Effect of anodal & cathodal fields of direct current on some biochemical events in sheep liver.
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INTRODUCTION: High atrial defibrillation energy requirements (ADER) in patients with chronic atrial fibrillation (AF) may limit the acceptance of transvenous atrial defibrillation. We evaluated an optimized defibrillation electrode configuration that could help to reduce the ADER in patients with AF. METHODS AND RESULTS: We tested ten different configurations in nine dogs with AF (3.33+/-2.92 days) induced by rapid atrial pacing. The configurations were: right atrial (RA) appendage as anode and coronary sinus (CS) as cathode; RA and innominate vein (I) as anode to CS (cathode); RA-CS (anode) to I (cathode); I-CS (anode) to RA (cathode); RA and left lateral subcutaneous patch (P) as anode to CS (cathode); RA-CS (anode) to P (cathode); P-CS (anode) to RA (cathode); superior vena cava (SVC) and CS (anode) to RA (cathode); RA-CS (anode) to SVC (cathode); and RA-SVC (anode) to CS (cathode). ADER was defined as the voltage needed to defibrillate the atria in 10% to 90% of 20 consecutive shocks. Three lead systems had ADER lower than the RA (anode) to CS (cathode) configuration, which required a mean of 143+/-58 volts. These three were: RA-SVC (anode) to CS (cathode) 103+/-29 V; I-CS (anode) to RA (cathode) 129+/-39 V; and P-CS (anode) to RA (cathode) 130+/-38 V. The remaining configurations had ADER higher than the RA (anode) to CS (cathode) configuration. CONCLUSION: Adding an additional shocking electrode may reduce ADER when compared with the RA (anode) to CS (cathode) configuration. This concept could be incorporated into future implantable atrial defibrillators or used for refractory patients undergoing temporary transvenous cardioversion.
Electric fields (EFs) resembling those in the developing and regenerating nervous systems steer growth cones towards the cathode. Requirements for actin microfilaments, microtubules and their interactions during EF growth cone steering have been presumed, but remain unproven. Here, we demonstrate essential roles for dynamic microfilaments and microtubules in cathode-directed migration. Cathodal turning of growth cones on cultured Xenopus embryonic spinal neurons was attenuated significantly by nanomolar concentrations of the microfilament inhibitor latrunculin, the microtubule-stabilising drug taxol, or the microtubule-destabilising drugs vinblastine or nocodazole. Dynamically, the cathodal bias of filopodia preceded cathodal turning of the growth cone, suggesting an instructive role in EF-induced steering. Lamellipodial asymmetry accompanied turning. Filopodia and lamellipodia are regulated by the GTPases Cdc42 and Rac, respectively, and, as shown in the companion paper in this issue, peptides that selectively prevented effector binding to the CRIB domains of Cdc42 or Rac abolished cathodal growth cone turning during 3 hours of EF exposure. Here, the Rac peptide suppressed lamellipodium formation, increased the number of filopodia, abolished cathodal filopodial orientation, and prevented cathodal steering. The Cdc42 peptide suppressed filopodium formation, increased lamellipodial area and prevented cathodal steering. The cathodal bias of lamellipodia was independent of Cdc42 CRIB activity and was not sufficient for cathodal steering in the absence of filopodia, but the cathodal bias of filopodia through Rac CRIB activity was necessary for cathodal turning. Understanding the mechanism for cathodal growth cone guidance will enhance the emerging clinical effort to stimulate human spinal cord regeneration through EF application.
Direct current treatment (DCT) is a treatment for malignant tumors suggested by Nordenström in 1978. In DCT, two platinum electrodes, an anode and a cathode, are introduced percutaneously. Usually the anode is inserted into the tumor, and the cathode is inserted into healthy tissue near the tumor. Passage of a direct current acidifies the surroundings of the anode and causes necrosis of this part of the tumor. DCT has been used to treat lung cancer and superficial tumors clinically, but it has not yet been used for intra-abdominal tumors. Here, basic and experimental studies were made of the possibility of DCT of intra-abdominal tumors. A modification, called transvascular DCT, was done with the anode inserted into the liver of rabbits and the cathode placed within a blood vessel by vascular catheterization. First, tests were done to identify a suitable material for the cathode, from the standpoint of safety. DCT is usually done with platinum electrodes. However, in transvascular DCT, platinum could not be used for the cathode because with its use, hydrogen gas was produced in the vessel, causing embolisms. So, a cathode made of AgCl and coated with Ag was developed to prevent embolism. With this cathode, gas was not generated. Next, pathological changes in the walls of the vessel that contained the cathode were observed after DCT. The cathode was put into a tube placed in the inferior vena cava (IVC) or the aorta. a. IVC: A histological study done immediately after DCT showed an area of necrosis in the wall of the IVC in all 19 rabbits. A study done 7 days after DCT showed damage in the IVC wall of all five animals examined. b. Aorta: A histological study done immediately after DCT showed a small edematous area in the wall of the aorta in seven of the 22 animals, and no evidence of any damage in the other 15. A study done 7 days after DCT showed no damage in any of the 16 animals. The aorta was more suitable for use as the vessel to contain the cathode than the IVC, because injury of its wall was minor and reversible. Thus, transvascular DCT could be done safely by use of an Ag-coated cathode made of AgCl and placed in the aorta.
