Novel treatment of intracerebral hemorrhage with mechanical tissue resuscitation

Abstract

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.