RESUMO
Understanding the risks of a developing unconventional hydrocarbons industry, including shale gas, to the chemical quality of surface water and groundwater involves firstly establishing baseline compositions against which any future changes can be assessed. Contaminants of geogenic origin are of particular interest and radon has been identified as one potential contaminant from shale sources. Robust measurement and monitoring of radon in water at environmental concentrations is essential for ensuring protection of water sources and maintaining public confidence. Traditional techniques for Rn-222 determination in water, such as inference by gamma spectrometry and direct alpha counting, are impractical for direct field measurement, and the relatively short half-life of Rn-222 (~ 3.82 days) means that longer analytical protocols from field to the laboratory may result in greater uncertainty for Rn-222 activity. Therefore, a rapid and low-cost method would be beneficial. We have developed and refined a laboratory procedure for Rn-222 monitoring using liquid scintillation counting (LSC). The accuracy of Rn-222 activities obtained via this procedure was evaluated by the analysis of almost 200 water samples collected from streams and boreholes as part of a detailed baseline investigation in the Vale of Pickering, Yorkshire, one potential location for future shale gas exploration. LSC was preferred for measurement of Rn-222 and had comparable accuracy to gamma spectrometry and direct alpha counting. The methodology provided a rapid, portable and low-maintenance option relative to the two established techniques and is shown to be a favourable choice for the measurement of radon in surface water and groundwater at environmental concentrations.
Assuntos
Água Doce/análise , Radônio/análise , Contagem de Cintilação/métodos , Poluentes Radioativos da Água/análise , Água Subterrânea/análise , Monitoramento de Radiação , Rios , Espectrometria gama/métodos , Reino UnidoRESUMO
Canine cutaneous mast cell tumor (MCT) is the most common canine skin tumor and exhibits variable biologic behavior. Signaling through the KIT receptor tyrosine kinase promotes cellular proliferation and survival and has been shown to play a role in MCT progression. Despite investigations into numerous biomarkers and the proposal of several grading schemas, no single marker or grading system can accurately predict outcome in canine MCT. The first aim of this study was to develop an immunohistochemical assay to measure phosphorylated KIT (pKIT) to investigate its association with 2 commonly used grading systems and other established prognostic markers for canine MCT. Thirty-four archived MCTs were evaluated for expression of pKIT and Ki-67, KIT localization, mitotic count, mutations in exons 8 and 11 in c-kit, and grading by the Patnaik and 2-tier systems. Expression of pKIT was significantly ( P < .05) correlated with the 2-tier grading scheme and c-kit mutation. Correlation approached significance ( P = .06) with Mitotic Index (MI) and Ki-67. An additional aim was to determine whether pKIT labeling provides a pharmacodynamic marker for predicting response to the receptor tyrosine kinase inhibitor toceranib (TOC). MCTs from 4 of 7 patients demonstrated a partial response to TOC. pKIT expression was assessed by immunohistochemistry in biopsies obtained before and 6 hours after the patients were treated with TOC. Reduced pKIT expression after TOC treatment was demonstrated in 3 of the 4 patients with a partial response compared to 1 of the 3 nonresponders. Collectively, these results demonstrate that immunohistochemical detection of pKIT may be a clinically relevant assay to evaluate the activation status of the major oncogenic pathway in canine MCT.
