineiro com risco aceitável. Em alguns casos, a mortalidade é elevada, contraindicando o procedimento. O implante minimamente invasivo transcateter de valva aórtica parece ser alternativa, reduzindo a morbimortalidade. A avaliação dos resultados clínicos, segurança e eficácia do procedimento são o objetivo desse estudo. MÉTODOS: Uma prótese transcateter, balão expansível foi utilizada em 33 casos de alto risco. EuroScore médio foi de 39,30% e STS score de 30,28%. Oito pacientes apresentavam disfunção de bioprótese e o restante, estenose aórtica calcificada. Os procedimentos foram realizados em ambiente cirúrgico híbrido, sob controle ecocardiográfico e fluoroscópico. Através de minitoracotomia esquerda, as próteses foram implantadas pelo ápice ventricular, sob estimulação de alta frequência ou choque hemorrágico. Foram realizados controles clínicos e ecocardiográficos. RESULTADOS: A correta liberação da prótese foi possível em 30 casos. Três conversões ocorreram. A mortalidade operatória foi de um caso e a mortalidade em 30 dias, 18,18%. O gradiente médio reduziu de 43,58 para 10,54 mmHg. A fração de ejeção apresentou aumento significativo após o 7º pós-operatório. Insuficiência aórtica residual esteve presente em 30,30% dos pacientes. Ocorreu uma complicação vascular periférica e um caso de bloqueio atrioventricular total. Um paciente apresentou acidente vascular cerebral. A mortalidade em 30 dias foi de 18,18%. CONCLUSÃO: O implante transapical de valva aórtica transcateter é procedimento seguro e com resultados de médio prazo satisfatórios. São necessários estudos de longo prazo com maior poder amostral no intuito de determinar resultado hemodinâmico, qualidade de vida e sobrevida em longo prazo.

OBJECTIVE: Aortic valve replacement is a routine procedure with acceptable risk, but in some cases, such risk can justify contraindication. Minimally invasive transcatheter aortic valve implantation has emerged as an alternative, with lower morbidity and mortality. The aim of this study was clinical, safety and efficacy assessment. METHODS: Thirty-three high risk patients underwent transcatheter balloon expandable aortic valve implantation. Mean Logistic EuroScore risk was 39.30% and STS score 30.28%. Eight patients presented with dysfunctional bioprosthesis, remaining ones presented calcified aortic stenosis. Procedures were performed in a hybrid OR under fluoroscopic and echocardiography guidance. Using a left minithoracotomy the prosthesis were implanted trough the ventricular apex under rapid ventricular pacing or hemorrhagic shock. Echocardiographic and angiographic controls were performed. RESULTS: Implant was feasible in 30 cases. Three conversions occured. There was only one case of operative death. Median transvalvular aortic gradient reduced from 43.58 mmHg to 10.54 mmHg. Left ventricular function improved in the first 7 postoperative days. Paravalvular aortic regurgitation was mild and present in 30.30%. One case presented major vascular complication and another one permanent pacemaker implant. One major stroke case occurred. Overall 30-day mortality was 18.18%. CONCLUSION: The transapical implantation of catheter mounted bioprosthesis is a safe procedure with acceptable midterm results. Long term follow-up with increased sample power is mandatory in order to access hemodynamic, life quality and survival.

Uncovered stent does not provoke reactions in renal arteries and renal parenchyma in swines.

