EMPulse Abstracts

Healing Tools & EMpulse / PEMF Abstracts

(REFERENCE 1 OF 9)

THE NASA STUDY
“PHYSIOLOGICAL AND MOLECULAR GENETIC EFFECTS OF TIME-VARYING ELECTROMAGNETIC FIELDS ON HUMAN NEURONAL CELLS” (SEPTEMBER 2003) (NASA/TP-2003-212054)

NASA 4-year collaborative study on the efficacy of electromagnetic fields to stimulate growth and repair in mammalian tissues NASA/TP-2003-212054*
http://ston.jsc.nasa.gov/collections/TRS/_techrep/TP-2003-212054.pdf

CHIEF INVESTIGATORS:
Robert Dennis, PhD - University of Michigan, Ann Arbor, MI, USA
Thomas J. Goodwin, PhD - NASA Johnson Space Center (JSC), Houston, TX, USA

PURPOSE
This four-year study used human donors to “define the most effective electromagnetic fields for enhancing growth and repair in mammalian tissues.”

The study wanted to utilize “nerve tissue which has been refractory to efforts to stimulate growth or enhance its repair regardless of the energy used.” (All other tissues have demonstrated growth and repair stimulation with appropriate PEMF.)

In addition, the study attempted to define a PEMF technology that would “duplicate mature, three-dimensional morphology between neuronal cells and feeder (glial) cells, which has not been previously accomplished.”

STUDY RESULTS
The PEMF used in the study “caused accelerated growth rate and better organized morphology over controls” and resulted in “greater cell viability” (85% vs. 65%). In the gene discovery array (chip technology that surveyed 10,000 human genes), the investigators found up-regulation of 150 genes associated with growth and cell restoration.

NASA’S RECOMMENDATIONS

“One may use square wave EM fields with rapid rate of change" for:

REPAIRING TRAUMATIZED TISSUES
MODERATING SOME NEURODEGENERATIVE DISEASES
DEVELOPING TISSUES FOR TRANSPLANTATION

NASA’S CONCLUSIONS:

“The up-regulation of these genes is in no manner marginal (1.7-8.4 logs) with gene sites for collagen production and growth the most actively stimulated.”

“We have clearly demonstrated the bioelectric/biochemical potentiation of nerve stimulation and restoration in humans as a documented reality.”

“The most effective electromagnetic field for repair of trauma was square wave with a rapid rate of change (dB/dt) which saw cell growth increased up to 4.0 times.”

NASA further noted that “slowly varying (millisecond pulse, sine wave) or non varying DC (CW lasers, magnets) had little to no effect.”

*NASA’s study is the first to clarify technologies and efficacy parameters for tissue growth and restoration.

NASA PEMF STUDY ABSTRACT

“The present investigation details the development of model systems for growing two- and three-dimensional human neural progenitor cells within a culture medium facilitated by a time-varying electromagnetic field (TVEMF). The cells and culture medium are contained within a two- or three-dimensional culture vessel, and the electromagnetic field is emitted from an electrode or coil. These studies further provide methods to promote neural tissue regeneration by means of culturing the neural cells in either configuration. Grown in two dimensions, neuronal cells extended longitudinally, forming tissue strands extending axially along and within electrodes comprising electrically conductive channels or guides through which a time-varying electrical current was conducted. In the three-dimensional aspect, exposure to TVEMF resulted in the development of three-dimensional aggregates, which emulated organized neural tissues. In both experimental configurations, the proliferation rate of the TVEMF cells was 2.5 to 4.0 times the rate of the non-waveform cells. Each of the experimental embodiments resulted in similar molecular genetic changes regarding the growth potential of the tissues as measured by gene chip analyses, which measured more than 10,000 human genes simultaneously.” (Page 1) (NASA/TP-2003-212054)

View Study PDF on NASA’s Technical Reports Server (NTRS)

(REFERENCE 2 OF 9)

Jrnl of Orthopaedic Research. 2004 Jan; 22 (1): 80-4. “Microcirculatory Effects of Pulsed Electromagnetic Fields (PEMF).” Smith TL, Wong-Gibbons D, Maultsby J. Department of Orthopaedic Surgery, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC, USA.