Assuntos
Doenças do Cão/patologia , Mastocitose Cutânea/veterinária , Proteínas Proto-Oncogênicas c-kit/metabolismo , Animais , Biomarcadores , Doenças do Cão/diagnóstico , Cães , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/patologia , Fosforilação , Prognóstico , Estudos RetrospectivosRESUMO
Immunohistochemistry allows the localization of proteins to specific regions of the nephron. This article reports the identification and localization of proteins in situ within normal canine, feline, and mouse kidney by immunohistochemistry; maps their distribution; and compares results to previously reported findings in other species. The proteins investigated are aquaporin 1, aquaporin 2, calbindin D-28k, glutathione S-transferase-α, and Tamm-Horsfall protein. Aquaporins are integral membrane proteins involved in water transport across cell membranes. Calbindin D-28k is involved in renal calcium metabolism. Glutathione S-transferase-α is a protein that aids in detoxification and drug metabolism. The role of Tamm-Horsfall protein is not fully understood. Proposed functions include inhibition of calcium crystallization and reduction of bacterial urinary tract infection. The authors' findings in the dog are similar to those in other species: Specifically, the authors localize aquaporin 1 to the proximal convoluted tubule epithelium, vasa recta endothelium, and descending thin limbs; aquaporin 2 to collecting duct epithelium; and calbindin D-28k within distal convoluted tubule epithelium. Glutathione S-transferase-α has variable expression and is found in only the renal transitional epithelium in some individuals, in only the proximal straight tubules in others, or in both locations in others. Tamm-Horsfall protein localizes to thick ascending limb epithelium. These findings are similar in the cat, with the exception that aquaporin 1 is located in glomerular podocytes, in addition to proximal convoluted tubule epithelium, and glutathione S-transferase-α is found solely within the proximal convoluted tubule within all kidney samples examined. The mouse kidney is almost identical to the dog but expresses glutathione S-transferase-α in the glomeruli only.
Assuntos
Gatos/fisiologia , Cães/fisiologia , Rim/metabolismo , Proteínas de Membrana/metabolismo , Camundongos/fisiologia , Transporte Proteico/fisiologia , Animais , Regulação da Expressão Gênica/fisiologia , Proteínas de Membrana/genéticaRESUMO
Lymphoma in the left femoral nerve of a 10-year-old English Cocker Spaniel caused complete paralysis of the affected limb. Neoplastic cells were immunopositive for CD79a and Pax5 and negative for CD3. Neoplastic cells were in multiple lymph nodes and one kidney but spared bone marrow. The clinical and histologic features in this case resemble those of the rare human condition of neurolymphomatosis.
Assuntos
Doenças do Cão/diagnóstico , Nervo Femoral/patologia , Linfoma de Células B/veterinária , Doenças do Sistema Nervoso Periférico/veterinária , Animais , Antígenos CD79/imunologia , Diagnóstico Diferencial , Doenças do Cão/imunologia , Doenças do Cão/patologia , Cães , Extremidades/patologia , Evolução Fatal , Feminino , Artéria Femoral/patologia , Imuno-Histoquímica/veterinária , Imunofenotipagem/veterinária , Rim/patologia , Linfonodos/imunologia , Linfonodos/patologia , Linfoma de Células B/diagnóstico , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Células Neoplásicas Circulantes/patologia , Fator de Transcrição PAX5/imunologia , Paralisia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/imunologia , Doenças do Sistema Nervoso Periférico/patologiaRESUMO
River islands (Ait or Eyot) within the inner tidal Thames serve as unique recorders of current and historical estuarine chemical pollution. Sediment cores from Chiswick Ait were assessed for contamination using Microtox® solid phase bioassay, stable isotopes (δ13C, δ15N), heavy metals and polychlorinated biphenyls (PCBs). Microtox® classified these sediments as non-toxic to moderately toxic and bulk isotopes identified a change in organic input. Metals Cu, Zn, Cr, Ni, Cd, Hg and Ag showed parallel rise, peak and fall profiles which when allied to a 207/208Pb and 137Cs based chronology supported major changes in trace metal contributions corresponding to approximate input times of 1940 (rise), 1963 (peak) and 1985 (fall). Metals ranged from Cu 15 to 373 mg kg-1 (mean 141 mg kg-1), Zn 137 to 1331 mg kg-1 (mean 576 mg kg-1), Cr 14-351 mg kg-1 (mean 156 mg kg-1), Pb 10 to 1506 mg kg-1 (mean 402 mg kg-1), As 1 to 107 (mean 38 mg kg-1), Ni 11 to 113 mg kg-1 (mean 63 mg kg-1), Cd 0.2 to 53 mg kg-1 (mean 9 mg kg-1), Hg 1 to 8 mg kg-1 (mean 4.6 mg kg-1) and Ag from 0.7 to 50 mg kg-1 (mean 7.5 mg kg-1). Down core total PCBs ranged from 10.5 to 121 µg kg-1 and mean of 39 µg kg-1. The rise, peak and fall of Cu, Zn, Cr, Ni, Cd and Ag pollution matched local sewage works' treatment discharge records. Whereas the Hg, Pb and As profiles were disconnected, reflecting alternative historic sources and or partitioning behaviour. Comparison to marine sediment quality guidelines indicate that Zn, Pb, Ni, Cd and Hg exceed action level 2, whereas sedimentary Cu, Cr and As concentrations were above action level 1 (no action) but below action level 2 (further investigation required). The river islands of the tidal Thames capture a unique contaminant chemistry record due in part to their location in the tidal frame (salinity minimum) and close proximity to west London.