OBJECTIVE: To assess the histological changes of the aorta, the renal arteries and the renal parenchyma in swine, induced by a metalic uncovered stent implanted in transrenal position in the abdominal aorta. METHODS: Ten pigs with a mean weight of 86.6 kg and mean age of 6 months underwent implantation of metal stent graft placed in the aorta at the level of the renal arteries after 100 days of implantation. The self-expanding stents were released by laparotomy. Anatomic and histological analyses of the abdominal aorta, the renal arteries and the renal parenchyma were performed. Histological slices were performed in the following sites: 1) transitional zone between the aorta with and without stent graft; 2) portion of the renal arteries ostia; 3) renal parenchyma. The slices were stained through the hematoxylin and eosin stain technique and analyzed according the protocol of histological analyses applied in the clinical practice of pathology labs. RESULTS: The macroscopic findings showed thickening of the aortic wall; patent renal arteries; and normal anatomic renal structures. Microscopic analyses, close to the stents, showed thickening of the vascular wall, renal arteries without changes, and preserved renal parenchyma. CONCLUSION: The uncovered stainless steel stent caused a significant inflammatory reaction with thickening of the aortic wall. However, the renal arteries remained patent and the renal parenchyma did not present embolic or ischemic changes.

O stent descoberto não promove reações em artérias renais e parênquima renal em suínos / Uncovered stent does not provoke reactions in renal arteries and renal parenchyma in swines

OBJETIVO: Avaliar as alterações histológicas da aorta, artéria renal e parênquima renal, em suínos, induzidos pelo stent metálico descoberto implantado em localização transrenal na aorta abdominal. MÉTODOS: Foram utilizados 10 suínos com peso médio de 86,6 quilos e idade média de 6 meses, submetidos a implante de stent metálico posicionado na aorta, no nível das artérias renais, após 100 dias do implante. Os stents foram liberados por auto-expansão com laparotomia. Foram realizadas análises anatômicas e histológicas da aorta abdominal, artérias renais e parênquima renal. Os cortes histológicos foram realizados nos seguintes locais: 1) transição entre a aorta normal e aorta contendo stent; 2) porção contendo os óstios das artérias renais, 3) parênquima renal. As lâminas foram coradas pela técnica da hematoxilina e eosina e analisadas conforme protocolo de análise histológica aplicada na prática clínica dos laboratórios de patologia. RESULTADOS: Os achados macroscópicos revelaram espessamento da parede aórtica; artérias renais pérvias; estrutura anatômica renal normal. Análises microscópicas, próximas aos stents, evidenciaram espessamento da parede vascular, artérias renais sem alterações e parênquima renal preservado. CONCLUSÃO: O stent de aço inoxidável descoberto produziu importante reação inflamatória com espessamento da parede da aorta. No entanto, as artérias renais permaneceram pérvias e o parênquima renal sem alterações isquêmicas ou embólicas.

OBJECTIVE: To assess the histological changes of the aorta, the renal arteries and the renal parenchyma in swine, induced by a metalic uncovered stent implanted in transrenal position in the abdominal aorta. METHODS: Ten pigs with a mean weight of 86.6 kg and mean age of 6 months underwent implantation of metal stent graft placed in the aorta at the level of the renal arteries after 100 days of implantation. The self-expanding stents were released by laparotomy. Anatomic and histological analyses of the abdominal aorta, the renal arteries and the renal parenchyma were performed. Histological slices were performed in the following sites: 1) transitional zone between the aorta with and without stent graft; 2) portion of the renal arteries ostia; 3) renal parenchyma. The slices were stained through the hematoxylin and eosin stain technique and analyzed according the protocol of histological analyses applied in the clinical practice of pathology labs. RESULTS: The macroscopic findings showed thickening of the aortic wall; patent renal arteries; and normal anatomic renal structures. Microscopic analyses, close to the stents, showed thickening of the vascular wall, renal arteries without changes, and preserved renal parenchyma. CONCLUSION: The uncovered stainless steel stent caused a significant inflammatory reaction with thickening of the aortic wall. However, the renal arteries remained patent and the renal parenchyma did not present embolic or ischemic changes.

Efficacy of the combination of N-acetylcysteine and desferrioxamine in the prevention and treatment of gentamicin-induced acute renal failure in male Wistar rats.

