RESUMO
OBJECTIVES: The pathogenesis of reactive arthritis (ReA), an aseptic synovitis that follows an extra-articular infection, is incompletely known. We studied the impact of tumour necrosis factor receptor (TNFR) p55 deficiency on the progression to ReA after oral Yersinia enterocolitica O:3 infection, the Yersinia antigens triggering articular inflammation and a possible articular TNFRp55-mediated mechanism that protects against ReA. METHODS: Wild-type C57BL/6 and TNFRp55-/- mice were orogastrically infected with Y. enterocolitica O:3 and monitored for survival and arthritis development. The bacterial load was determined in mesenteric lymph nodes (MLNs), the spleen and joints. Interferon (IFN)-gamma, TNF-alpha and IL-10 mRNA expression in MLN and joints were analysed by reverse transcription-polymerase chain reaction (RT-PCR). Articular antibodies to Yersinia antigens, TNF-alpha protein and nitric oxide (NO) levels were assessed. Acute arthritis was evaluated after joint injection of Yersinia antigens. RESULTS: The survival rate was 60% in TNFRp55-/- mice. They showed impaired bacterial clearance in MLN, the spleen and joints, and excessive mRNA expression of pro-inflammatory cytokines in MLN. Clinical and histological examinations revealed that TNFRp55-/- mice developed severe arthritis. Moreover, augmented articular outer membrane protein (OMP)-specific antibodies and TNF-alpha but impaired NO levels were detected in TNFRp55-/- mice. Synovial inflammatory response was detected by joint OMP injection. CONCLUSIONS: TNFRp55-mediated immune mechanisms prevent ReA development after oral infection with Y. enterocolitica O:3. Yersinia OMPs are the relevant antigens triggering ReA. NO induction through TNFRp55 signalling could have a local antibacterial function to prevent ReA. This study could contribute to ReA-specific therapeutic studies.
Assuntos
Antígenos de Bactérias/imunologia , Artrite Experimental/imunologia , Artrite Reativa/imunologia , Receptores Tipo I de Fatores de Necrose Tumoral/imunologia , Yersiniose/imunologia , Yersinia enterocolitica/imunologia , Animais , Anticorpos Antibacterianos/biossíntese , Artrite Experimental/microbiologia , Artrite Experimental/patologia , Artrite Reativa/microbiologia , Artrite Reativa/patologia , Suscetibilidade a Doenças , Articulações/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/biossíntese , Receptores Tipo I de Fatores de Necrose Tumoral/deficiência , Fator de Necrose Tumoral alfa/biossíntese , Yersiniose/patologiaRESUMO
PURPOSE: To study the hemodynamic effects of latissimus dorsi dynamic pulmonaroplasty in open chest animals. METHODS: Six anesthetized mongrel dogs were subjected to diastolic counterpulsation using electrically stimulated latissimus dorsi muscle flap wrapped around the aortic and pulmonary arteries roots and gated to the surface electrocardiogram. Aortic and Pulmonanary pressures as well as cardiac output and cardiac index were measured. RESULTS: Diastolic counterpulsation resulted in a significant increase in cardiac output (from 2.35 +/- 0.26 to 2.45 +/- 0.28 l/min) (p < 0.005) and cardiac index (from 0.108 +/- 0.020 to 0.113 +/- 0.020 l/min/kg) (p < 0.05). The diastolic pulmonary arterial efficiency index showed a significant increase when latissimus dorsi stimulation was on (from 8.37 +/- 0.60 to 11.65 +/- 0.83 mmHg); (p < 0.005). CONCLUSION: Latissimus dorsi dynamic pulmonaroplasty provides an effective means of arterial counter pulsation in open chest dogs.