The Effects of Acute and Chronic Inflammation on the Dynamics of Fluid Shift of Ringer's Solution and Hemodynamics during Surgery.

The aim of this study was to investigate the influences of acute and chronic inflammation on the dynamics of fluid shift of Ringer's solution and hemodynamics in patients during surgery. Thirty-seven patients with the American Society of Anesthesiologists (ASA) grades I-II were enrolled and allocated to two study groups according to the type of disease and operation and inflammation, including patients undergoing emergency appendectomy (Acute group, n = 19) and patients undergoing elective cholecystectomy (Chronic group, n = 18). All of the patients were administered 15 mL/kg of Ringer's lactated (LR) solution at a constant rate over 35 min before the induction of anesthesia. Plasma dilution (PD), volume expansion (VE), volume expansion efficiency (VEE), and extravascular volume (EVV) were calculated based on the concentration of hemoglobin within 2 h post-infusion. Heart rate (HR), arterial blood pressure and urine output were also recorded. PD and VE peaked at the end of infusion, while VEE peaked at the beginning of infusion in all of the patients. After infusion, PD, VE and VEE in the Acute group were all higher than those in the Chronic group (p < 0.05). PD and VE were higher during anesthesia or surgery than during awake or non-surgery (p < 0.001). The mean arterial pressure (MAP) and diastolic pressure (DBP) in the Acute group were significantly lower (p < 0.001) and HR was significantly higher (p < 0.001) than in the Chronic group during the study periods. It was suggested that patients with acute inflammation be treated with individualized fluid therapy during surgery.

Electrocardiogram and heart rate variability assessment in patients with common autoimmune diseases: a methodological review.

The aim of this article was to summarize current knowledge about the potential clinical utility of electrocardiogram (ECG) and heart rate variability (HRV) measures in patients with 4 common autoimmune diseases (ADs): rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behcet's disease (BD), and systemic sclerosis (SSc). A search was conducted of the PubMed, Embase, and Scopus databases using terms and a controlled vocabulary associated with these ADs, ECG, and HRV. The available, full-text articles published in English were considered. In all, 20 publications that examined the direct effect of these diseases on the heart were selected according to a systematic review protocol. Time-frequency domain analysis revealed that HRV parameters were lower in patients with the selected ADs in comparison with control groups. An increased QT dispersion and heart rate corrected QT, which are well-known as risk factors for sudden cardiac death, were observed in the patient group. In some studies, a correlation was seen between the duration of the disease and its activity, while others did not report such an association. Heart rate turbulence parameters were also examined. Turbulence onset was increased in SLE and SSc patients, while the turbulence slope was decreased in SLE patients. There was no significant change in these parameters in BD patients. Patients with ADs demonstrate abnormal HRV and ECG parameters, which indicates an autonomic cardiac functional impairment. Measurement of these parameters can be a useful clinical tool in the diagnosis and prediction of some disorders in patients with ADs. Both of these signals can provide helpful information for physicians to trace the efficacy of prescribed medicines.

Early Identification of Acute Lung Injury in a Porcine Model of Hemorrhagic Shock.

BACKGROUND: Acute lung injury (ALI) is a frequent complication after severe trauma. Lung-protective ventilation strategies and damage control resuscitation have been proposed for the prevention of ALI; however, there are no clinical or laboratory parameters to predict who is at risk of developing ALI after trauma. In the present study, we explored pulmonary inflammatory markers as a potential predictor of ALI using a porcine model of hemorrhagic shock. MATERIALS AND METHODS: Female swine were randomized to mechanical ventilation with low tidal volume (VT) (6 mL/kg) or high VT (12 mL/kg). After equilibration, animals underwent pressure-controlled hemorrhage (mean arterial pressure [MAP] 35 ± 5 mmHg) for 1 h, followed by resuscitation with fresh whole blood or Hextend. They were maintained at MAP of 50 ± 5 mmHg for 3 h in the postresuscitation phase. Bronchoalveolar lavage fluids were collected hourly and analyzed for inflammatory markers. Lung samples were taken, and porcine neutrophil antibody staining was used to evaluate the presence of neutrophils. ELISA evaluated serum porcine surfactant protein D levels. Sham animals were used as negative controls. RESULTS: Pigs that underwent hemorrhagic shock had higher heart rates, lower cardiac output, lower MAPs, and worse acidosis compared with sham at the early time points (P < 0.05 each). There were no significant differences in central venous pressure or pulmonary capillary wedge pressure between groups. Pulmonary neutrophil infiltration, as defined by neutrophil antibody staining on lung samples, was greater in the shock groups regardless of resuscitation fluid (P < 0.05 each). Bronchoalveolar lavage fluid neutrophil levels were not different between groups. There were no differences in levels of porcine surfactant protein D between groups at any time points, and the levels did not change over time in each respective group. CONCLUSIONS: Our study demonstrates the reproducibility of a porcine model of hemorrhagic shock that is consistent with physiologic changes in humans in hemorrhagic shock. Pulmonary neutrophil infiltration may serve as an early marker for ALI; however, the practicality of this finding has yet to be determined.

