Contribution of inflammation to cellular injury in compartment syndrome in an experimental rodent model.

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.

The effect of ischemia reperfusion injury on skeletal muscle.

Ischemia reperfusion (IR) injury occurs when tissue is reperfused following a period of ischemia, and results from acute inflammation involving various mechanisms. IR injury can occur following a range of circumstances, ranging from a seemingly minor condition to major trauma. The intense inflammatory response has local as well as systemic effects because of the physiological, biochemical and immunological changes that occur during the ischemic and reperfusion periods. The sequellae of the cellular injury of IR may lead to the loss of organ or limb function, or even death. There are many factors which influence the outcome of these injuries, and it is important for clinicians to understand IR injury in order to minimize patient morbidity and mortality. In this paper, we review the pathophysiology, the effects of IR injury in skeletal muscle, and the associated clinical conditions; compartment syndrome, crush syndrome, and vascular injuries.

[Muscular compartment syndrome of the forearm in a haemophilia inhibitor patient]. / Das muskuläre Kompartmentsyndrom am Unterarm bei Hemmkörperhämophilie.

UNLABELLED: Acute compartment syndrome is a complication in which microcirculation is impaired due to increased tissue pressure within a confined (osteo-fibrous) space and leads to neuromuscular dysfunction. A serious complication of haemophilia is the development of inhibitors. In this case the immune system produces antibodies to factor VIII or IX during substitution therapy of haemophilia A or B. These antibodies are directed against both, the substituted and the endogenous factors. CASE REPORT: A man (age: 81 years) with originally moderate haemophilia A who at the age of 63 developed an inhibitor during treatment of a bleeding event. Painful swelling in the left forearm occurred without any recollection of trauma, and failed to subside under factor substitution initially performed by the patient. This finding necessitated emergency fasciotomy of the forearm flexor compartment. CONCLUSION: In order to keep the complication rate as low as possible in the presence of hemophilia with inhibitors, the patients should only be treated in a specially equipped interdisciplinary treatment center.

[Influence of V.A.C.-therapy on cytokines and growth factors in traumatic wounds]. / Einfluss der V.A.C.-Therapie auf Zytokine und Wachstumsfaktoren in Traumatischen Wunden.

OBJECTIVE: Clinical observations have shown an accelerated wound healing in wounds of patients treated by Vacuum Assisted Closure (V.A.C.)-therapy. The mechanisms of improved wound healing on cellular level have been hitherto less investigated. In this study the levels of proinflammatory interleukins (IL-6, IL-8, IL-10) and growth factors (VEGF, FGF-2) in serum and wound were monitored. METHODS: The study included 21 patients with traumatic wounds that could not be closed during the first surgical intervention. The soft tissue defects (n = 21) were closed temporarily by Epigard. During the first second-look operation after 2.0 +/- 0.2 days in an average, Epigard was used for another 2.5 +/- 0.4 days as temporary soft tissue coverage in 13 patients (group A). In the remaining 8 patients the wound conditioning was done by V.A.C.(R) for 2.4 +/- 0.3 days (group B). A total of 428 samples of serum and wound fluid samples were collected during the first and second look operation. Levels of IL-6, IL-8, IL-10, VEGF and FGF were measured specific by ELISA. RESULTS: In all interleukins and growth factors there were significant lower serum level concentrations compared with those in wound fluids. During the first temporary dressing change after wound coverage with Epigard the wound samples showed the following levels [Mean (SEM)]: IL-6 49 816 (19 889) pg/ml, IL-8 54 (16) ng/ml, IL-10 314 (44) pg/ml, VEGF 4 746 (766) pg/ml, FGF-2 494 (89) pg/ml. During the second dressing changes we monitored the following levels in group A: IL-6 7 218 (2 542) pg/ml, IL-8 69 (27) ng/ml, IL-10 261 (58) pg/ml, VEGF 3 551 (661) pg/ml, FGF-2 355 (67) pg/ml. In group B the samples of the wound fluid showed the following results: IL-6 16 966 (4 124) pg/ml [p = 0.02], IL-8 223 (91) ng/ml [p = 0.03], IL-10 233 (76) pg/ml [p = 0.38], VEGF 7 490 (1 565) pg/ml [p = 0.01], FGF-2 352 (43) pg/ml [p = 0.48]. CONCLUSION: The increased local release of IL-6, IL-8 and VEGF in wounds after V.A.C.-therapy may be involved in the accumulation of neutrophil granulocytes and angiogenesis, which seams to play a crucial role for the accelerated granulation tissue formation after V.A.C.-therapy compared to wounds treated by Epigard.

[Suppression of neutrophil immune function in rabbit models of hemorrhagic shock complicated by intra-abdominal hypertension].

