Farren Adams

BACKGROUND: Traumatic brain injuries (TBIs) continue to be a devastating problem with limited treatment options. Previous research applying controlled vacuum to TBI in a rat model resulted in smaller injuries and more rapid recovery. OBJECTIVE: To examine the effects of the application of a controlled vacuum (mechanical tissue resuscitation) to TBI in a large-animal model. The magnitude of vacuum, length of application, and length of delay between injury and the application of mechanical tissue resuscitation were investigated. METHODS: Localized, controlled cortical injuries were created in swine. Vacuums of -50 and -100 mm Hg were compared. Mechanical tissue resuscitation for 3 or 5 days was compared. Delays of 0, 3, or 6 hours between the creation of the TBI and the initiation of mechanical tissue resuscitation were examined. Analysis included histological assessments, computed tomographic perfusion, and magnetic resonance imaging (T2, proton magnetic spectra). RESULTS: A -100 mm Hg vacuum resulted in significantly smaller mean contused brain and hemorrhage volumes compared with -50 mm Hg and controls. Magnetic resonance spectra of treated animals returned to near baseline values. All 10 animals with 5-day mechanical tissue resuscitation treatment survived. Three of 6 animals treated for 3 days died after the discontinuation of treatment. A 3-hour delay resulted in similar results as immediate treatment. A 6-hour delay produced significant, but lesser responses. CONCLUSION: Application of mechanical tissue resuscitation to TBI was efficacious in the large-animal model. Application of -100 mm Hg for 5 days resulted in significantly improved outcomes. Delays of up to 3 hours between injury and the initiation of treatment did not diminish the efficacy of the mechanical tissue resuscitation treatment.

Our previous studies on the treatment of spinal cord injuries with Mechanical Tissue Resuscitation (MTR) in rats have demonstrated that it can significantly improve the locomotor recovery and Basso Beattie Bresnahan scores. MTR treatment also reduced fluid accumulations by T2-imaging and improved the mean neural fiber number and fiber length in injured sites by fiber tractography. Myelin volume was also significantly preserved by MTR treatment. For further clinical application, a large animal model is necessary to assess this treatment. This study examined the effects of application of MTR on traumatic spinal cord injury in a swine model. Traumatic spinal cord contusion injuries in swine were created by controlled pneumatic impact device. Negative pressure at -75 mm Hg was continuously applied to the injured site through open cell silicone manifold for 7 days. In vivo magnetic resonance imaging for T2 and gradient echo (GRE) analysis employed a 3T machine, while a 7T machine was employed for diffusion tensor imaging (DTI) and fiber tractography. Histological hematoxylin and eosin (H&E) and Luxol fast blue staining were examined. MTR significantly reduced the mean injured volumes over 46% by T2-imaging in the injured sites from 477.34 ± 146.31 mm 3 in non-treated group to 255.99 ± 70.28 mm 3 in MTR treated group ( p < 0.01). It also reduced fluid accumulations by relative T2 signal density in the epicenter of the spinal cord injury from 1.62 ± 0.27 in non-treated group to 1.22 ± 0.10 in the MTR treated group ( p < 0.05). The mean injured tissue volume measured by H&E staining was 303.71 ± 78.21 mm 3 in the non-treated group and decreased significantly to 162.16 ± 33.0 mm 3 in the MTR treated group ( p < 0.01). The myelin fiber bundles stained by Luxol blue were preserved much more in the MTR treated group (90 ± 29.71 mm 3 ) than in the non-treated group (33.68 ± 24.99 mm 3 , p < 0.01). The fractional anisotropy (FA) values processed by DTI analysis are increased from 0.203 ± 0.027 in the untreated group to 0.238 ± 0.029 in MTR treatment group ( p < 0.05). Fiber tractography showings the mean fiber numbers across the impacted area were increased over 112% from 327.0 ± 99.74 in the non-treated group to 694.83 ± 297.86 in the MTR treated group ( p < 0.05). These results indicate local application of MTR for 7 days to spinal cord injury in a swine model decreased tissue injury, reduced tissue edema, and preserved more myelin fibers as well as nerve fibers in the injured spinal cord.

OBJECTIVE: The previous laboratory and clinical experience of the authors had demonstrated that application of controlled subatmospheric pressure directly to injured soft tissue can result in increased survival of compromised tissues. Mechanical tissue resuscitation (MTR) is a new concept evolving from these discoveries. The authors' recent studies have demonstrated that traumatic brain injury tissue can also be salvaged. The aim of this study was to examine the effects of MTR application to injuries from intracerebral hemorrhages (ICHs) in a swine model. METHODS: The ICHs in swine were simulated by infusion of autologous artery blood into the right frontal lobe. A specially designed silicone manifold device was introduced directly into the hematoma. Continuous negative pressure at -50 mm Hg was applied through this device. T2- and T2*-weighted MRI, histological H&E staining, and immunostaining were examined. RESULTS: After 1 week of treatment, MTR significantly decreased gross hematoma volume by more than 60%, from 472.62 ± 230.19 mm3 in the nontreated group to 171.25 ± 75.38 mm3 in the MTR-treated group (p < 0.05). Total hypointense volumes measured on T2*-weighted MR images decreased from 791.99 ± 360.47 mm3 in the nontreated group to 371.16 ± 105.75 mm3 in the MTR-treated group (p < 0.05). The hyperintense area on the T2-weighted MR image decreased significantly from 2656.23 ± 426.26 mm3 in the nontreated group to 1816.66 ± 525.26 mm3 in the MTR-treated group (p < 0.05). When ICHs were treated with MTR for 2 weeks, the gross hematomas were reduced by 94%, from 112.23 ± 66.21 mm3 in the nontreated group to 6.12 ± 10.99 mm3 in the MTR-treated group (p = 0.003). MTR significantly decreased the total necrotic tissue volume in H&E staining from 120.42 ± 48.35 mm3 in the nontreated group to 60.94 ± 38.99 mm3 in the MTR-treated group (p < 0.05). The total hypointense volumes on T2*-weighted MR images were significantly reduced, from 385.54 ± 93.85 mm3 in the nontreated group to 220.54 ± 104.28 mm3 in the MTR-treated group (p < 0.05), while their mean T2 hyperintense volume decreased significantly from 2192.83 ± 728.27 mm3 in the nontreated group to 1366.97 ± 463.36 mm3 in the MTR-treated group (p < 0.05). Histology revealed that the capillary diameter in the reactive tissue rim adjacent to the hematoma increased in both the 1- and 2-week MTR-treated groups. Both von Willebrand factor and CD31 signals were detectable in endothelial cells within the hematoma cavity of both MTR-treated groups. CONCLUSIONS: This study demonstrates that local continuous application of controlled subatmospheric pressure to an ICH can safely remove more than half of a clot in 1 week and more than 90% in 2 weeks.