Long-term cardiovascular autonomic and clinical changes after immunoglobulin G immunoadsorption therapy in autoimmune autonomic ganglionopathy.

: A 63-year-old male was diagnosed with autoimmune autonomic ganglionopathy based on the finding of plasma antibodies to the nicotinic acetylcholine receptor (nAChR) of autonomic ganglia. He complained of mouth and eye dryness, dysphagia, severe constipation, erectile dysfunction, urgency, frequent urination, habitual orthostatic syncope and presyncope. A remarkable symptomatic orthostatic hypotension without changes in heart rate was present. We here describe the 3-year time course of the changes in spectral indices of cardiovascular autonomic control LF/HF and LFSAP, dysautonomia symptoms intensity and anti-nAChR antibodies following repetitive selective immunoadsorptions. During the follow-up, the reduction of anti-nAChR antibodies produced by immunoadsorption was associated with a diminished orthostatic hypotension, a restored capability to increase LF/HF, LFSAP and norepinephrine in upright position, a decline in the intensity of autonomic symptoms and an improvement of life quality. Spectral parameters LF/HF and LFSAP may represent noninvasive, low-cost biomarkers suitable for autoimmune autonomic ganglionopathy patients' clinical follow-up.

Cholinergic Pathway Suppresses Pulmonary Innate Immunity Facilitating Pneumonia After Stroke.

BACKGROUND AND PURPOSE: Temporary immunosuppression has been identified as a major risk factor for the development of pneumonia after acute central nervous system injury. Although overactivation of the sympathetic nervous system was previously shown to mediate suppression of systemic cellular immune responses after stroke, the role of the parasympathetic cholinergic anti-inflammatory pathway in the antibacterial defense in lung remains largely elusive. METHODS: The middle cerebral artery occlusion model in mice was used to examine the influence of the parasympathetic nervous system on poststroke immunosuppression. We used heart rate variability measurement by telemetry, vagotomy, α7 nicotinic acetylcholine receptor-deficient mice, and parasympathomimetics (nicotine, PNU282987) to measure and modulate parasympathetic activity. RESULTS: Here, we demonstrate a rapidly increased parasympathetic activity in mice after experimental stroke. Inhibition of cholinergic signaling by either vagotomy or by using α7 nicotinic acetylcholine receptor-deficient mice reversed pulmonary immune hyporesponsiveness and prevented pneumonia after stroke. In vivo and ex vivo studies on the role of α7 nicotinic acetylcholine receptor on different lung cells using bone marrow chimeric mice and isolated primary cells indicated that not only macrophages but also alveolar epithelial cells are a major cellular target of cholinergic anti-inflammatory signaling in the lung. CONCLUSIONS: Thus, cholinergic pathways play a pivotal role in the development of pulmonary infections after acute central nervous system injury.

Progenitor cells are mobilized by acute psychological stress but not beta-adrenergic receptor agonist infusion.