Assuntos
Metais Pesados , Bifenilos Policlorados , Poluentes Químicos da Água , China , Monitoramento Ambiental , Estuários , Sedimentos Geológicos , Londres , Metais Pesados/toxicidade , Bifenilos Policlorados/toxicidade , Rios , Poluentes Químicos da Água/toxicidadeRESUMO
Since the publication of the Society for Immunotherapy of Cancer's (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in the field is the fact that only a minority of patients respond to immunotherapy, especially those therapies that rely on endogenous immune activation such as checkpoint inhibitors and vaccination due to the complex and heterogeneous immune escape mechanisms which can develop in each patient. Therefore, the development of robust biomarkers for each immunotherapy strategy, enabling rational patient selection and the design of precise combination therapies, is key for the continued success and improvement of immunotherapy. In this document, we summarize and update established biomarkers, guidelines, and regulatory considerations for clinical immune biomarker development, discuss well-known and novel technologies for biomarker discovery and validation, and provide tools and resources that can be used by the biomarker research community to facilitate the continued development of immuno-oncology and aid in the goal of durable responses in all patients.
Assuntos
Biomarcadores Tumorais/imunologia , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , HumanosRESUMO
BACKGROUND: Survivin, a member of the inhibitor of apoptosis protein family, has a dual role in tumor cell proliferative and antiapoptotic pathways. Survivin expression has been shown to be a negative prognostic factor in several cancers of humans, including B-cell non-Hodgkin's lymphoma. HYPOTHESES: High survivin expression will be a negative prognostic factor in dogs with lymphoma (LSA) treated with chemotherapy. In addition, survivin expression will be upregulated in relapsed canine LSA when compared with patient-matched, pretreatment biopsies. ANIMALS: Thirty-one client-owned dogs with stage IIIa or IVa LSA. METHODS: Retrospective evaluation of survivin immunoreactivity was performed on pretreatment lymph node biopsies and patient-matched samples obtained from dogs at relapse after being treated with an abbreviated CHOP-based protocol. RESULTS: In this population of dogs presenting with stage IIIa or IVa B-cell LSA, those dogs that had high survivin immunoreactivity scores had a significantly (P < .01, hazard ratio = 0.30) shorter median disease-free interval than did dogs with low survivin immunoreactivity scores (171 days versus 321 days, respectively). Survivin immunoreactivity was not significantly different in relapsed canine LSA when compared with patient-matched, pretreatment biopsies. CONCLUSIONS AND CLINICAL IMPORTANCE: Survivin expression is a negative prognostic factor that can predict early treatment failure of dogs that present with stage IIIa or IVa, B-cell LSA when treated with a CHOP-based protocol.