BACKGROUND: Oxidative stress and the formation of aminoglycoside-iron complexes through iron-dependent Fenton reaction have been proposed to be the major mechanisms in the development of GM-induced acute renal failure (ARF); however, the efficacy of the combination of N-acetylcysteine (NAC) and desferrioxamine (DFX) in the prevention and the treatment of GM-induced ARF has not previously been investigated. METHODS: In the prevention protocol, adult male Wistar rats received gentamicin (GM) [70 mg/kg, intraperitoneally (i.p), each 12 h for 7 days], NAC (20 mg/kg, sc, each 8 h for 7 days) and/or DFX (20 mg/kg, sc, at first, fourth and seventh days). In the treatment protocol animals received GM for 7 days. Additionally, animals received NAC and or DFX starting in the fourth day after GM administration. Parameters of renal function had been evaluated 24 h, 4 and 8 days after the beginning of GM administration in the prevention protocol and in Days 5 and 8 in the treatment protocol. At the end of experiment, lipid peroxidation (TBARS assay) and protein oxidation (protein carbonyls levels) formation were evaluated in kidney tissue as oxidative damage parameters. RESULTS: In the prevention protocol, GM-induced ARF was prevented by the NAC and DFX association. Lipid peroxidation was attenuated by both antioxidant treatments, but the effects of NAC plus DFX were of greater magnitude. In the treatment protocol, plasma markers of renal injury were improved only in the NAC group, despite the similar antioxidant effect of both NAC, DFX and NAC plus DFX. CONCLUSION: Although the combination of NAC and DFX was more effective in the prevention protocol, the use of NAC alone seemed to be superior to NAC-DFX combination, in the treatment of GM-induced ARF in adult male Wistar rats.

Mangifera indica extract (Vimang) impairs aversive memory without affecting open field behaviour or habituation in rats.

Vimang is an aqueous extract of Mangifera indica L, used in Cuba for the treatment of immunopathological disorders. Increasing evidence from preclinical studies indicates that Vimang displays antioxidant, antiallergic, analgesic and antiinflammatory actions. The present study investigated the effects of systemic administration of Vimang on behavioural outcomes of neurological function in rats. A single oral administration of Vimang produced an impairment of short- and long-term retention of memory for aversive training when given either 1 h pretraining or immediately posttraining, but not 8 h posttraining. Vimang did not affect open field behaviour or habituation. The results indicate that Vimang might induce deficits of emotionally motivated memory without affecting nonassociative memory, locomotion, exploratory behaviour or anxiety.

Antioxidant treatment prevented late memory impairment in an animal model of sepsis.

OBJECTIVE: Assess the effect of antioxidant treatment on late memory impairment and early hippocampus oxidative stress after cecal ligation and perforation. SUBJECTS: Male Wistar rats. INTERVENTIONS: Rats underwent sham operation or cecal ligation and perforation. Animals that underwent cecal ligation and perforation were divided into groups: 1) treated with basic support (50 mL/kg saline, 30 mg/kg ceftriaxone, and 25 mg/kg clindamycin every 6 hrs), 2) treated with basic support plus N-acetylcysteine (20 mg/kg N-acetylcysteine at 3, 6, 12, 18, and 24 hrs after cecal ligation and perforation), 3) treated with basic support plus deferoxamine (20 mg/kg deferoxamine at 3 and 24 hrs after cecal ligation and perforation), 4) treated with basic support plus N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus deferoxamine. MEASUREMENTS AND MAIN RESULTS: On days 10 and 30 after surgery, the animals underwent behavioral tasks: inhibitory avoidance task, habituation to an open field, and continuous multiple-trials step-down inhibitory avoidance task. The sepsis group showed significantly decreased performance in latency retention compared with the sham group in the inhibitory avoidance task. In the open-field task, the sepsis group presented memory impairment after sepsis. In the continuous multiple-trials step-down inhibitory avoidance task, the sepsis group showed a significant increase in the number of training trials required to reach the acquisition criterion. All these memory impairments were prevented by N-acetylcysteine plus deferoxamine treatment, but not its isolate use. In addition, the combined use of antioxidants attenuated oxidative damage in hippocampus 6 hrs after sepsis induction. CONCLUSIONS: Antioxidant treatment prevented the development of late cognitive deficits in an animal model of sepsis.