The pH transients that occur during isoelectric trapping separations as a result of the removal of nonampholytic ionic components have been re-examined. Salts containing strong electrolyte anions and cations, both with equal and dissimilar mobilities, have been studied using anodic and cathodic buffering membranes whose pH values were both equidistant and nonequidistant from pH 7. The direction and magnitude of the pH transient (acidic or basic) was found to depend on both the mobilities of the anion and cation (mu(anion)/mu(cation)) and the pH difference between pH 7 and the pH of the buffering membranes (|pH(memb) (anodic) - 7|/|7 - pH(memb) (cathodic)|). When |pH(memb) (anodic) - 7|/|7 - pH(memb) (cathodic)| = 1, mu(anion)/mu(cation)<1 leads to an acidic pH transient, mu(anion)/mu(cation) = 1 eliminates the pH transient and mu(anion)/mu(cation)>1 leads to a basic pH transient. When mu(anion)/mu(cation) = 1, |pH(memb) (anodic) - 7|/|7 - pH(memb) (cathodic)|<1 leads to a basic pH transient, |pH(memb) (anodic) - 7|/|7 - pH(memb) (cathodic)| = 1 eliminates the pH transient and |pH(memb) (anodic) - 7|/|7 - pH(memb) (cathodic)|>1 leads to an acidic pH transient. By selecting appropriate anodic and cathodic buffering membranes to adjust the |pH(memb) (anodic) - 7|/|7 - pH(memb) (cathodic)| value, pH transients caused by dissimilar anion and cation mobilities can be avoided.
Wounding corneal epithelium establishes a laterally oriented, DC electric field (EF). Corneal epithelial cells (CECs) cultured in similar physiological EFs migrate cathodally, but this requires serum growth factors. Migration depends also on the substrate. On fibronectin (FN) or laminin (LAM) substrates in EF, cells migrated faster and more directly cathodally. This also was serum dependent. Epidermal growth factor (EGF) restored cathodal-directed migration in serum-free medium. Therefore, the hypothesis that EGF is a serum constituent underlying both field-directed migration and enhanced migration on ECM molecules was tested. We used immunofluorescence, flow cytometry, and confocal microscopy and report that 1) EF exposure up-regulated the EGF receptor (EGFR); so also did growing cells on substrates of FN or LAM; and 2) EGFRs and actin accumulated in the cathodal-directed half of CECs, within 10 min in EF. The cathodal asymmetry of EGFR and actin staining was correlated, being most marked at the cell-substrate interface and showing similar patterns of asymmetry at various levels through a cell. At the cell-substrate interface, EGFRs and actin frequently colocalized as interdigitated, punctate spots resembling tank tracks. Cathodal accumulation of EGFR and actin did not occur in the absence of serum but were restored by adding ligand to serum-free medium. Inhibition of MAPK, one second messenger engaged by EGF, significantly reduced EF-directed cell migration. Transforming growth factor beta and fibroblast growth factor also restored cathodal-directed cell migration in serum-free medium. However, longer EF exposure was needed to show clear asymmetric distribution of the receptors for transforming growth factor beta and fibroblast growth factor. We propose that up-regulated expression and redistribution of EGFRs underlie cathodal-directed migration of CECs and directed migration induced by EF on FN and LAM.
Materials fatigue and gross biocompatability of an implantable bone growth stimulator (BGS) were assessed in a 6-month trial using 6 ponies. The forelegs of each pony were implanted with a BGS; the right leg implant had the cathode and cathode lead preconnected by the manufacturer, and the left leg implant was connected at surgery. Evaluation was by radiographic and clinical examination at the beginning and end of the experimental period. Six of the 12 cathode leads (50%) and 7 of the 12 cathodes (58%) were broken at 6 months. All of the implanted preconnected cathode and insulated cathode leads and 33.3% of the surgically connected cathodes and insulated cathode leads were connected at the titanium connector socket at 6 months. This BGS may exhibit wire fatigue greater than 50% of the time when used in the distal extremity of the horse.