Assuntos
Doenças do Cão/metabolismo , Linfoma/veterinária , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Neoplasias/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doenças do Cão/tratamento farmacológico , Cães , Doxorrubicina/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica , Linfoma/tratamento farmacológico , Linfoma/metabolismo , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas de Neoplasias/genética , Prednisona/uso terapêutico , Recidiva , Fatores de Tempo , Vincristina/uso terapêuticoRESUMO
BACKGROUND: KIT inhibitors, such as toceranib (TOC), and vinblastine (VBL) have not been prospectively compared in the treatment of macroscopic mast cell tumors (MCTs). Also, it is unknown whether VBL or TOC is superior for treating MCT without c-kit mutations. HYPOTHESIS/OBJECTIVES: To determine the value of KIT genotyping and localization in treatment decisions for dogs with macroscopic MCT. We hypothesized that c-kit mutated MCT would have a better response to TOC than VBL. ANIMALS: Eighty-eight client-owned dogs with macroscopic MCT. METHODS: Prospective, randomized trial. Dogs were randomized to TOC (2.75 mg/kg EOD) or VBL (2.5 mg/m2 weekly × 4 then EOW) by KIT localization and c-kit mutation status using an adaptive randomization scheme. RESULTS: Sixty dogs were allocated to TOC and 28 to VBL. Of the dogs receiving TOC, 20% had c-kit mutations, compared to 30% receiving VBL (P = 0.74). Overall response rates were 46% (TOC) and 30% (VBL) (odds ratio = 1.56 [0.62-3.92]; P = 0.28). Median progression-free survival (PFS) for dogs receiving VBL was 78 days (7-1,521) and for TOC 95.5 (14-990); hazard ratio (HR) = 1.34 [0.72-2.50]; P = 0.36. Median overall survival (OS) was 241.5 days (10-1,521) for the VBL group and 159 (20-990) for the TOC group; HR = 0.80 ([0.45-1.41]; P = 0.44). CONCLUSIONS AND CLINICAL IMPORTANCE: Neither PFS nor OS was significantly different between treatment groups. As the proportion of dogs with c-kit mutations was not different between treatment groups in this population of dogs, c-kit mutation status did not predict treatment response.
Assuntos
Doenças do Cão/tratamento farmacológico , Indóis/uso terapêutico , Mastocitose Cutânea/veterinária , Prednisona/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Pirróis/uso terapêutico , Vimblastina/uso terapêutico , Animais , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Cães , Feminino , Masculino , Mastocitose Cutânea/tratamento farmacológico , Mastocitose Cutânea/genética , Mutação , Estudos ProspectivosRESUMO
Canine lymphoma (LSA) and osteosarcoma (OS) have high mortality rates and remain in need of more effective therapeutic approaches. Survivin, an inhibitor of apoptosis (IAP) family member protein that inhibits apoptosis and drives cell proliferation, is commonly elevated in human and canine cancer. Survivin expression is a negative prognostic factor in dogs with LSA and OS, and canine LSA and OS cell lines express high levels of survivin. In this study, we demonstrate that survivin downregulation in canine LSA and OS cells using a clinically applicable locked nucleic acid antisense oligonucleotide (EZN-3042, Enzon Pharmaceuticals, Piscataway Township, NJ, USA) inhibits growth, induces apoptosis and enhances chemosensitivity in vitro, and inhibits survivin transcription and protein production in orthotopic canine OS xenografts. Our findings strongly suggest that survivin-directed therapies might be effective in treatment of canine LSA and OS and support evaluation of EZN-3042 in dogs with cancer.
Assuntos
Apoptose/efeitos dos fármacos , Doenças do Cão/metabolismo , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Linfoma/veterinária , Oligonucleotídeos/farmacologia , Osteossarcoma/veterinária , Animais , Linhagem Celular Tumoral , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Inibidoras de Apoptose/metabolismo , Linfoma/tratamento farmacológico , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Lymphangiosarcomas are uncommon vascular neoplasms that arise from lymphatic endothelial cells (LECs). They efface and replace normal subcutaneous tissue and are characterised by arborising, vascular channels lined by a single layer of pleomorphic endothelial cells and a paucity of erythrocytes. Lymphangiosarcomas are architecturally similar to hemangiosarcomas, a common malignancy of vascular origin arising from blood vascular endothelial cells. Common immunohistochemical markers for vascular endothelium, such as Factor VIII-related antigen (F8RA) and CD31, have traditionally been used to confirm the diagnosis of tumours of vascular origin. However, these markers fail to differentiate between lymphangiosarcoma and hemangiosarcoma, which often show overlapping morphologic features, disparate clinical behaviour and require different treatment modalities. Here we describe the use of two novel LEC-specific markers, lymphatic vessel endothelial receptor-1 (LYVE-1) and prospero-related homeobox gene-1 (PROX-1), to further differentiate between vascular tumours of lymphatic (lymphangiosarcoma) and blood (hemangiosarcoma) endothelial cell origin in the dog.