Pulsed electromagnetic fields (PEMF) are used clinically to expedite healing of fracture non-unions, however, the mechanism of action by which PEMF stimulation is effective is unknown. The current study examined the acute effects of PEMF stimulation on arteriolar microvessel diameters in the rat cremaster muscle. The study hypothesis was that PEMF would increase arteriolar diameters, a potential mechanism involved in the healing process. METHODS: Local PEMF stimulation/sham stimulation of 2 or 60 min duration was delivered to the cremaster muscle of anesthetized rats. Arteriolar diameters were measured before and after stimulation/sham stimulation using intravital microscopy. Systemic hemodynamics also were monitored during PEMF stimulation. RESULTS: Local PEMF stimulation produced significant (p<0.001) vasodilation, compared to pre-stimulation values, in cremasteric arterioles in anesthetized rats (n=24). This dilation occurred after 2 min of stimulation (9% diameter increase) and after 1 h of stimulation (8.7% diameter increase). Rats receiving “sham” stimulation (n=15) demonstrated no statistically significant change in arteriolar diameter following either “sham” stimulation period. PEMF stimulation of the cremaster (n=4 rats) did not affect systemic arterial pressure or heart rate, nor was it associated with a change in tissue environmental temperature. CONCLUSIONS: These results support the hypothesis that local application of a specific PEMF waveform can elicit significant arteriolar vasodilation. Systemic hemodynamics and environmental temperature could not account for the observed microvascular responses.

(REFERENCE 3 OF 9)

Bioelectromagnetics. 2003 Sep; 24 (6): 373-9. “The Effect of Exposure to High Flux Density Static and Pulsed Magnetic Fields on Lymphocyte Function.” Aldinucci C, Garcia JB, Palmi M, Sgaragli G, Benocci A, Meini A, Pessina F, Rossi C, Bonechi C, Pessina GP. Department of Physiology, University of Siena, Italy.

We investigated whether a combination of static electromagnetic field (EMF) at a flux density of 4.75 T together with pulsed EMF at a flux density of 0.7 mT generated by an NMR apparatus (NMRF), could promote movements of Ca(2+), cell proliferation, and the eventual production of proinflammatory cytokines in human lymphocytes as well as in Jurkat cells, after exposure to the field for 1 h. The same study was also performed after activation of cells with 5 micro g/ml phytohaemagglutinin (PHA) immediately before the exposure period. Our results clearly demonstrate that NMRF exposure increases the [Ca(2+)](i), without any proliferative, or activating, or proinflammatory effect on both normal and PHA stimulated lymphocytes. Accordingly, the levels of interferon gamma, tumor necrosis factor alpha, interleukin-1beta, interleukin-2, and interleukin-6 remained unvaried after exposure. Exposure of Jurkat cells statistically decreased the [Ca(2+)](i) and the proliferation. This is consistent with the low levels of IL-2 measured in supernatants of these cells after exposure. On the whole our data suggest that static and pulsed NMRF exposure contribute synergistically in the increase of the [Ca(2+)](i) without any activating or proinflammatory effect either in normal or in PHA challenged lymphocytes. In Jurkat cells, by changing the properties of cell membranes, NMRF exposure can influence Ca(2+) transport processes and hence Ca(2+) homeostasis, causing a marked decrease of proliferation.

(REFERENCE 4 OF 9)

Experimental and Molecular Medicine. 2002 Mar 31; 34 (1): 53-9. “Enhanced Expression of Neuronal Nitric Oxide Synthase and Phospholipase C-gamma1 in Regenerating Murine Neuronal Cells by Pulsed Electromagnetic Field.” Kim SS, Shin HJ, Eom DW, Huh JR, Woo Y, Kim H, Ryu SH, Suh PG, Kim MJ, Kim JY, Koo TW, Cho YH, Chung SM. Department of Pathology, Ulsan University College of Medicine, South Korea.