OBJECTIVES: Stimuli that activate the sympathetic nervous system, such as acute psychological stress, rapidly invoke a robust mobilization of lymphocytes into the circulation. Experimental animal studies suggest that bone marrow-derived progenitor cells (PCs) also mobilize in response to sympathetic stimulation. Here we tested the effects of acute psychological stress and brief pharmacological ß-adrenergic (ßAR) stimulation on peripheral PC numbers in humans. METHODS: In two studies, we investigated PC mobilization in response to an acute speech task (n=26) and ßAR-agonist (isoproterenol) infusion (n=20). A subset of 8 participants also underwent the infusion protocol with concomitant administration of the ßAR-antagonist propranolol. Flow cytometry was used to enumerate lymphocyte subsets, total progenitor cells, total haematopoietic stem cells (HSC), early HSC (multi-lineage potential), late HSC (lineage committed), and endothelial PCs (EPCs). RESULTS: Both psychological stress and ßAR-agonist infusion caused the expected mobilization of total monocytes and lymphocytes and CD8(+) T lymphocytes. Psychological stress also induced a modest, but significant, increase in total PCs, HSCs, and EPC numbers in peripheral blood. However, infusion of a ßAR-agonist did not result in a significant change in circulating PCs. CONCLUSION: PCs are rapidly mobilized by psychological stress via mechanisms independent of ßAR-stimulation, although the findings do not exclude ßAR-stimulation as a possible cofactor. Considering the clinical and physiological relevance, further research into the mechanisms involved in stress-induced PC mobilization seems warranted.

Differential effects of complement activation products c3a and c5a on cardiovascular function in hypertensive pregnant rats.

Early-onset pre-eclampsia is characterized by decreased placental perfusion, new-onset hypertension, angiogenic imbalance, and endothelial dysfunction associated with excessive activation of the innate immune complement system. Although our previous studies demonstrated that inhibition of complement activation attenuates placental ischemia-induced hypertension using the rat reduced uterine perfusion pressure (RUPP) model, the important product(s) of complement activation has yet to be identified. We hypothesized that antagonism of receptors for complement activation products C3a and C5a would improve vascular function and attenuate RUPP hypertension. On gestational day (GD) 14, rats underwent sham surgery or vascular clip placement on ovarian arteries and abdominal aorta (RUPP). Rats were treated once daily with the C5a receptor antagonist (C5aRA), PMX51 (acetyl-F-[Orn-P-(D-Cha)-WR]), the C3a receptor antagonist (C3aRA), SB290157 (N(2)-[(2,2-diphenylethoxy)acetyl]-l-arginine), or vehicle from GD 14-18. Both the C3aRA and C5aRA attenuated placental ischemia-induced hypertension without affecting the decreased fetal weight or decreased concentration of free circulating vascular endothelial growth factor (VEGF) also present in this model. The C5aRA, but not the C3aRA, attenuated placental ischemia-induced increase in heart rate and impaired endothelial-dependent relaxation. The C3aRA abrogated the acute pressor response to C3a peptide injection, but it also unexpectedly attenuated the placental ischemia-induced increase in C3a, suggesting nonreceptor-mediated effects. Overall, these results indicate that both C3a and C5a are important products of complement activation that mediate the hypertension regardless of the reduction in free plasma VEGF. The mechanism by which C3a contributes to placental ischemia-induced hypertension appears to be distinct from that of C5a, and management of pregnancy-induced hypertension is likely to require a broad anti-inflammatory approach.

Vaccine-induced inflammation attenuates the vascular responses to mental stress.

Inflammation is associated with poorer vascular function, with evidence to suggest that inflammation can also impair the vascular responses to mental stress. This study examined the effects of vaccine-induced inflammation on vascular responses to mental stress in healthy participants. Eighteen male participants completed two stress sessions: an inflammation condition having received a typhoid vaccination and a control (non-inflamed) condition. Tumor necrosis factor-alpha and interleukin-6 (p's<.001) increased following vaccination, confirming modest increases in inflammation. Mental stress increased blood flow, blood pressure, heart rate, and cardiac output in both conditions (all p's<.001), but the blood flow response to stress was attenuated having received the vaccination compared to the control condition (p's<.05). These results further implicate the interaction between inflammation and the vasculature as a mechanism through which stress may trigger myocardial infarction.

Protective effect of aquacultured flounder fish-derived peptide against oxidative stress in zebrafish.

This study investigates the protective effect of aquacultured flounder fish-derived peptide (AFFP) against 2,2-azobis-(2-amidinopropane) hydrochloride (AAPH)-induced oxidative damage in a zebrafish model. Zebrafish embryos were evaluated for the protective effect by heartbeat rate, survival rate, ROS generation, lipid peroxidation, and cell death. In the results, the AAPH group showed a low survival rate, whereas the AFFP and AAPH co-treated group increased a survival rate. Also, AFFP dose-dependently reduced AAPH-induced intracellular ROS and lipid peroxidation, and decreased cell death in AAPH-induced zebrafish. These results revealed that AFFP could be used as a natural antioxidant, and that the zebrafish provides an alternative in vivo model to efficiently evaluate the antioxidative effects of peptides on fishes.

