RESUMEN
Acute pulmonary embolism (PE) is a life-threatening disease, and several vasoconstrictors, including endothelin-1 (ET-1), play a key role in vasoconstriction and hypoxemia during the development of PE. Rho kinase is activated by various vasoconstrictors resulting in vascular contraction and remodeling. Recent evidence has revealed an important role of Rho kinase in the pathogenesis of systemic and pulmonary vascular diseases. However, contribution of Rho kinase in PE remains unclear. We thus investigated the role of Rho kinase in the PE rat model induced by intrajugular administration of polystyrene microspheres (mean diameter, 26 microm). At 6 h following the administration of microspheres (1.5 ml/kg), right ventricular systolic pressure (RVSP) was higher in the PE than in the control rats (15.8 +/- 1.6 vs. 32.9 +/- 7.5 mmHg). Arterial oxygen tension was lower (92.3 +/- 12.5 vs. 66.0 +/- 17.7 Torr), and alveolar-arterial difference in oxygen partial pressure was higher (3.9 +/- 3.8 vs. 36.5 +/- 26.9 Torr) in the PE rats. Western blotting analysis revealed upregulation and downregulation in expression of vascular cell adhesion molecule-1 and endothelial nitric oxide synthase in lungs from the PE rats, respectively, and radioimmunoassay demonstrated an increase in plasma ET-1 levels. Lung Rho kinase alpha expression was greater in the PE rats. At 5 h following administration of microspheres (0.75 ml/kg), intravenous Rho kinase inhibitors HA1077 and Y27632 (3 mg/kg each) attenuated elevation of RVSP (22.0 +/- 3.7, 17.1 +/- 3.2, 14.3 +/- 2.6 mmHg, PE, PE+HA1077, PE+Y27632) and the severity of hypoxemia (66.3 +/- 16.2, 94.9 +/- 23.0, 89.1 +/- 8.5 Torr, PE, PE+HA1077, PE+Y27632) in the PE rats. These results suggest that pulmonary endothelial dysfunction and activation of Rho kinase may contribute to the potentiation of vasoconstriction and hypoxemia in the PE rats.
Asunto(s)
Microesferas , Embolia Pulmonar/enzimología , Embolia Pulmonar/etiología , Quinasas Asociadas a rho/metabolismo , Enfermedad Aguda , Animales , Análisis de los Gases de la Sangre , Presión Sanguínea/efectos de los fármacos , Endotelina-1/sangre , Hemodinámica/efectos de los fármacos , Inyecciones Intravenosas , Pulmón/efectos de los fármacos , Pulmón/enzimología , Pulmón/patología , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , Poliestirenos , Inhibidores de Proteínas Quinasas/farmacología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/patología , Embolia Pulmonar/sangre , Embolia Pulmonar/inducido químicamente , Ratas , Ratas Sprague-Dawley , Molécula 1 de Adhesión Celular Vascular/metabolismo , Quinasas Asociadas a rho/antagonistas & inhibidoresRESUMEN
We report the case of a 42-year-old woman with Klippel-Feil syndrome, who showed severe hypermobility of the upper cervical spine without neurological involvement for more than 40 years. Radiographs revealed the presence of the odontoid bone and fusion of the atlas, odontoid bone, and occiput. Congenital fusion was present from the axis to C5 as a block vertebra. Lateral flexion-extension radiographs revealed severe hypermobility at the junction between the odontoid bone and the axis. Prophylactic surgical stabilization has been recommended in patients with severe hypermobility, but adjacent disc problems may possibly occur at the unfused levels in the future. We believe that early prophylactic stabilization should not be indicated for Klippel-Feil syndrome without neurological involvement only because of hypermobility.