Pulsed electromagnetic field (PEMF) has been shown to improve the rate of peripheral nerve regeneration. In the present study we investigated the expression of neuronal nitric oxide synthase (nNOS) and phospholipase C-gamma1 (PLC-gamma1) in regenerating rat laryngeal nerves during the exposure to PEMF after surgical transection and reanastomosis. Axons were found to regenerate into the distal stump nearly twice faster in PEMF-exposed animals than in the control. Consistently, motor function was better recovered in PEMF-treated rats. The expression of nNOS and PLC-gamma1 was highly enhanced in the regenerated nerves.

(REFERENCE 5 OF 9)

Biophysical Journal. 1996 Aug; 71 (2): 623-31. “Model for Magnetic Field Effects on Radical Pair Recombination in Enzyme Kinetics.” Eichwald C, Walleczek J. Department of Radiation Oncology, School of Medicine, Stanford Univ., CA, USA.

A prototypical model for describing magnetic field effects on the reaction kinetics of enzymes that exhibit radical pair recombination steps in their reaction cycle is presented. The model is an extended Michaelis-Menten reaction scheme including an intermediate enzyme-substrate complex where a spin-correlated radical pair state exists. The simple structure of the scheme makes it possible to calculate the enzyme reaction rate explicitly by combining chemical kinetics with magnetic field-dependent spin kinetics (radical pair mechanism). Recombination probability is determined by using the exponential model. Simulations show that the size of the magnetic field effect depends on relations between different rate constants, such as: 1) the ratio between radical pair-lifetime and the magnetic field-sensitive intersystem crossing induced by the hyperfine interaction and the delta g mechanisms and 2) the chemical rate constants of the enzyme reaction cycle. An amplification factor that is derived from the specific relations between the rate constants is defined. It accounts for the fact that although the magnetic field-induced change in radical pair recombination probability is very small, the effect on the enzyme reaction rate is considerably larger, for example, by a factor of 1 to 100. Model simulations enable a qualitative comparison with recent experimental studies reporting magnetic field effects on coenzyme B12-dependent ethanolamine ammonia lyase in vitro activity that revealed a reduction in Vmax/KM at low flux densities and a return to the zero-field rate or an increase at high flux densities.

(REFERENCE 6 OF 9)

Bioelectromagnetics. 1994; 3 (15): 205-216. “Protection Against Focal Cerebral Ischemia Following Exposure to a Pulsed Electromagnetic Field.” Grant G., Cadossi R., Steinberg G. Department of Neurosurgery, Stanford Univ., CA, USA.

There is evidence that electromagnetic stimulation may accelerate the healing of tissue damage following ischemia. We undertook this study to investigate the effects of low frequency pulsed electromagnetic field (PEMF) exposure on cerebral injury in a rabbit model of transient focal ischemia (2 h occlusion followed by 4 h of reperfusion). PEMF exposure (280 V, 75 Hz, IGEA Stimulator) was initiated 10 min after the onset of ischemia and continued throughout reperfusion (six exposed, six controls). Magnetic resonance imaging (MRI) and histology were used to measure the degree of ischemic injury. Exposure to pulsed electromagnetic field attenuated cortical ischemia edema on MRI at the most anterior coronal level by 65% (P < 0.001). On histologic examination, PEMF exposure reduced ischemic neuronal damage in this same cortical area by 69% (P < 0.01) and by 43% (P < 0.05) in the striatum. Preliminary data suggest that exposure to a PEMF of short duration may have implications for the treatment of acute stroke.

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Jrnl Cell Biochem. 1993 Apr; 51 (4): 387-393. “Beneficial Effects of Electromagnetic Fields.” Bassett C.A. Bioelectric Research Center, Columbia Univ., NY, USA.