Combined inhibition of complement C5 and CD14 markedly attenuates inflammation, thrombogenicity, and hemodynamic changes in porcine sepsis.

Complement and the TLR family constitute two important branches of innate immunity. We previously showed attenuating effects on inflammation and thromogenicity by inhibiting the TLR coreceptor CD14 in porcine sepsis. In the present study, we explored the effect of the C5 and leukotriene B4 inhibitor Ornithodoros moubata complement inhibitor (OmCI; also known as coversin) alone and combined with anti-CD14 on the early inflammatory, hemostatic, and hemodynamic responses in porcine Escherichia coli-induced sepsis. Pigs were randomly allocated to negative controls (n = 6), positive controls (n = 8), intervention with OmCI (n = 8), or with OmCI and anti-CD14 (n = 8). OmCI ablated C5 activation and formation of the terminal complement complex and significantly decreased leukotriene B4 levels in septic pigs. Granulocyte tissue factor expression, formation of thrombin-antithrombin complexes (p < 0.001), and formation of TNF-α and IL-6 (p < 0.05) were efficiently inhibited by OmCI alone and abolished or strongly attenuated by the combination of OmCI and anti-CD14 (p < 0.001 for all). Additionally, the combined therapy attenuated the formation of plasminogen activator inhibitor-1 (p < 0.05), IL-1ß, and IL-8, increased the formation of IL-10, and abolished the expression of wCD11R3 (CD11b) and the fall in neutrophil cell count (p < 0.001 for all). Finally, OmCI combined with anti-CD14 delayed increases in heart rate by 60 min (p < 0.05) and mean pulmonary artery pressure by 30 min (p < 0.01). Ex vivo studies confirmed the additional effect of combining anti-CD14 with OmCI. In conclusion, upstream inhibition of the key innate immunity molecules, C5 and CD14, is a potential broad-acting treatment regimen in sepsis as it efficiently attenuated inflammation and thrombogenicity and delayed hemodynamic changes.

Vagal nerve activity as a moderator of brain-immune relationships.

We investigated whether vagal tone, as assessed by heart rate variability (HRV), moderates the neural correlates of immune and physiological responses to acute stress. Participants with low and high baseline HRV underwent a reversal learning task as an acute stressor. Natural killer cells, norepinephrine, and adrenocorticotropic hormone in peripheral blood changed with acute stress in the high HRV group only. Activity in the prefrontal cortex and striatum correlated with the immune and physiological indices in the high HRV group. High vagal tone may reflect more flexible top-down brain regulation of immune and physiological activity.

Avaliação da variabilidade da frequência cardíaca de idosos diabéticos e não diabéticos / Assessment of heart rate variability in elderly diabetic and nondiabetic patients

INTRODUÇÃO: O cenário de envelhecimento populacional e o aumento das Doenças Crônicas Não Transmissíveis (DCNT) requer o desenvolvimento e validação de métodos diagnóstico e de ferramentas não invasivas para identificação de fatores de risco e estadiamento destas doenças. Entre estes métodos evidencia-se a análise da modulação autonômica do coração por meio da Variabilidade da Frequência Cardíaca (VFC). OBJETIVO: Analisar a variabilidade da frequência cardíaca de idosos diabéticos (DM+) e não diabéticos (DM–) residentes em um município baiano; avaliar a resposta da variabilidade da frequência cardíaca na realização da manobra de levantar-se rapidamente. MÉTODOS: estudo epidemiológico transversal, de abordagem censitária. Desenvolvido com 205 idosos da zona urbana do munícipio de Aiquara-BA, após aplicação os critérios de inclusão e exclusão. Os dados da VFC foram coletados através do monitor Polar RS800CX...

INTRODUCTION: The scenario of population aging and the increase of Chronic Noncommunicable Diseases (NCDs) requires the development and validation of diagnostic methods and non-invasive tools for identification of risk factors and staging of these diseases.Among these methods, the analysis of autonomic modulation of the heart using the Heart Rate Variability (HRV) becomes evident. OBJECTIVE: To analyze the heart rate variability in diabetic (DM+) and nondiabetic (DM–) elderlies residents in a municipality of Bahia, and also to know the response of heart rate variability in performance of the quickly stand up maneuver. METHODS: cross-sectional study of censitary approach. Carried out with 205 elderlies in the urban area of the municipality of Aiquara-BA, after had applied the inclusion and exclusion criteria. HRV data were collected through the Polar RS800CX...