Assuntos
Doenças do Cão/classificação , Células Endoteliais/metabolismo , Hemangiossarcoma/veterinária , Proteínas de Homeodomínio/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Neoplasias Vasculares/veterinária , Proteínas de Transporte Vesicular/metabolismo , Animais , Anticorpos , Biomarcadores Tumorais , Doenças do Cão/metabolismo , Cães , Regulação Neoplásica da Expressão Gênica/fisiologia , Hemangiossarcoma/classificação , Proteínas de Homeodomínio/genética , Proteínas Supressoras de Tumor/genética , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/metabolismo , Proteínas de Transporte Vesicular/genéticaRESUMO
This study evaluated molecular characteristics that are potentially prognostic in cats with oral squamous cell carcinoma (SCC) that underwent stereotactic radiation therapy (SRT). Survival time (ST) and progression-free interval (PFI) were correlated with mitotic index, histopathological grades, Ki67 and epidermal growth factor receptor expressions, tumour microvascular density (MVD), and tumour oxygen tension (pO(2)). Median ST and PFI were 106 and 87 days, respectively (n = 20). Overall response rate was 38.5% with rapid improvement of clinical symptoms in many cases. Patients with higher MVD or more keratinized SCC had significantly shorter ST or PFI than patients with lower MVD or less keratinized SCC (P = 0.041 and 0.049, respectively). Females had significantly longer PFI and ST than males (P ≤ 0.016). Acute toxicities were minimal. However, treatment-related complications such as fractured mandible impacted quality of life. In conclusion, SRT alone should be considered as a palliative treatment. MVD and degree of keratinization may be useful prognostic markers.
Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças do Gato/radioterapia , Neoplasias Bucais/veterinária , Técnicas Estereotáxicas/veterinária , Animais , Carcinoma de Células Escamosas/radioterapia , Gatos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Neoplasias Bucais/radioterapia , Consumo de Oxigênio , Prognóstico , Análise de SobrevidaRESUMO
Feline oral squamous cell carcinoma (SCC) has very poor prognosis. Here, a retrospective pilot study was conducted on 20 feline oral SCC patients who underwent stereotactic radiation therapy (SRT), to evaluate: (1) the value of putative tumour initiating cell (TIC) markers of human head and neck SCC (CD44, Bmi-1); (2) telomere length (TL) specifically in putative TICs; and (3) tumour relative telomerase activity (TA). Significant inverse correlations were found between treatment outcomes and Bmi-1 expression, supporting the predictive value of Bmi-1 as a negative prognostic indicator. While TL exhibited a wide range of variability, particularly in very short fractions, many tumours possessed high levels of TA, which correlated with high levels of Bmi-1, Ki67 and EGFR. Taken together, our results imply that Bmi-1 and telomerase may represent novel therapeutic targets in feline oral SCC, as their inhibition - in combination with SRT - would be expected to have beneficial treatment outcome.
Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças do Gato/patologia , Neoplasias Bucais/veterinária , Células-Tronco Neoplásicas/patologia , Telomerase/metabolismo , Animais , Biomarcadores Tumorais , Carcinoma de Células Escamosas/patologia , Doenças do Gato/terapia , Gatos , Feminino , Masculino , Neoplasias Bucais/patologia , Valor Preditivo dos Testes , TelômeroRESUMO
The topic of pharmacology in space, i.e. the administration of drugs during space flight and the subsequent pharmacokinetic handling of the pharmaceuticals, is a new field about which little is known. In a two-part series, Claire Lathers and colleagues highlight some of the current questions in this field. In this first article the physiological and biochemical changes associated with weightlessness in space are discussed. These changes induce adaptive alterations which may influence the pharmacokinetic properties of drugs. The cardiovascular system is of particular relevance here. Also discussed are the classes of pharmacological agent that are most likely to be used during space flight for medical problems and thus, by necessity, will become drugs to be examined in space to determine whether their pharmacokinetic and pharmacodynamic properties are altered. Therapy of the most common spaceflight ailment-motion sickness-will be considered next month in Part 2.
Assuntos
Farmacocinética , Voo Espacial , Humanos , Ausência de PesoRESUMO
In this second article in the two-part series on pharmacology in space, Claire Lathers and colleagues discuss the pharmacology of drugs used to control motion sickness in space and note that the pharmacology of the 'ideal' agent has yet to be worked out. That motion sickness may impair the pharmacological action of a drug by interfering with its absorption and distribution because of alteration of physiology is a problem unique to pharmacology in space. The authors comment on the problem of designing suitable ground-based studies to evaluate the pharmacological effect of drugs to be used in space and discuss the use of salivary samples collected during space flight to allow pharmacokinetic evaluations necessary for non-invasive clinical drug monitoring.
Assuntos
Enjoo devido ao Movimento/tratamento farmacológico , Voo Espacial , HumanosRESUMO
This study represents the first systematic evaluation of dysrhythmias before, during, and after spaceflight including extravehicular activity (EVA). The data, based on 7 Shuttle crew members, revealed a nonsignificant decrease in ventricular and supraventricular ectopy during EVA, suggesting that the incidence of dysrhythmias is no greater during EVA than with any other phase of a mission or preflight.
Assuntos
Arritmias Cardíacas/fisiopatologia , Voo Espacial , Adulto , Eletrocardiografia Ambulatorial , Feminino , Humanos , Incidência , Masculino , Índice de Gravidade de Doença , Astronave , Ausência de PesoRESUMO
The effects of space flight on the cardiovascular system have been studied since the first manned flights. In several instances, the results from these investigations have directly contradicted the predictions based on established models. Results suggest associations between space flight's effects on other organ systems and those on the cardiovascular system. Such findings provide new insights into normal human physiology. They must also be considered when planning for the safety and efficiency of space flight crewmembers.
Assuntos
Fenômenos Fisiológicos Cardiovasculares , Voo Espacial , Adaptação Fisiológica , Humanos , Enjoo devido ao Movimento/etiologia , Ausência de Peso/efeitos adversosRESUMO
The effects of endurance training on vascular responsiveness to an alpha 1-agonist and the associated changes in baroreflex modulation of heart rate and vascular resistance were studied. Graded dosages of phenylephrine were given to eight treadmill-trained dogs and to eight untrained dogs; both groups were chronically instrumented and were sedated and resting when tested. These dosages were repeated after ganglionic blockade. Aortic pressure, cardiac output, central venous pressure, peripheral resistance, and heart rate were each averaged over 30 s before injection and 90 s after injection. The slope of the peripheral resistance-dose relationship was significantly increased in trained compared with untrained dogs in both the unblocked and blocked cases [unblocked: trained 0.89, untrained 0.47; blocked: trained 4.30, untrained 2.05 (mmHg.l-1.min)/(microgram.kg-1)]. The unblocked resistance slopes were reduced with respect to the blocked slopes by 77 (untrained) and 79% (trained). The slope of the heart rate-aortic pressure response was reduced, but not significantly, by endurance training. We conclude that 6 wk of endurance training in dogs resulted in a doubling of the vascular responsiveness to an alpha 1-agonist, with no significant change in the baroreflex regulation of resistance or heart rate.
