Changes In Tissue Resistance Research Articles

Change in tissue resistance after irreversible electroporation in liver tumors as an indicator of treatment success - A multi-center analysis with long term follow-up

IntroductionA nationwide multicenter study was performed to examine whether there is a correlation between decrease in tissue resistance and time to local tumor recurrence after irreversible electroporation (IRE) in patients with hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRCLM). MethodsAll patients treated with IRE for liver tumors in Sweden from 2011 until 2018 were included. Patient characteristics and recurrence patterns were obtained from medical records and radiological imaging. All procedural data from the IRE hardware at the three hospitals performing IRE were retrieved. The resistance during each pulse and the change during each treatment were calculated. The electrode pair with the smallest decrease in tissue resistance was used and compared with the time to LTP. Results149 patients with 206 tumors were treated. Exclusion due to missing and inaccurate data resulted in 124 patients with 170 tumors for the analyses. In a multivariable Cox regression model, a smaller decrease in tissue resistance and larger tumor size were associated with shorter time to local tumor recurrence for CRCLM, but not for HCC. ConclusionThere was an association between a decrease in tissue resistance and time to local tumor recurrence for CRCLM. The decrease in resistance, in combination with a rise in current, may be the parameters the interventionist should use during IRE to decide if the treatment is successful.

Tissue Resistance Decrease during Irreversible Electroporation of Pancreatic Cancer as a Biomarker for the Adaptive Immune Response and Survival

PurposeTo correlate irreversible electroporation (IRE) procedural resistance changes with survival outcomes and the IRE-induced systemic immune response in patients with locally advanced pancreatic cancer (LAPC). Materials and MethodsData on IRE procedural tissue resistance (R) features and survival outcomes were collected from patients with LAPC treated within the context of 2 prospective clinical trials in a single tertiary center. Preprocedural and postprocedural peripheral blood samples were prospectively collected for immune monitoring. The change (ie, decrease) in R during the first 10 test pulses (ΔR10p) and during the total procedure (ΔRtotal) were calculated. Patients were divided in 2 groups on the basis of the median change in R (large ΔR vs small ΔR) and compared for differences in overall survival (OS) and progression-free survival and immune cell subsets. ResultsA total of 54 patients were included; of these, 20 underwent immune monitoring. Linear regression modeling showed that the first 10 test pulses reflected the change in tissue resistance during the total procedure appropriately (P < .001; R2 = 0.91). A large change in tissue resistance significantly correlated with a better OS (P = .026) and longer time to disease progression (P = .045). Furthermore, a large change in tissue resistance was associated with CD8+ T cell activation through significant upregulation of Ki-67+ (P = .02) and PD-1+ (P = .047). Additionally, this subgroup demonstrated significantly increased expression of CD80 on conventional dendritic cells (cDC1; P = .027) and PD-L1 on immunosuppressive myeloid-derived suppressor cells (P = .039). ConclusionsIRE procedural resistance changes may serve as a biomarker for survival and IRE-induced systemic CD8+ T cell and cDC1 activation.

Change in Tissue Resistance during Irreversible Electroporation of Liver Tumors as an Indicator of Treatment Success: A Multicenter Analysis with Long-term Follow-up

Change in Tissue Resistance during Irreversible Electroporation of Liver Tumors as an Indicator of Treatment Success: A Multicenter Analysis with Long-term Follow-up

Uniaxial strain of cultured mouse and rat cardiomyocyte strands slows conduction more when its axis is parallel to impulse propagation than when it is perpendicular.