Effects of a "two-hit" model of organ damage on the systemic inflammatory response and development of laminitis in horses.

The role of endotoxemia in the development of laminitis remains unclear. Although systemic inflammation is a risk factor for laminitis in hospitalized horses, experimental endotoxin administration fails to induce the disease. While not sufficient to cause laminitis by itself, endotoxemia might predispose laminar tissue to damage from other mediators during systemic inflammation. In "two-hit" models of organ damage, sequential exposure to inflammatory stimuli primes the immune system and causes exaggerated inflammatory responses during sepsis. Acute laminitis shares many characteristics with sepsis-associated organ failure, therefore an equine "two-hit" sepsis model was employed to test the hypothesis that laminitis develops with increased frequency and severity when repeated inflammatory events exacerbate systemic inflammation and organ damage. Twenty-four light breed mares (10) and geldings (14) with chronic disease conditions or behavioral abnormalities unrelated to laminitis that warranted euthanasia were obtained for the study. Horses were randomly assigned to receive an 8-h intravenous infusion of either lipopolysaccharide (5 ng/kg/h) or saline beginning at -24h, followed by oligofructose (OF; 5 g/kg) via nasogastric tube at 0 h. Euthanasia and tissue collection occurred at Obel grade 2 laminitis, or at 48 h if laminitis had not developed. Liver biopsies were performed at 24h in laminitis non-responders. Blood cytokine gene expression was measured throughout the study period. Lipopolysaccharide and OF administration independently increased mean rectal temperature (P<0.001), heart rate (P=0.003), respiratory rate (P<0.001), and blood interleukin (IL)-1ß gene expression (P<0.0016), but responses to OF were not exaggerated in endotoxin-pretreated horses. The laminitis induction rate did not differ between treatment groups and was 63% overall. When horses were classified as laminitis responders and non-responders, area under the blood IL-1ß expression curve (P=0.010) and liver and lung gene expression of IL-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor-α (P<0.05) were higher in responders following OF administration. The results indicate that endotoxin pretreatment did not enhance responses to OF. However, systemic inflammation was more pronounced in laminitis responders compared to non-responders, and tissue-generated inflammatory mediators could pose a greater risk than those produced by circulating leukocytes.

Cytokine profile of the blood in mice with normal and abnormal heart rhythm.

Differences in the pools of 10 cytokine were found in blood samples from the caudal vein of mice with normal and abnormal heart rhythm. Both groups were albino mice bred by us and differing from mdx albino mice by the absence of mutation in muscular dystrophin gene. Mice with normal heart rhythm had low IL-17 content and elevated concentrations of proinflammatory cytokines IL-6 and IL-1α in comparison with the normal (according to published data). In mice with bradyarrhythmias, increased blood levels of IL-10, IL-6, IL-5, IL-2, IL-1α, IL-17, IL-4, TNF-α, and granulocyte-macrophage colony-stimulating factor were detected. The relative content of IL-4 and IL-17 in the total cytokine pool increased. The lifespan of mice with bradyarrhythmias and cytokine hyperexpression was shorter by 2-3 months in comparison with mice without heart rhythm disturbances and moderate changes in the cytokine pool.

Valoración de la Frecuencia Cardíaca de Recuperación después de un programa de entrenamiento de fuerza-resistencia en hipoxia / Changes in heart rate recovery index after a programme of strength/endurance training in hypoxia

Objetivo: Doce sujetos jóvenes físicamente activos se dividieron en dos grupos equilibrados para entrenar en hipoxia (HYP) y normoxia (NOR). Material y métodos: Los sujetos fueron asignados a cada grupo en base a los resultados en una prueba previa de salto en contramovimiento de sesenta segundos (CMJ60). Ambos grupos realizaron durante 4 semanas un entrenamiento idéntico de fuerza (volumen, intensidad, carácter y condiciones de esfuerzo) en las extremidades inferiores (squat, half-squat y saltos). Resultados: Ambos grupos mejoraron en todos los casos. Se analizó la evolución temporal de la frecuencia cardiaca durante la prueba CMJ60 y el posterior período de recuperación de tres minutos. El grupo HYP (n=5) refleja una mejoría del índice de recuperación de la frecuencia cardiaca en comparación con el grupo NOR (prueba t de Student) después de 2 (p=0,03) y 3 (p=0,05) minutos de finalizar el test de saltos. Conclusiones: Concluimos que un protocolo de entrenamiento de fuerza resistencia (12 sesiones en 4 semanas) de las extremidades inferiores en altitud simulada podría mejorar el índice de recuperación de la frecuencia cardiaca en comparación con el mismo entrenamiento realizado a nivel del mar(AU)

