RESUMEN
AIMS: Compartment syndrome results from increased intra-compartmental pressure (ICP) causing local tissue ischaemia and cell death, but the systemic effects are not well described. We hypothesised that compartment syndrome would have a profound effect not only on the affected limb, but also on remote organs. METHODS: Using a rat model of compartment syndrome, its systemic effects on the viability of hepatocytes and on inflammation and circulation were directly visualised using intravital video microscopy. RESULTS: We found that hepatocellular injury was significantly higher in the compartment syndrome group (192 PI-labelled cells/10(-1) mm(3), standard error of the mean (sem) 51) compared with controls (30 PI-labelled cells/10(-1) mm(3), sem 12, p < 0.01). The number of adherent venular white blood cells was significantly higher for the compartment syndrome group (5 leukocytes/30s/10 000 µm(2), sem 1) than controls (0.2 leukocytes/30 s/10 000 µm(2), sem 0.2, p < 0.01). Volumetric blood flow was not significantly different between the two groups, although there was an increase in the heterogeneity of perfusion. CONCLUSIONS: Compartment syndrome can be accompanied by severe systemic inflammation and end organ damage. This study provides evidence of the relationship between compartment syndrome in a limb and systemic inflammation and dysfunction in a remote organ. Cite this article: Bone Joint J 2016; 98-B:1132-7.
Asunto(s)
Síndromes Compartimentales/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Animales , Velocidad del Flujo Sanguíneo/fisiología , Muerte Celular , Síndromes Compartimentales/patología , Síndromes Compartimentales/fisiopatología , Modelos Animales de Enfermedad , Hepatocitos/patología , Leucocitos/fisiología , Hígado/irrigación sanguínea , Circulación Hepática/fisiología , Masculino , Microcirculación/fisiología , Ratas Wistar , Daño por Reperfusión/complicaciones , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Compartment syndrome, a devastating consequence of limb trauma, is characterised by severe tissue injury and microvascular perfusion deficits. We hypothesised that leucopenia might provide significant protection against microvascular dysfunction and preserve tissue viability. Using our clinically relevant rat model of compartment syndrome, microvascular perfusion and tissue injury were directly visualised by intravital video microscopy in leucopenic animals. We found that while the tissue perfusion was similar in both groups (38.8% (standard error of the mean (sem) 7.1), 36.4% (sem 5.7), 32.0% (sem 1.7), and 30.5% (sem 5.35) continuously-perfused capillaries at 45, 90, 120 and 180 minutes compartment syndrome, respectively versus 39.2% (sem 8.6), 43.5% (sem 8.5), 36.6% (sem 1.4) and 50.8% (sem 4.8) at 45, 90, 120 and 180 minutes compartment syndrome, respectively in leucopenia), compartment syndrome-associated muscle injury was significantly decreased in leucopenic animals (7.0% (sem 2.0), 7.0%, (sem 1.0), 9.0% (sem 1.0) and 5.0% (sem 2.0) at 45, 90, 120 and 180 minutes of compartment syndrome, respectively in leucopenia group versus 18.0% (sem 4.0), 23.0% (sem 4.0), 32.0% (sem 7.0), and 20.0% (sem 5.0) at 45, 90, 120 and 180 minutes of compartment syndrome in control, p = 0.0005). This study demonstrates that the inflammatory process should be considered central to the understanding of the pathogenesis of cellular injury in compartment syndrome.
Asunto(s)
Síndromes Compartimentales/fisiopatología , Inflamación/fisiopatología , Leucopenia/fisiopatología , Músculo Esquelético/inmunología , Animales , Hipoxia de la Célula/inmunología , Síndromes Compartimentales/inmunología , Modelos Animales de Enfermedad , Inflamación/inmunología , Leucocitos/inmunología , Leucopenia/inmunología , Masculino , Microcirculación , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/patología , Necrosis/inmunología , Ratas , Ratas WistarRESUMEN
OBJECTIVES: The liver has been shown to play a particularly important role in the initiation and progression of the early systemic inflammatory response (SIR) to spinal cord injury (SCI). The purpose of this study was to determine the time course of leucocyte recruitment to the liver, and to determine the effect of injury severity on the magnitude of leucocyte recruitment and hepatic injury. METHODS: Rats were randomly assigned to one of the following groups: uninjured, sham-injured (laminectomy and no cord injury), cord compressed or cord transected. At 30 min and 90 min after SCI rats had the left lobe of their livers externalised and visualised using intravital video microscopy. RESULTS: Thirty minutes after injury the total number of leucocytes per post-sinusoidal venule was significantly increased after cord transection compared to that in uninjured and sham-injured rats (P<0.05). Of these leucocytes, significantly more were adherent to venule walls (P<0.05). At 90 min the total number of leucocytes per post-sinusoidal venule and the number of adherent and rolling leucocytes was significantly increased after cord transection and cord compression (P<0.05). DISCUSSION: This is the first study to use intravital microscopy to visualise systemic inflammation in the liver following SCI. We have demonstrated immediate leucocyte recruitment to the liver within 30 min after injury and have shown that systemic inflammation increases with time after injury and with severity of injury.