Cardiac tissue deformation can modify tissue resistance, membrane capacitance and ion currents and hence cause arrhythmogenic slow conduction. Our aim was to investigate whether uniaxial strain causes different changes in conduction velocity (θ) when the principal strain axis is parallel vs perpendicular to impulse propagation. Cardiomyocyte strands were cultured on stretchable custom microelectrode arrays, and θ was determined during steady-state pacing. Uniaxial strain (5%) with principal axis parallel (orthodromic) or perpendicular (paradromic) to propagation was applied for 1minute and controlled by imaging a grid of markers. The results were analysed in terms of cable theory. Both types of strain induced immediate changes of θ upon application and release. In material coordinates, orthodromic strain decreased θ significantly more (P<.001) than paradromic strain (2.2±0.5% vs 1.0±0.2% in n=8 mouse cardiomyocyte cultures, 2.3±0.4% vs 0.9±0.5% in n=4 rat cardiomyocyte cultures, respectively). The larger effect of orthodromic strain can be explained by the increase in axial myoplasmic resistance, which is not altered by paradromic strain. Thus, changes in tissue resistance substantially contributed to the changes of θ during strain, in addition to other influences (eg stretch-activated channels). Besides these immediate effects, the application of strain also consistently initiated a slow progressive decrease in θ and a slow recovery of θ upon release. Changes in cardiac conduction velocity caused by acute stretch do not only depend on the magnitude of strain but also on its orientation relative to impulse propagation. This dependence is due to different effects on tissue resistance.

Irreversible electroporation of stage 3 locally advanced pancreatic cancer: optimal technique and outcomes.

Irreversible electroporation (IRE) of stage 3 pancreatic adenocarcinoma has been used to provide quality of life time in patients who have undergone appropriate induction therapy. The optimal technique has been reported within the literature, but not in video form. IRE of locally advanced pancreatic cancer is technically demanding requiring precision ultrasound use for continuous imaging in multiple needle placements and during IRE energy delivery. Appropriate patients with locally advanced pancreatic cancer should have undergone appropriate induction chemotherapy for a reasonable duration. The safe and effective technique for irreversible electroporation is preformed through an open approach with the emphasis on intra-operative ultrasound and intra-operative electroporation management. The technique of open irreversible electroporation of the pancreas involves bracketing the target tumor with IRE probes and any and all invaded vital structures including the celiac axis, superior mesenteric artery (SMA), superior mesenteric-portal vein, and bile duct with continuous intraoperative ultrasound imaging through a caudal to cranial approach. Optimal IRE delivery requires a change in amperage of at least 12 amps from baseline tissue conductivity in order to achieve technical success. Multiple pull-backs are necessary since the IRE ablation probe lengths are 1 cm and thus needed to achieve technical success along the caudal to cranial plane. Irreversible electroporation in combination with multi-modality therapy for locally advanced pancreatic carcinoma is feasible for appropriate patients with locally advanced cancer. Technical demands are high and require the highest quality ultrasound for precise spacing measurements and optimal delivery to ensure adequate change in tissue resistance.

Respiratory impedance model with lumped fractional order diffusion compartment

In this work, a revisited model of the respiratory system is proposed comprising a recurrent ladder network and a lumped fractional order diffusion compartment. Identification is performed on 31 healthy subjects. The data for identification has been gathered using the forced oscillation lung function test, which delivers a non- parametric model of the impedance. The ladder network parameters have been identified and a fractional order has been calculated from the recurrent ratios of the respiratory mechanics (resistance and compliance). The results suggest that the proposed model can characterize the respiratory impedance over a long range of frequencies (5-250Hz). In order to check the validity of the diffusion compartment, an illustrative example has been used to see if the fractional order value of the diffusion compartment is sensitive to changes in tissue resistance. The results support the conclusion that this is a reliable parameter to capture the changes in the distal airways.

Progesterone Modulates Integrin α2 (ITGA2) and α11 (ITGA11) in the Pregnant Cervix

Fibrillar collagen in the cervical extracellular matrix (ECM) is the predominant component providing mechanical support. Cellular integrins contribute to structural integrity by cross-linking ECM components. We investigated the expression of collagen-binding integrins in the normal rat gestation and after treatment with mifepristone to determine whether integrin modulation is involved in changes in tissue resistance. Cervical tissue was harvested from nonpregnant and timed pregnant Sprague-Dawley rats. Normal gestational expression was evaluated in nonpregnant and timed pregnant tissue on days 12, 16, 18, 20, 21 and 22. Progesterone inhibition was induced with 3 mg mifepristone administered on day 15. Primary rat cervical stromal (RCS) cell cultures were generated from nonpregnant rats using tissue explants. The effects of progesterone environment on RCS cells were evaluated in the presence and absence of various inhibitors. Protein expression and signaling pathways were evaluated by Western blot. Integrin α2 (ITGA2) expression increased over gestation, peaking at the end of gestation (analysis of variance [ANOVA] P < .01). Integrin α11 (ITGA11) expression increased through mid-gestation, peaking on day 18 and decreasing through day 22 (ANOVA P < .001). Progesterone increased the expression of ITGA11 and phosphorylated focal adhesion kinase ([pFAK] P < .002). Mifepristone blocked these effects in vitro. Mifepristone increased ITGA2 and phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2) in vivo and in vitro. Mifepristone-induced upregulation of ITGA2 was abrogated by inhibition of ERK1/2. Progesterone/progesterone withdrawal is involved in regulating the expression of collagen-binding integrins. These changes differ among the collagen-binding integrins. Mitogen-activated protein kinase (MAPK) signaling is involved in regulating some of these integrins.