Objective: To determine whether twelve sessions of resistance training on lower limbs at simulated altitude (2500m) were efficient to elicit an improvement in heart rate recovery index in the first 3min of recovery after a maximal jump test. Materials and methods: Twelve young physically active subjects were divided in two balanced groups for training in hypoxia (HYP) and normal oxygen (NOR). The subjects were assigned to each group based on previous test results in the 60s counter-movement jump test (CMJ60). Results: Both groups performed identical strength training (volume, intensity, character and effort conditions) on the lower limbs (squats, half-squats and jumps) for 4 weeks. Both groups improved the measured parameters in all cases. We analyzed the time course of heart rate during the CMJ60 test and the subsequent 3min recovery period. HYP group (n=5) improved the heart rate recovery index as compared to NOR group (Student's t-test) at minute 2 (P=0.03) and minute 3 (P=0.05). Conclusions: We conclude that a protocol of resistance training on lower limbs (12 sessions in 4 weeks) at a simulated altitude could improve heart rate recovery index compared to the same training performed at sea level(AU)

Behavioural modification of the cholinergic anti-inflammatory response to C-reactive protein in patients with hypertension.

OBJECTIVES: A central hypothesis of the cholinergic anti-inflammatory reflex model is that innate immune activity is inhibited by the efferent vagus. We evaluated whether changes in markers of tonic or reflex vagal heart rate modulation following behavioural intervention were associated inversely with changes in high-sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6). DESIGN: Subjects diagnosed with hypertension (n = 45, age 35-64 years, 53% women) were randomized to an 8-week protocol of behavioural neurocardiac training (with heart rate variability biofeedback) or autogenic relaxation. Assessments before and after intervention included pro-inflammatory factors (hsCRP, IL-6), markers of vagal heart rate modulation [RR high-frequency (HF) power within 0.15-0.40 Hz, baroreflex sensitivity and RR interval], conventional measures of lipoprotein cholesterol and 24-h ambulatory systolic and diastolic blood pressure. RESULTS: Changes in hsCRP and IL-6 were not associated with changes in lipoprotein cholesterol or blood pressure. After adjusting for anti-inflammatory drugs and confounding factors, changes in hsCRP related inversely to changes in HF power (ß = -0.25±0.1, P = 0.02), baroreflex sensitivity (ß = -0.33±0.7, P = 0.04) and RR interval (ß = -0.001 ± 0.0004, P = 0.02). Statistically significant relationships were not observed for IL-6. CONCLUSIONS: Changes in hsCRP were consistent with the inhibitory effect of increased vagal efferent activity on pro-inflammatory factors predicted by the cholinergic anti-inflammatory reflex model. Clinical trials for patients with cardiovascular dysfunction are warranted to assess whether behavioural interventions can contribute independently to the chronic regulation of inflammatory activity and to improved clinical outcomes.

Airway resistance, inflammation and oxidative stress following exposure to diesel exhaust particle in angiotensin II-induced hypertension in mice.

Exposure to particulate matter is a risk factor for respiratory and cardiovascular diseases. However, the mechanisms underlying these effects are not well understood. Here, we compared the impact of diesel exhaust particles (DEP) on airway resistance, inflammation and oxidative stress in normal mice, or mice made hypertensive by implanting osmotic minipump infusing angiotensin II. On day 13 after the onset of infusion, angiotensin II induced significant increase in heart rate (P<0.05) and systolic blood pressure (P<0.0001). On the same day, mice were intratracheally instilled with either DEP (15 µg/mouse) or saline. Twenty-four hour later, the measurement of airway reactivity to methacholine (0-10mg/ml) in vivo by a forced oscillation technique showed a significant and dose dependent increase in airway resistance in normotensive mice exposed to DEP compared to those exposed to saline. In hypertensive mice, there was no difference in airway resistance in DEP versus saline exposed mice. However, following exposure to DEP, airway resistance significantly increased in normotensive versus hypertensive mice. Bronchoalveolar lavage (BAL) fluid analysis showed a significant increase in macrophage numbers in normotensive mice exposed to DEP compared to those exposed to saline, and to hypertensive mice exposed to DEP. Neutrophil numbers were significantly increased in both normotensive and hypertensive mice exposed to DEP compared with their respective control groups. Superoxide dismutase activity was significantly decreased following DEP exposure in both normotensive and hypertensive mice compared to their respective controls. However, total proteins, a marker for increase of epithelial permeability, and malondialdehyde, a reflection of lipid peroxidation, were only increased in normotensive mice exposed to DEP. Therefore, our data suggest that DEP do not aggravate airway resistance and inflammation in angiotensin II-induced hypertensive mice. On the contrary, at the dose of DEP and time point investigated, airway resistance, inflammation and oxidative stress are increased in normotensive compared to hypertensive mice.

