RESUMEN
Gammaherpesviruses (γHV) are implicated in the pathogenesis of pulmonary fibrosis in humans and murine models of lung fibrosis, however there is little direct experimental evidence that such viruses induce lung fibrosis in the natural host. The equine γHV EHV 5 is associated with equine multinodular pulmonary fibrosis (EMPF), a progressive fibrosing lung disease in its natural host, the horse. Experimental reproduction of EMPF has not been attempted to date. We hypothesized that inoculation of EHV 5 isolated from cases of EMPF into the lungs of clinically normal horses would induce lung fibrosis similar to EMPF. Neutralizing antibody titers were measured in the horses before and after inoculation with EHV 5. PCR and virus isolation was used to detect EHV 5 in antemortem blood and BAL samples, and in tissues collected postmortem. Nodular pulmonary fibrosis and induction of myofibroblasts occurred in EHV 5 inoculated horses. Mean lung collagen in EHV 5 inoculated horses (80 µg/mg) was significantly increased compared to control horses (26 µg/mg) (p < 0.5), as was interstitial collagen (32.6% ± 1.2% vs 23% ± 1.4%) (mean ± SEM; p < 0.001). Virus was difficult to detect in infected horses throughout the experiment, although EHV 5 antigen was detected in the lung by immunohistochemistry. We conclude that the γHV EHV 5 can induce lung fibrosis in the horse, and hypothesize that induction of fibrosis occurs while the virus is latent within the lung. This is the first example of a γHV inducing lung fibrosis in the natural host.
Asunto(s)
Gammaherpesvirinae/patogenicidad , Enfermedades de los Caballos/virología , Fibrosis Pulmonar/virología , Animales , Anticuerpos Antivirales/inmunología , Gammaherpesvirinae/inmunología , Enfermedades de los Caballos/inmunología , Enfermedades de los Caballos/metabolismo , Caballos , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/metabolismoRESUMEN
OBJECTIVE: To use noninvasive respiratory inductance plethysmography (RIP) to investigate differences in breathing patterns between horses with and without recurrent airway obstruction (RAO) during the onset of airway obstruction induced through confinement to stables. ANIMALS: 12 horses with no history or clinical signs of respiratory disease (control horses) and 7 RAO-affected horses. PROCEDURES: The study involved 2 phases. In phase 1, the optimal position of RIP bands for recording pulmonary function was investigated in 12 control horses. In phase 2, 7 RAO-affected and 7 control horses were confined to stables. Respiratory inductance plethysmography bands were applied to horses for 24 h/d to record respiratory rate and total displacement in 4-hour periods for 7 days or until RAO-affected horses developed signs of severe RAO that persisted for 2 consecutive days. Lung function was measured once daily. RESULTS: In phase 1, thoracic and abdominal cavity displacements were best represented by RIP bands positioned at intercostal spaces 6 and 17, respectively. In phase 2, pulmonary function indicated airway obstruction in the RAO-affected group on the final 2 days of stable confinement. Respiratory rate and total degree of respiratory displacement measured by RIP did not differ between the RAO-affected and control groups, but the SDs of these decreased significantly within 8 hours after stable confinement began in RAO-affected horses. Respiratory inductance plethysmography and pulmonary function findings became highly correlated as severity of disease progressed. CONCLUSIONS AND CLINICAL RELEVANCE: The decrease in the SDs of RIP measurements indicated a lower degree of variability in breathing patterns of RAO-affected horses. This loss of variability may provide an early indicator of airway inflammation.
Asunto(s)
Enfermedades de los Caballos/patología , Enfermedades Pulmonares Obstructivas/veterinaria , Fenómenos Fisiológicos Respiratorios , Telemetría/veterinaria , Animales , Femenino , Enfermedades de los Caballos/diagnóstico , Caballos , Enfermedades Pulmonares Obstructivas/diagnóstico , Enfermedades Pulmonares Obstructivas/patología , Masculino , Respiración , Telemetría/instrumentación , Telemetría/métodosRESUMEN
Horses with intracranial lesions and severe ataxia are not good anesthesia candidates; however, only one method to obtain cerebrospinal fluid (CSF) from the cervical region in a standing horse has been reported. This method is not performed routinely due to the difficulty for sample acquisition. Our hypothesis is that standing cervical centesis can be performed in horses without complication. Ultrasound-guided centesis of the CSF between C1 and C2 in 11 clinically normal horses and two horses with neurologic signs were performed. Horses were sedated and ultrasound was used to identify the subarachnoid space and spinal cord between C1 and C2. With ultrasound guidance, a needle was introduced into the dorsal aspect of the subarachnoid space using a lateral approach. Ten milliliters of CSF was obtained and analyzed. Two normal horses in this study had moderate red blood cell contamination in the CSF (940 and 612 RBC/microl). One horse had 11 RBC/microl and the remaining horses had < 4 RBC/microl. The total procedure time was approximately 2 min. No reaction was observed and no complications were detected up to 48 h after the procedure. Ultrasound-guided centesis between C1 and C2 is a rapid procedure that causes minimal to no reaction in standing, sedated horses used in this study. The use of ultrasound to guide a standing C1-2 centesis of the subarachnoid space provides an additional route to obtain CSF for analysis in the equine patient.