Acute Effects of Bile Acids on the Pancreatic Duct Epitheliumin Vitro

Background.Acute pancreatitis is associated with passage of gallstones, although the mechanism(s) linking the two processes remains undefined. Bile reflux into the pancreatic duct could play a role but the experimental conditions often employed to induce pancreatitis rarely develop clinically. Here we examined whether low concentrations of bile affect ductal electrophysiology as an indirect measure of ductal epithelial integrity and functionin vitro.Methods.The main duct was dissected out of freshly harvested bovine pancreata, cut into 1- × 2-cm sections, placed in tissue culture for 48–72 h, then placed in Ussing chambers. Changes in tissue resistance (Rt) and short-circuit current (Isc) were monitored. The responses to forskolin and bile (taurodeoxycholic acid, TDCA) were examined separately and together.Results.Forskolin (10 μM) produced a decrease in theIscwithout a significant change inRt, suggesting a secretory response, followed by a return to baseline. TDCA caused a similarly reversible decrease in theIscat low doses, but a persistent drop at higher concentrations. A concurrent drop inRtwas noted at all TDCA concentrations, the duration of which correlated with dosage and degree of histological damage. Prior exposure to low (0.5 mM) doses of TDCA significantly blunted the response to subsequent forskolin challenge.Conclusions.Acute exposure to TDCAin vitrocauses epithelial damage at levels lower than those normally used to induce experimental pancreatitis. At the lower concentrations,Rtreturns to baseline rapidly, suggesting recovery (restitution) from epithelial damage but with a persistent loss of the response to forskolin. Reflux of minute amounts of bile into the pancreatic duct could play a significant role in the pathogenesis of gallstone pancreatitis by uncoupling the normal stimulus-secretion apparatus of the ductal system and breaking down the epithelial barrier.

Greater airway narrowing in immature than in mature rabbits during methacholine challenge.

It has been demonstrated that methacholine (MCh) challenge produces a greater increase in lung resistance in immature than in mature rabbits (R. S. Tepper, X. Shen, E. Bakan, and S. J. Gunst. J. Appl. Physiol. 79: 1190-1198, 1995). To determine whether this maturational difference in the response to MCh was primarily related to changes in airway resistance (Raw) or changes in tissue resistance, we assessed airway narrowing in 1-, 2-, and 6-mo-old rabbits during intravenous MCh challenge (0.01-5.0 mg/kg). Airway narrowing was determined from measurements of Raw in vivo and from morphometric measurements on lung sections obtained after rapidly freezing the lung after the MCh challenge. The fold increase in Raw was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. Similarly, the degree of airway narrowing assessed morphometrically was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. The fold increase in Raw was highly correlated with the degree of airway narrowing assessed morphometrically (r2 = 0.82, P < 0.001). We conclude that the maturational difference in the effect of MCh on lung resistance is primarily caused by greater airway narrowing in the immature rabbits.

Protein kinase C regulates prairie dog gallbladder ion transport.

