Structural and functional recovery of electropermeabilized skeletal muscle in-vivo after treatment with surfactant poloxamer 188

Abstract

A critical requirement for cell survival after trauma is sealing of breaks in the cell membrane [M. Bier, S.M. Hammer, D.J. Canaday, R.C Lee, Kinetics of sealing for transient electropores in isolated mammalian skeletal muscle cells, Bioelectromagnetics 20 (1999) 194-201; R.C. Lee, D.C. Gaylor, D. Bhatt, D.A. Israel, Role of cell membrane rupture in the pathogenesis of electrical trauma, J. Surg. Res. 44 (1988) 709-719; R.C. Lee, J.F. Burke, E.G. Cravalho (Eds.), Electrical Trauma: The Pathophysiology, Manifestations, and Clinical Management, Cambridge University Press, 1992; B.I. Tropea, R.C. Lee, Thermal injury kinetics in electrical trauma, J. Biomech. Engr. 114 (1992) 241-250; F. Despa, D.P. Orgill, J. Newalder, R.C Lee, The relative thermal stability of tissue macromolecules and cellular structure in burn injury, Burns 31 (2005) 568-577; T.A. Block, J.N. Aarsvold, K.L. Matthews II, R.A. Mintzer, L.P. River, M. Capelli-Schellpfeffer, R.L. Wollman, S. Tripathi, C.T. Chen, R.C. Lee, The 1995 Lindberg Award. Nonthermally mediated muscle injury and necrosis in electrical trauma, J. Burn Care and Rehabil. 16 (1995) 581-588; K. Miyake, P.L. McNeil, Mechanical injury and repair of cells, Crit. Care Med. 31 (2003) S496-S501; R.C. Lee, L.P. River, F.S. Pan, R.L. Wollmann, Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo, Proc. Natl. Acad. Sci. 89 (1992) 4524-4528; J.D. Marks, C.Y. Pan, T. Bushell, W. Cromie, R.C. Lee, Amphiphilic, tri-block copolymers provide potent membrane-targeted neuroprotection, FASEB J. 15 (2001) 1107-1109; B. Greenebaum, K. Blossfield, J. Hannig, C.S. Carrillo, M.A. Beckett, R.R. Weichselbaum, R.C. Lee, Poloxamer 188 prevents acute necrosis of adult skeletal muscle cells following high-dose irradiation, Burns 30 (2004) 539-547; G. Serbest, J. Horwitz, K. Barbee, The effect of poloxamer-188 on neuronal cell recovery from mechanical injury, J. Neurotrauma 22 (2005) 119-132]. The triblock copolymer surfactant Poloxamer 188 (P188) is known to increase the cell survival after membrane electroporation [R.C. Lee, L.P. River, F.S. Pan, R.L. Wollmann, Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo, Proc. Natl. Acad. Sci. 89 (1992) 4524-4528; Z. Ababneh, H. Beloeil, C.B. Berde, G. Gambarota, S.E. Maier, R.V. Mulkern, Biexponential parametrization of T2 and diffusion decay curves in a rat muscle edema model: Decay curve components and water compartments, Magn. Reson. Med. 54 (2005) 524-531]. Here, we use a rat hind-limb model of electroporation injury to determine if the intravenous administration of P188 improves the recovery of the muscle function. Rat hind-limbs received a sequence of either 0, 3, 6, 9, or 12 electrical current pulses (2 A, 4 ms duration, 10 s duty cycle). Magnetic resonance imaging (MRI) analysis, muscle water content and compound muscle action potential (CMAP) amplitudes were compared. Electroporation injury manifested edema formation and depression of the CMAP amplitudes. P188 (one bolus of 1 mg/ml of blood) w...

MR Imaging to Assess Immediate Response to Irreversible Electroporation for Targeted Ablation of Liver Tissues: Preclinical Feasibility Studies in a Rodent Model

“…These IRE-induced signal alterations (ie, hyperintense zones on proton-density-and T2-weighted images and hypointense zones on T1-weighted images) were consistent with classic proton-density, T1, and T2 relaxation increases typically observed during acute episodes of tissue edema (24)(25)(26)(27). In a prior in vivo electropermeabilized skeletal muscle study, the formation of edema was qualitatively confi rmed by phase contrast photomicrographs of H-E-stained samples ( 28 ). Our fi ndings are consistent with previous gene therapy electrotransfer studies, which similarly apply high-voltage electric pulses to permeabilize cell in larger signal voids than those depicted on TSE images.…”

Long‐lasting plasma membrane permeabilization in mammalian cells by nanosecond pulsed electric field (nsPEF)

“…In agreement with these predictions, an electrical breakdown of the plasma membrane within nanoseconds after the onset of the electric pulse was demonstrated by fluorescence measurements with a voltage-sensitive dye [Frey et al, 2006]. Contrary to larger pores formed by conventional electroporation and having a lifetime of up to several minutes [Bier et al, 1999;Weaver, 2000;Collins et al, 2007], the nanopores are expected to be very short-lived. The estimates of nanopores' life span vary from nanoseconds to about 1 s maximum [Melikov et al, 2001;Vernier et al, 2003Vernier et al, , 2004Vernier et al, , 2006Gowrishankar and Weaver, 2006;Vasilkoski et al, 2006], which makes their detection problematic and their physiological significance questionable.…”

High-Pressure Transvenous Perfusion of the Upper Extremity in Human Muscular Dystrophy: A Safety Study with 0.9% Saline

“…Axonal injury was considered but the relatively rapid resolution of the reduced CMAP amplitudes and the absence of significant denervation on needle EMG refutes this. One possibility is that the reduction of amplitude was because of fluid entering the muscle and dampening the evoked response similar to electroporation reported by Collins et al 25 The time course of abnormality is not typical of that seen in ischemic injury to the nerve. 26 Given that the conduction velocities and distal latencies of the same nerves in this subject were unchanged postperfusion, and that there was no evidence for nerve/muscle impairment by history or clinical evaluation, we concluded that these electrophysiologic abnormalities were not of clinical significance.…”