A gastrin-releasing peptide receptor antagonist blocks D-amphetamine-induced hyperlocomotion and increases hippocampal NGF and BDNF levels in rats.

The gastrin-releasing peptide receptor (GRPR) has emerged as a novel molecular target in neurological and psychiatric disorders, and previous animal studies suggest that GRPR antagonists might display cognitive-enhancing and antipsychotic properties. Hyperlocomotion produced by administration of D-amphetamine (D-AMPH) to rats has been put forward as a model of the manic phase of bipolar disorder (BD). In the present study, we examined the effects of a single systemic administration of the GRPR antagonist [D-Tpi(6), Leu(13) psi(CH(2)NH)-Leu(14)] bombesin (6-14) (RC-3095) on hyperlocomotion induced by a single systemic injection of D-AMPH in male rats. We also evaluated the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus of rats treated with D-AMPH and RC-3095. Administration of RC-3095 at any of the doses used blocked D-AMPH-induced hyperlocomotion. Specific doses of RC-3095 increased the levels of NGF and BDNF in the dorsal hippocampus. Administration of D-AMPH did not affect NGF or BDNF levels by itself, but blocked the RC-3095 effects. The results suggest that GRPR antagonists might display anti-manic activity.

Lack of effect of dopaminergic antagonists in a rodent model of peritoneal sepsis.

Central nervous system dopaminergic mechanisms have been implicated in the cytokine response to stress and sepsis. We here describe the effects of haloperidol or clozapine in the treatment of sepsis induced by cecal ligation and puncture. Male Wistar rats were subjected to the CLP procedure were treated with haloperidol or clozapine and plasma cytokines, myeloperoxidase activity, markers of organ injury and survival was analyzed. The addition of haloperidol or clozapine to basic support did not diminished hepatic, renal, pancreatic or muscular damage observed after sepsis. Neither haloperidol, nor clozapine, modulates pro and antiinflammatory cytokines after sepsis induction. In addition, haloperidol treatment did not diminished myeloperoxidase activity in the kidney, lung or liver, or altered BALF markers of lung damage or inflammatory infiltration. Our data did not support a role of haloperidol or clozapine as an immunomodulator agent in the treatment of sepsis in an animal model of peritonitis.

Pharmacological activity of ruthenium complexes trans-[RuCl(2)(L)4] (l = nicotinic or i-nicotinic acid) on anxiety and memory in rats.

Many biological properties have been attributed to ruthenium complex I (trans-[RuCl(2)(nic)(4)]) and ruthenium complex II (trans-[RuCl(2 )(i-nic)( 4)]) including nitric oxide synthase inhibition. In this study, we evaluated pharmacological effects of these complexes on anxiety and memory formation. Memory was evaluated with inhibitory avoidance and habituation to an open-field and anxiety was tested with elevated plus-maze. Adult male Wistar rats (250 to 350 g) received intraperitoneal injections of vehicle, ruthenium complex I (45.2, 90.4, or 180.7 mumol/kg), or ruthenium complex II (0.08, 4.5, or 13.6 mumol/kg) 30 min prior open-field training or elevated plus-maze test and 30 min or 0 h after training. No effects were observed in the anxiety parameters and habituation to an open-field. The ruthenium complexes impaired memory retention compared with vehicle group in the inhibitory avoidance, as when administrated 30 min prior as immediately after training. The memory impairment induced by ruthenium complexes may be due to their nitric oxide synthase inhibition capacity.

Effects of milnacipran in animal models of anxiety and memory.