Gallstone formation is characterized by increased biliary calcium (Ca2+) level and altered gallbladder absorption. Recent studies suggest that luminal Ca2+ regulates gallbladder ion transport via intracellular calcium ([Ca2+]ic). Ca2+-calmodulin and protein kinase C (PKC) are two major systems through which [Ca2+]ic carries out second-messenger functions in many cell types. We have previously shown that Ca2+-calmodulin regulates basal gallbladder ion transport in prairie dog. The present study tests the hypothesis that PKC is also essential in regulation of gallbladder ion transport in this model. The role of PKC in regulation of gallbladder ion transport was determined by studying the effects of phorbol esters, synthetic analogues of diacylglycerol, which directly activates PKC. Gallbladders were mounted in Ussing chambers, and standard electrophysiologic parameters were recorded after exposing tissues to either 10(-5) mol/L of 4-alpha-phorbol 12,13-didecanoate (PDD), 4-beta-phorbol 12-myristate 13-acetate, 4-beta-phorbol 12,13-dibutyrate (PDB), or 10(-4) mol/L serotonin. Unidirectional Na+, Cl-, and H2O fluxes were measured before and after treatment with only inactive PDD and most active PDB. Mucosal and serosal exposure of tissues to either 4-beta-phorbol 12-myristate 13-acetate or PDB resulted in a decrease in short-circuit current and transepithelial potential difference without any change in tissue resistance. Serotonin induced similar changes in gallbladder electrical properties. PDB caused an inhibition of mucosal to serosal fluxes of Na+, Cl-, and H2O, with a decrease in net Na+ absorption, an increase in net Cl- secretion, and a conversion of net H2O absorption to net H2O secretion. Serosal-to-mucosal fluxes of Na+, Cl-, and H2O did not change. Inactive PDD had no effect on either electrophysiologic parameters or ion and water fluxes. Pretreatment of tissues with PKC antagonist 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine blocked the phorbol ester-induced inhibition of ion transport. PKC regulates gallbladder ion transport in the prairie dog by inhibiting Na+ absorption and stimulating Cl- secretion.

Ripening of Nectarine Fruit (Changes in the Cell Wall, Vacuole, and Membranes Detected Using Electrical Impedance Measurements).

Electrical impedance measurements were used to characterize changes in intracellular and extracellular resistance as well as changes in the condition of membranes during ripening of nectarines (Prunus persica [L.] Batsch cv Fantasia). These measurements were related to changes in fruit texture assessed by flesh firmness and apparent juice content. An electrical model indicated that, during ripening (d 1-5) of freshly harvested fruit, the resistance of the cell wall and vacuole declined by 60 and 26%, respectively, and the capacitance of the membranes decreased by 9%. Accurate modeling of the impedance data required an additional resistance component. This resistance, which declined by 63% during ripening, was thought to be associated with either the cytoplasmic or membrane resistance. Changes in tissue resistance measured using low frequencies of alternating current were closely related to flesh firmness. After storage at 0[deg]C for 8 weeks, the nectarines developed a woolly (dry) texture during ripening at 20[deg]C. The main difference between these chilling-injured nectarines and fruit ripened immediately after harvest was the resistance of the cell wall, which was higher in woolly tissue (4435 [omega] after 5 d at 20[deg]C) than in nonwoolly tissue (2911 [omega] after 5 d at 20[deg]C). The results are discussed in relation to physiological changes that occur during the ripening and development of chilling injury in nectarine fruit.

Electrical impedance studies of nectarines during coolstorage and fruit ripening

The electrical impedance of ripe and unripe nectarine fruit was measured at harvest and after 3 and 8 weeks storage at 0°C, using frequencies of alternating current between 50 Hz and 0.1 MHz. The complex impedance was separated into its resistive and reactive components for both the electrodes and the fruit flesh. Electrode impedance was higher in stainless steel than in silver electrodes, and stainless steel electrodes were influenced by changes in ionic conditions. The resistance of whole fruit was lower than that of excised blocks of tissue from the same fruit. Changes in tissue resistance were greatest at low frequencies (50–100 Hz), with resistance increasing between 0 and 3 weeks storage and decreasing between 3 and 8 weeks storage. Changes in electrical resistance of nectarines are discussed, with the assumption that low frequency current travels via an extracellular pathway, and high frequency current travels via an intracellular pathway.

Effect of lung volume on plateau response of airways and tissue to methacholine in dogs.

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoil.

Potassium channel blockers inhibit anion secretion in cultured rat epididymal epithelium.