OBJECTIVE: To investigate the effects of hemorrhagic shock and intra-abdominal hypertension (IAH) on inflammatory responses of peripheral circulating neutrophils such as intracellular cytokine production, phagocytic capacity and expression of nuclear factor (NF)- kappaB. METHODS: Twenty-four rabbits were divided equally into 4 groups including a hemorrhagic shock (HS) group complicated by abdominal compartment syndrome (ACS) (Group A), a HS group (Group B), a ACS group (Group C) and a normal control group (Group D). Intracellular interleukin (IL)-8 production in the peripheral neutrophils were measured in the rabbits by flow cytometry, phagocytic function of the neutrophils evaluated by a chemiluminescence method and the NF-kappaB expression detected by immunocytochemistry before, immediately and 4 h after the traumatization. RESULTS: Four hours after the trauma, decreased intracellular IL-8 production and impaired phagocytic function of the peripheral neutrophils were observed in Group A along with suppressed NF-kappaB expression. But in Group B and Group C, the intracellular IL-8 production, phagocytic function and expression of NF-kappaB returned to the normal levels 4 hours after the trauma following the early-stage changes. In Group D, no significant changes occurred during the observation. CONCLUSIONS: Responsiveness and function of the neutrophils to the stimuli by endotoxin are suppressed by the sequential second-hit of IAH after hemorrhagic shock, which may contribute to the occurrence of sepsis in ACS.

Amplified cytokine response and lung injury by sequential hemorrhagic shock and abdominal compartment syndrome in a laboratory model of ischemia-reperfusion.

BACKGROUND: Increased intra-abdominal pressure has been shown to result in a myriad of physiologic aberrations that result in the abdominal compartment syndrome (ACS). The clinically relevant combination of hemorrhagic shock and resuscitation and subsequent ACS, however, has not been studied in detail. We hypothesized that sequential hemorrhagic shock (HS) and ACS would result in greater cytokine activation and polymorphonuclear neutrophil (PMN)-mediated lung injury than with either insult alone. METHODS: Twenty Yorkshire swine (20-30 kg) were studied. Group 1 (n = 5) was hemorrhaged to a mean arterial pressure of 25 to 30 mm Hg for 60 minutes and resuscitated to baseline mean arterial pressure. Intra-abdominal pressure was then increased to 30 mm Hg above baseline and maintained for 60 minutes. Group 2 (n = 5) was subjected to HS alone and Group 3 (n = 5) to ACS alone. Group 4 (n = 5) had sham experiment without HS or ACS. Central and portal venous interleukin-1beta, interleukin-8, and tumor necrosis factor-alpha levels were serially measured. Bronchoalveolar lavage (BAL) for protein and PMNs was performed at baseline and 24 hours after resuscitation. Lung myeloperoxidase was evaluated at 24 hours after resuscitation. RESULTS: Portal and central vein cytokine levels were equivalent but were significantly higher in Group 1 than in other groups. BAL PMNs were higher (p < 0.05) in Group 1 (4.1 +/- 2.0 x 106) than in the other groups (0.6 +/- 0.5, 1.4 +/- 1.3, and 0.1 +/- 0.0 x 106, respectively) and lung myeloperoxidase activity was higher (p < 0.05) in Group 1 (134.6 +/- 57.6 x 106/g) than in the other groups (40.3 +/- 14.7, 46.1 +/- 22.4, and 7.73 +/- 4.4 x 106/g, respectively). BAL protein was higher (p < 0.01) in Group 1 (0.92 +/- 0.32 mg/mL) compared with the other groups (0.22 +/- 0.08, 0.29 +/- 0.11, and 0.08 +/- 0.06 mg/mL, respectively). CONCLUSION: In this clinically relevant model, sequential insults of ischemia-reperfusion (HS and resuscitation) and ACS were associated with significantly increased portal and central venous cytokine levels and more severe lung injury than HS or ACS alone.

Neutrophil mediated microvascular injury in acute, experimental compartment syndrome.

The purpose of this study was to determine the contribution of neutrophils and tissue xanthine oxidase to the skeletal muscle microvascular dysfunction in an ex vivo model of acute compartment syndrome. Adult dogs were rendered neutropenic or depleted of tissue xanthine oxidase before gracilis muscle isolation. Compared with continuously perfused, nonischemic muscles, acute, experimental compartment syndrome resulted in a dramatic increase in microvascular permeability, muscle neutrophil content, and muscle vascular resistance. Neutropenia prevented, whereas xanthine oxidase depletion had no effect on, the microvascular dysfunction and muscle neutrophil infiltration elicited by experimental compartment syndrome. These results suggest that neutrophils contribute to the microvascular dysfunction and blood flow distribution abnormalities elicited by acute, experimental compartment syndrome.