Serotonin (5-HT) and noradrenaline (NA) are involved in both pathogenesis and recovery from depression and anxiety. We examined the effects of acute and chronic treatment with milnacipran, a serotonin/noradrenaline reuptake inhibitors (SNRIs) antidepressant, on anxiety and memory retention in rats. Male Wistar rats received acute or chronic administration of milnacipran (12.5, 25 or 50 mg/kg) or saline (control group). The animals were separately submitted to elevated plus-maze, inhibitory avoidance and open-field tasks 1 h after injection, in the acute group, or 23 h after last injection, in the chronic group. Our results showed an anxiolytic-like effect after chronic administration of milnacipran at doses of 25 and 50 mg/kg. The treatment does not interfere in memory retention and habituation to a novel environment at any doses studied. These findings support that milnacipran, an established SNRIs antidepressant, can also be useful in the treatment of anxiety disorders.

Reação histopatológica da parede da aorta abdominal ao stent não recoberto / Histopathological reaction of the abdominal aorta wall to non-covered stents

OBJETIVO: Avaliar a reação histopatológica da parede aorta abdominal, em suínos, no nível das artérias renais, na presença de stent metálico não recoberto. MÉTODO: Foi estudada histopatologicamente a aorta abdominal de 10 suínos, com peso médio de 86,6 quilos e idade média de 6 meses, submetidos a implante de stent metálico posicionado na aorta, no nível das artérias renais, após 100 dias do implante. Os stents foram liberados por auto-expansão com laparotomia. Os cortes histológicos foram realizados nos seguintes locais: 1) transição entre a aorta normal e aorta contendo stent; 2) aorta contendo o stent; 3) porção contendo os óstios das artérias renais, 4) linfonodos periaórticos e, 5) parênquima renal. As lâminas foram coradas pela técnica da hematoxilina e eosina. RESULTADOS: Os achados macroscópicos revelaram: linfonodomegalia periaórtica; espessamento da parede aórtica; artérias lombares e renais pérvias; estrutura anatômica renal normal. Análises microscópicas, próximas aos stents, evidenciaram espessamento da parede vascular, secundário à fibrose intimal e camada média comprometida com fibrose intersticial. Medidas micrométricas da parede aórtica com o stent, comparada à aorta sem o stent, apresentaram aumento da espessura da parede (75,9 por cento) por hiperplasia da camada íntima secundária à proliferação de fibroblastos; depósitos de colágeno com infiltrado inflamatório e granulomas do tipo corpo estranho. CONCLUSÃO: O stent de aço inoxidável descoberto, implantado na aorta de suínos, produziu importante reação inflamatória, com fibrose nas camadas média e íntima, evidenciada pelas análises histopatológicas e a sua presença não comprometeu o estado pérvio da aorta e dos ramos lombares e renais.

OBJECTIVE: To evaluate the histopathological reaction of the abdominal aorta wall in pigs' renal arteries to the presence of non-covered stainless steel stents. METHODS: The abdominal aorta of ten pigs (6 months old and weighing 86.6 kg on average) was histopathologically studied 100 days after the implant to a stainless steel stents in the abdominal aorta, with one segment of the stent inplanted in the renal artery. Self-expanding non-covered stents were released by laparotomy. The histological slices were made at the transition from the normal aorta and the aorta containing the stent; the aorta portion containing the stent; the portion with the ostia of renal arteries; periaortic lymph nodes and renal parenchyma. The samples were stained by hematoxylin and eosin technique. RESULTS: Macroscopic findings showed periaortic lymphadenopathy, thickened aortic wall, patency of lumbar and renal arteries and normal renal anatomical structure. Microscopic analyses near the stents revealed thickening of vessel wall, secondary to the intima fibrosis, and media layer affected by interstitial fibrosis. Micrometric measurements of aorta wall with the stent, compared to the aortic portion without it, presented a 75.90 percent increasein the total thickness of the wall by thickening of the intima layer secondary to fibroblast proliferation, collagen deposits with lymphocitary inflammatory infiltrate and foreign body-type granulomas. CONCLUSION: The non-covered stainless steel stent in pigs' aortas produced a significant inflammatory reaction with fibrosis in the media and intima layers evidenced by histopathological analyses; their presence did not interfere in the patency of the abdominal aorta or the renal and lumbar arteries.