Assuntos
Frequência Cardíaca/efeitos dos fármacos , Fenilefrina/farmacologia , Condicionamento Físico Animal , Pressorreceptores/fisiologia , Resistência Vascular/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Pressão Venosa Central/efeitos dos fármacos , Cães , Hemodinâmica , Masculino , Músculo Liso Vascular/fisiologia , Fenilefrina/administração & dosagem , DescansoRESUMO
Spaceflight is associated with decreased orthostatic tolerance after landing. Short-duration spaceflight (4-5 days) impairs one neural mechanism: the carotid baroreceptor-cardiac reflex. To understand the effects of longer-duration spaceflight on baroreflex function, we measured R-R interval power spectra, antecubital vein plasma catecholamine levels, carotid baroreceptor-cardiac reflex responses, responses to Valsalva maneuvers, and orthostatic tolerance in 16 astronauts before and after shuttle missions lasting 8-14 days. We found the following changes between preflight and landing day: 1) orthostatic tolerance decreased; 2) R-R interval spectral power in the 0.05 to 0.15-Hz band increased; 3) plasma norepinephrine and epinephrine levels increased; 4) the slope, range, and operational point of the carotid baroreceptor cardiac reflex response decreased; and 5) blood pressure and heart rate responses to Valsalva maneuvers were altered. Autonomic changes persisted for several days after landing. These results provide further evidence of functionally relevant reductions in parasympathetic and increases in sympathetic influences on arterial pressure control after spaceflight.
Assuntos
Sistema Nervoso Autônomo/fisiologia , Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Voo Espacial , Adulto , Astronautas , Eletrocardiografia , Epinefrina/sangue , Feminino , Frequência Cardíaca , Humanos , Hipotensão Ortostática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Pressorreceptores/fisiologia , Respiração/fisiologia , Sistema Nervoso Simpático/fisiologia , Manobra de Valsalva/fisiologiaRESUMO
Orthostatic intolerance is a predictable but poorly understood consequence of space travel. Because arterial baroreceptors modulate abrupt pressure transients, we tested the hypothesis that spaceflight impairs baroreflex mechanisms. We studied vagally mediated carotid baroreceptor-cardiac reflex responses (provoked by neck pressure changes) in the supine position and heart rate and blood pressure in the supine and standing positions in 16 astronauts before and after 4- to 5-day Space Shuttle missions. On landing day, resting R-R intervals and standard deviations, and the slope, range, and position of operational points on the carotid transmural pressure-sinus node response relation were all reduced relative to preflight. Stand tests on landing day revealed two separate groups (one maintained standing arterial pressure better) that were separated by preflight slopes, operational points, and supine and standing R-R intervals and by preflight-to-postflight changes in standing pressures, body weights, and operational points. Our results suggest that short-duration spaceflight leads to significant reductions in vagal control of the sinus node that may contribute to, but do not account completely for, orthostatic intolerance.
Assuntos
Artérias Carótidas/fisiologia , Coração/fisiologia , Pressorreceptores/fisiologia , Reflexo/fisiologia , Voo Espacial , Adulto , Pressão Sanguínea/fisiologia , Eletrocardiografia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Vago/fisiologiaRESUMO
Spaceflight causes adaptive changes in cardiovascular physiology, such as postflight orthostatic intolerance, that can have deleterious effects on astronauts. In-flight cardiovascular data are difficult to obtain, and results have been inconsistent. To determine normative in-flight changes in Shuttle astronauts, we measured heart rate, arterial pressure, and cardiac rhythm disturbances for 24-h periods before, during, and after spaceflight on Shuttle astronauts performing their normal routines. We found that heart rate, diastolic pressure, variability of heart rate and diastolic pressure, and premature ventricular contractions all were significantly reduced in flight. Systolic pressure and premature atrial contractions also tended to be reduced in flight. These data constitute the first systematic evaluation of in-flight changes in basic cardiovascular variables in Shuttle astronauts and suggest that a microgravity environment itself does not present a chronic stress to the cardiovascular system.