Selective control of cell function by applying specifically configured, weak, time-varying magnetic fields has added a new, exciting dimension to biology and medicine. Field parameters for therapeutic, pulsed electromagnetic field (PEMFs) were designed to induce voltages similar to those produced, normally, during dynamic mechanical deformation of connective tissues. As a result, a wide variety of challenging musculoskeletal disorders have been treated successfully over the past two decades. More than a quarter million patients with chronically ununited fractures have benefitted, worldwide, from this surgically non-invasive method, without risk, discomfort, or the high costs of operative repair. Many of the athermal bioresponses, at the cellular and subcellular levels, have been identified and found appropriate to correct or modify the pathologic processes for which PEMFs have been used. Not only is efficacy supported by these basic studies but by a number of double-blind trials. As understanding of mechanisms expands, specific requirements for field energetics are being defined and the range of treatable ills broadened. These include nerve regeneration, wound healing, graft behavior, diabetes, and myocardial and cerebral ischemia (heart attack and stroke), among other conditions. Preliminary data even suggest possible benefits in controlling malignancy.

(REFERENCE 8 OF 9)

Jrnl Cell Biochem. 1993 Apr; 51 (4): 404-9. “Prospects on Clinical Applications of Electrical Stimulation for Nerve Regeneration.” Sisken BF, Walker J, Orgel M. Center for Biomedical Engineering, University of Kentucky, Lexington, KY, USA.

PURPOSE: Regenerative capability is limited in higher vertebrates but present in organ systems such as skin, liver, bone, and to some extent, the nervous system. Peripheral nerves in particular have a relatively high potential for regeneration following injury. However, delay in regrowth or growth, blockage, or misdirection at the injury site, and growth to inappropriate end organs may compromise successful regeneration, leading to poor clinical results. Recent studies indicate that low-intensity electrical stimulation is equivalent to various growth factors, offering avenues to improve these outcomes. We present a review of studies using electric and electromagnetic fields that provide evidence for the enhancement of regeneration following nerve injury. Electric and electromagnetic fields (EMFs) have been used to heal fracture non-unions. This technology emerged as a consequence of basic studies [Yasuda, 1953; Fukada and Yasuda, 1957] demonstrating the piezoelectric properties of (dry) bone. The principle for using electrical stimulation for bone healing originated from the work of Bassett and Becker [1962], who described asymmetric voltage waveforms from mechanically deformed live bone. These changes were presumed to occur in bone during normal physical activity as a result of mechanical forces, and it was postulated that these forces were linked to modifications in bone structure. Endogenous currents present in normal tissue and those that occur after injury were proposed to modify bone structure [Bassett, 1989]. These investigators proposed that tissue integrity and function could be restored by applying electrical and/or mechanical energy to the area of injury. They successfully applied electrical currents to nonhealing fractures (using surgically implanted electrodes or pulsed currents using surface electrodes) to aid endogenous currents in the healing process. (Abstract truncated at 250 words.)

(REFERENCE 9 OF 9)

FASEB J. 1992 Oct; 6(13): 3177-85. “Electromagnetic Field Effects on Cells of the Immune System: The Role of Calcium Signaling.” Walleczek J. Research Medicine and Radiation Biophysics Division, Lawrence Berkeley Laboratory, University of California, Berkeley, CA, USA.

During the past decade considerable evidence has accumulated demonstrating that nonthermal exposures of cells of the immune system to extremely low-frequency (ELF) electromagnetic fields (<300 Hz) can elicit cellular changes that might be relevant to in vivo immune activity. A similar responsiveness to nonionizing electromagnetic energy in this frequency range has also been documented for tissues of the neuroendocrine and musculoskeletal system. However, knowledge about the underlying biological mechanisms by which such fields can induce cellular changes is still very limited. It is generally believed that the cell membrane and Ca(2+)-regulated activity is involved in bioactive ELF field coupling to living systems. This article begins with a short review of the current state of knowledge concerning the effects of nonthermal levels of ELF electromagnetic fields on the biochemistry and activity of immune cells and then closely examines new results that suggest a role for Ca2+ in the induction of these cellular field effects. Based on these findings it is proposed that membrane-mediated Ca2+ signaling processes are involved in the mediation of field effects on the immune system.