Increased oxidative stress after repeated amphetamine exposure: possible relevance as a model of mania.

BACKGROUND: Acute mania can be modeled in animals using D-amphetamine (AMPH). Acute AMPH injections are associated with monoamine depletion, loss of neurofilaments and neurite degeneration. However, the precise mechanisms underlying AMPH-induced neurotoxicity are still unclear. Several studies have demonstrated that oxidative stress may play a role in the behavioral and neurochemical changes observed after AMPH administration. METHODS: The effects of a single and repeated injections (seven daily injections) of AMPH administered intraperitonially on locomotion and the production of lipid and protein oxidative markers in rat cortex, striatum and hippocampus were assessed. Locomotion was assessed in an open-field task and markers of oxidative stress were assessed in brain tissue. RESULTS: Both single and repeated injections of AMPH increased protein carbonyl formation in rat brain. Repeated exposure to AMPH induced an additional increase in thiobarbituric acid reactive species in brain tissue. CONCLUSIONS: Longer periods of exposure to AMPH were associated with increased oxidative stress in rat brain. This adds to the notion that repeated manic episodes may be associated with greater brain damage and, therefore, poorer outcomes.

Gastrin-releasing peptide receptor antagonist effects on an animal model of sepsis.

RATIONALE: Several new therapeutic strategies have been described for the treatment of sepsis, but to date none are related to alterations in the bombesin/gastrin-releasing peptide (GRP) receptor pathways. OBJECTIVES: To determine the effects of a selective GRP receptor antagonist, RC-3095, on cytokine release from macrophages and its in vivo effects in the cecal ligation and puncture (CLP) model of sepsis and in acute lung injury induced by intratracheal instillation of LPS. METHODS: We determined the effects of RC-3095 in the CLP model of sepsis and in acute lung injury induced by intratracheal instillation of LPS. In addition, we determined the effects of RC-3095 on tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, and nitric oxide release from activated macrophages. MEASUREMENTS AND MAIN RESULTS: The GRP antagonist attenuated LPS- or CLP-induced TNF-alpha, IL-1beta, and nitric oxide release in cultured macrophages and decreased the mRNA levels of inducible nitric oxide synthase. The administration of RC-3095 (0.3 mg/kg) 6 h after sepsis induction improved survival in the CLP model, and diminished lung damage after intratracheal instillation of LPS. These effects were associated with attenuation on the circulating TNF-alpha and IL-1beta levels and decreased myeloperoxidase activity in several organs. CONCLUSIONS: We report that a selective GRP receptor antagonist attenuates the release of proinflammatory cytokines in vitro and in vivo and improves survival in "established" sepsis. These are consistent with the involvement of a new inflammatory pathway relevant to the development of sepsis.

Non-associative learning and anxiety in rats treated with a single systemic administration of the gastrin-releasing peptide receptor antagonist RC-3095.

The gastrin-releasing peptide receptor (GRPR) has been implicated in the modulation of emotionally-motivated memory. In the present study, we investigated the role of the GRPR on non-emotional, non-associative memory, and anxiety. Adult male Wistar rats were given a systemic injection of the GRPR antagonist [D-Tpi6, Leu(13) psi(CH2NH)-Leu14] bombesin (6-14) (RC-3095) (0.2, 1.0 or 5.0mg/kg) 30 min before exposure to an open field or an elevated plus maze. Habituation to the open field was tested in a retention trial carried out 24 h after the first exposure to the open field. Rats given RC-3095 at the doses of 1.0 or 5.0mg/kg showed impaired habituation. Animals treated with 5.0mg/kg of RC-3095 spent significantly more time in the closed arms of the elevated plus maze. No effects of RC-3095 on locomotion or exploratory behavior were observed. The results implicate the GRPR in the regulation of non-emotional, non-associative memory as well as in anxiety.