Role of anti-ß1 adrenergic antibodies from patients with periodontitis in cardiac dysfunction.

BACKGROUND: The presence of serum autoantibodies against ß(1) adrenoreceptors (ß(1)-ARs) in human gingival fibroblast from patients with periodontitis inhibits primary cell-specific growth and induces over-expression of pro-inflammatory mediators. Serum ß(1)-AR autoantibodies from patients with periodontitis react with myocardium and modify cardiac contractility. The relationship between the presence of serum ß(1)-AR autoantibodies and alterations in heart rate variability (HRV) was also studied. METHODS: An enzyme-linked immunosorbent assay (ELISA) using cardiac and gingival fibroblast membranes or synthetic peptides corresponding to the second extracellular loop of human ß(1)-AR was used to detect serum autoantibodies. The HRV was assessed from RR interval files generated from 22:00 to 08:00 hours. The autoantibody effects on contractility were measured on spontaneous rat isolated atria. RESULTS: Circulating autoantibodies from 36 patients with periodontitis and 20 healthy individuals (controls) interacted with fibroblasts, the cardiac surface, and ß(1)-AR synthetic peptides. The distributions of serum antibodies against gingival and myocardium membranes and ß(1)-AR synthetic peptide were 88.8%, 77.7%, and 92.8%, respectively. Moreover, 88.5% of patients with periodontitis whose sera were positive against ß(1)-AR synthetic peptide had decreased HRV. The corresponding affinity-purified anti-ß(1)-AR peptide IgG displayed partial agonist-like activity modifying the isolated atria contractility. CONCLUSION: This manuscript describes that patients with periodontitis showed increased levels of serum IgG with reactive activity against ß(1)-AR. Those patients demonstrated decrease in heart rate, and IgG derived from their sera induced aberrant contractility of heart atrium. We propose that periodontitis increases the risk of cardiovascular diseases, although it increases anti-ß(1)-AR autoantibody that alters myocardial contractility.

Aerosol exposure to the angola strain of marburg virus causes lethal viral hemorrhagic Fever in cynomolgus macaques.

Cynomolgus macaques were exposed to the Angola strain of Lake Victoria Marburg virus (MARV) by aerosol to examine disease course and lethality. Macaques became febrile 4 to 7 days postexposure; the peak febrile response was delayed 1 to 2 days in animals that received a lower dose; viremia coincided with the onset of fever. All 6 macaques succumbed to the infection, with the 3 macaques in the low-dose group becoming moribund on day 9, a day later than the macaques in the high-dose group. Gross pathologic lesions included maculopapular cutaneous rash; pulmonary congestion and edema; pericardial effusion; enlarged, congested, and/or hemorrhagic lymphoid tissues; enlarged friable fatty liver; and pyloric and duodenal congestion and/or hemorrhage. Fibrinous interstitial pneumonia was the most consistent pulmonary change. Lymphocytolysis and lymphoid depletion, as confirmed by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling), were observed in the mediastinal lymph nodes and spleen. MARV antigen was detected in the lungs, mediastinal lymph nodes, spleen, and liver of all animals examined. In infected macaques, nuclear expression of interleukin-33 was lost in pulmonary arteriolar and mediastinal lymph node high endothelial venule endothelial cells; interleukin-33-positive fibroblastic reticular cells in the mediastinal lymph node were consistently negative for MARV antigen. These macaques exhibited a number of features similar to those of human filovirus infections; as such, this model of aerosolized MARV-Angola might be useful in developing medical countermeasures under the Animal Rule.