The effect of putative K channel blockers on anion secretion has been studied in primary monolayer cultures of rat epididymal cells using the short circuit current technique. Under basal conditions, monolayers had a transepithelial potential difference of about 2-3 mV, apical side negative and a short circuit current (SCC) of about 2 microA.cm-2. The transepithelial resistance was about 500 omega.cm2. Addition of adrenaline (0.23 microM, basolaterally) caused the SCC to rise to a peak value of about 10.5 microA.cm-2 and then stabilized at about 4 microA.cm-2 after 15 min. This rise in the short circuit current has previously been shown to be due to an increase in net anion secretion from the basolateral to the apical medium. In tissues stimulated with adrenaline, addition of barium (Ba) to the apical side did not affect the adrenaline-induced SCC, but addition to the basolateral side caused a dose-dependent inhibition of the current with an IC50 value (concentration required to inhibit 50% of the current) of 0.92 mM. At Ba concentration of 5 mM, the adrenaline-induced SCC was completely abolished. There was no effect on transepithelial resistance. Addition of tetraethylamonium (TEA) (16 mM) to the apical or basolateral side had no significant effect on the adrenaline-stimulated SCC. Lidocaine and quinidine inhibited the adrenaline-stimulated SCC when added either to the apical or basolateral bathing solution. The IC50 values for lidocaine were 0.42 mM and 0.35 mM for basolateral and apical application, respectively. The IC50 values for quinidine were 0.062 mM and 0.050 mM for basolateral and apical application, respectively. In all cases there was no change in tissue resistance. It is proposed that in the basolateral membrane of the epididymal cells, there is a component which is sensitive to putative K channel blockers. It is likely that it is a K channel. As in other secretory cells, this channel plays an important role in secretion.

Origin of the light peak: in vitro study of Gekko gekko.

1. The light peak is a large, light-evoked increase in standing potential recorded in mammals, birds and reptiles. We have studied the cellular origin of the light peak in an in vitro preparation of neural retina-pigment epithelium (r.p.e)-choroid from the lizard, Gekko gekko. The tissue was mounted between two separate bathing solutions; the trans-tissue potential was recorded retinal-side positive; micro-electrodes were introduced to measure the trans-epithelial potential (t.e.p.) and to record intracellularly from the r.p.e.2. A 10 min stimulus of diffuse white light evoked an increase in trans-tissue potential that reached maximum amplitude, the light peak, about 15 min after stimulus onset. Since the light peak is present in vitro, it must originate in either the neural retina or the r.p.e.3. A micro-electrode was positioned in the subretinal space and the trans-retinal potential and t.e.p. were measured simultaneously. A 10 min stimulus produced an increase in t.e.p. equal in magnitude and time course to the trans-tissue light peak; no potential was present across the retina. The light peak is therefore generated solely across the r.p.e.4. Intracellular r.p.e. recordings were made to determine whether the light peak was generated at the apical or basal membrane or across the paracellular shunt. A 10 min stimulus first caused a hyperpolarization of both membranes with a time course similar to the r.p.e. c-wave followed by a depolarization of both membranes with the time course of the light peak. We conclude that whereas the r.p.e. c-wave results from a hyperpolarization of the apical membrane, the light peak is generated by a depolarization of the basal membrane of the r.p.e.5. Changes in tissue resistance, R(t), and the ratio of apical to basal membrane resistances, a, were monitored during the light peak by passing current across the tissue and measuring the appropriate current-induced voltages. R(t) decreased and a increased with the time course of the light peak. Assuming that the paracellular shunt resistance is constant, we conclude that the light peak is accompanied by an increase in basal membrane conductance.6. This and the following paper present the first direct demonstration of an interaction between the neural retina and the basal membrane of the r.p.e. The light peak, initiated by absorption of light by photoreceptors, results in a depolarization and conductance increase of the basal membrane.

The effect of acetylcholine on the electrical activity of intestinal epithelial cells

1. 1. The effect of the neurohumoral transmitter, acetylcholine, on the transepithelial electrical activity of rat jejunum was investigated both in vitro and in vivo. 2. 2. Acetylcholine caused an increase in the transintestinal potential difference and this change was related to log dose, a sigmoid curve being obtained. 3. 3. The increased potential difference reflected an alteration in net ion transport since no significant change in tissue resistance was observed. 4. 4. The effect of acetylcholine was antagonised by atropine and enhanced by neostigmine, suggesting that acetylcholine is acting through the type of receptor usually associated with postjunctional cholinergic effector cells. 5. 5. These observations suggest the possibility that intestinal transport activity may be under the control of the autonomic nervous system.