Short- and long-term memory are differentialy modulated by hippocampal nerve growth factor and fibroblast growth factor.

Rats were implanted with cannulae in the CA1 area of the dorsal hippocampus and trained in one-trial step-down inhibitory avoidance. Two retention tests were carried out in each animal, one at 1.5 h to measure short-term memory (STM) and another at 24 h to measure long-term memory (LTM). The purpose of the present study was to evaluate the modulation on hippocampal nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) on short- and long-term memory. Immediately after training, animals received 5 microl of NGF (0.05, 0.5 or 5.0 ng), bFGF (1.25, 12.5 or 125 ng) or saline per side. At the higher dose, NGF blocked STM. In contrast, NGF at dose of 0.5 and 5.0 ng improved LTM. The bFGF infusion at a dose of 125 ng enhanced LTM. However, bFGF did not alter STM. These findings indicate that hippocampal NGF and bFGF modulate STM and LTM in a different manner.

Pretraining but not preexposure to the task apparatus prevents the memory impairment induced by blockade of protein synthesis, PKA or MAP kinase in rats.

Adult male Wistar rats were trained and tested in a step-down inhibitory avoidance task (0.4 mA footshock, 24 h training-test interval). Fifteen minutes before or 0, 1.5 or 3 hours after training, animals received a 0.8 microl intrahippocampal infusion of the protein synthesis inhibitor anisomycin (80 microg), the PKA inhibitor Rp-cAMP (0.05 microg), the MAPK kinase inhibitor PD 098059 (50 microM solution) or vehicle (phosphate buffer in saline, pH 7.4). Anisomycin, Rp-cAMP and PD 098059 impaired retention test performance in animals injected at different times, prior and after training. Pretraining with a low footshock intensity (0.2 mA) 24 h before training prevented the amnestic effect of all drugs studied. However, simple preexposure to the inhibitory avoidance apparatus did not alter the amnestic effects of all drugs. The results suggest that memory processing requires hippocampal mechanisms dependent on protein synthesis, PKA and MAPK kinase at different times after training. These findings suggest that weak training must be sufficient to produce some lasting cellular expression of the experience so that the enhancement of consolidation of a previously acquired memory is not dependent on protein synthesis, PKA or MAPK.

Haloperidol and clozapine, but not olanzapine, induces oxidative stress in rat brain.

Typical and atypical antipsychotic drugs have been shown to have different clinical and behavioral profiles. Haloperidol (HAL) is a typical neuroleptic that acts primarily as a D2 dopamine receptor antagonist. It has been proposed that reactive oxygen species play a causative role in neurotoxic effects induced by HAL. We evaluated oxidative damage in rat brain induced by chronic HAL, clozapine (CLO) or olanzapine (OLZ) administration. Adult male Wistar rats received daily injections of Hal (1.5mg/kg), CLO (25mg/kg) or OLZ (2.5, 5.0 or 10.0mg/kg). Control animals were given saline (SAL; NaCl 0.9%). Thiobarbituric acid reactive substances (TBARS) and protein carbonylation were measured in the hippocampus (HP), striatum (ST) and cortex (CX). TBARS was increased in the striatum after HAL treatment. In contrast, there was a decrease of TBARS levels induced by HAL, CLO and OLZ treatments in the cortex. Protein carbonyls after HAL and CLO treatment was increased in the hippocampus, compared to control. In hippocampus, OLZ did not show significant difference to control in both oxidative parameters. Our findings demonstrated that atypical antipsychotic CLO produced less oxidative damage than HAL and we did not find oxidative damage induced by OLZ.