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Surfactant Chaperone P188 Seals Electroporated Muscle Membranes
Author(s) -
Collins J.,
Gissel H.,
Mustafi D.,
Rojahn K.,
Despa F.,
Lee R.C.
Publication year - 2008
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.130216i.x
Subject(s) - voxel , medicine , electroporation , biomedical engineering , nuclear medicine , edema , anesthesia , chemistry , materials science , nuclear magnetic resonance , surgery , radiology , physics , biochemistry , gene
Electric fields of the magnitude likely to occur in electrical injury can result in skeletal muscle electroporation. It has been reported that Poloxamer 188 (P188) is able to seal damaged cell membranes. Using a previously described rat hind limb model of electrical injury, in this study we employ MRI to demonstrate that intravenously administered P188 arrests muscle tissue edema caused by electrical shock. Methods: Anesthetized Sprague‐Dawley rat hindlimbs were subjected to 12 electrical shock pulses of 2 kV and ∼2A amplitude with duration of 4 ms. There was a 10‐second separation period between shocks to allow thermal relaxation. Animals received either P188 or Lactated Ringer’s Injection (control) intravenously at 60 minutes after shock. Proton MRI were recorded using a 4.7‐Tesla Bruker scanner (200 MHz). A Multi‐Slice Multi‐Echo (MSME) spin echo sequence was used to obtain T 2 ‐weighted images. Ten slices over the entire midthigh region were taken. For each slice, images from 10 echos in the TE range of 10 ms–100 ms and TR = 2000 ms were collected. Imaging began at 60 minutes and continued until 3 hours postshock. The signal intensities at different TE times were used to fit an exponential decay and measure the T 2 value in each voxel. Voxels with T 2 values > 80 ms were considered injured. Results: There were noticeable increases of injured area with time for electrically injured limbs due to development of edema. Control‐treated rats averaged a 58.0%(±6.59% SD) increase in total area of injury. The total area of injury for P188‐treated rats increased by 46.6%(±2.96% SD) In nonelectroporation limbs, no change in T 2 occurred. Discussion: Disruption of the plasma membrane due to electrical current leads to edema. We treated the injured muscles with P188 and observed that it helped to arrest edema. MRI proved effective not only in characterizing the degree of injury resulting from electrical shock but also in monitoring therapeutic efficacy. [Supported by the National Institutes of Health (GM61101)]