Cardiac responses to shock in curarized dogs: effects of shock intensity and duration, warning signal, and prior experience with shock.
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The IbpA and IbpB are 16-kDa Escherichia coli proteins belonging to a family of small heat-shock proteins (sHsps). According to the present model, based on the in vitro experiments, sHsps are molecular chaperones that bind and prevent aggregation of nonnative proteins during heat shock. Previously, we have shown that IbpA and IbpB bind to endogenous E. coli proteins aggregated intracellularly by heat shock, which can be separated from soluble proteins and membranes in sucrose density gradients (fraction S). In this work we have found that marine bacterium Vibrio harveyi contains a single sHsp which is strongly induced by heat shock and reacts with the anti-IbpA/B serum. The 26 amino-terminal amino acids of this sHsp bear high homology to E. coli IbpA and IbpB proteins (73% and 54% identity, respectively). Fraction S was prepared from heat-shocked cells of V. harveyi, it contained high amounts of the IbpA/B protein. This result indicates that the IbpA/B protein of V. harveyi binds to the proteins that aggregate in V. harveyi cells during heat shock.
In a series of experiments, the effect of parachlorophenylalanine (PCPA) on shock-induced fighting was assessed rats raised and maintained under either a 12-hr alternating light-dark cycle (LD) or constant light conditions (LL). PCPA increased shock-induced aggression only in LL groups when testing was accomplished using a 2 mA shock; PCPA resulted in increased aggression in groups from the LD condition only when testing was done at 1 mA. A procedure that used castrated and intact cagemates to manipulate home-cage social experience provided evidence for a role for social experience in determining differences between LL and LD reared rats in shock-induced aggression. However, these data also suggested that home-cage social experience was not a factor in the lighting condition influence on the effect of PCPA on shock-induced aggression. Finally, a separate experiment demonstrated that diurnal rhythms in shock-induced aggression were disrupted by handling and vehicle injection in the control procedures, so the possible role of serotonin in diurnal rhythms of aggression behavior could not be assessed.
The present experiment was designed to study whether or not prior exposure to inescapable shock is accompanied by sex-dependent changes in pituitary and central levels of immunoreactive beta-endorphin, which is proposed to play an important role in opioid analgesia induced by aversive stimulation. Further, the effects of brief reexposure (5 min) to the chamber where inescapable shock was experienced earlier, were established in both sexes. Elevated levels of beta-endorphin were found 24 hours after inescapable shock, in the anterior pituitary of males and in the midbrain periaqueductal gray of both males and females. Reexposure to the experimental chamber only affected beta-endorphin levels if shock had been experienced in this chamber. Reexposure after inescapable shock reduced beta-endorphin content of the arcuate nucleus of males and beta-endorphin content of the periaqueductal gray of males and females. The present results are related to previous findings of sensitization and conditioning of analgesic reactions. The sex differences found in the present experiment are discussed with respect to sex-dependent behavioral consequences of inescapable shock.
Wistar rats were sensitized for anaphylactic shock with ovalbumin and treated intraperitoneally with 10 injections of methionine-enkephalin and leucine-enkephalin (4 mg/kg of body weight). Both pentapeptides suppressed the development of systemic anaphylaxis after intravenous injection of a shocking dose of ovalbumin. Methionine-enkephalin completely protected the animals from fatal shock. The level of circulating IgE and precipitating anti-ovalbumin antibodies decreased in rats given 10 injections of enkephalins. Mast cell degranulation was significantly inhibited in these animals as observed at autopsy. A single intraperitoneal injection of 4 mg/kg body weight of methionine-enkephalin given 30 min before the challenge with shock-inducing dose of antigen was also effective, although to a lesser extent, in protecting animals from anaphylactic shock. One injection of leucine-enkephalin did not exhibit significant antishock activity. The results suggest that enkephalins, and methionine-enkephalin in particular, are potent modulators of the complex biochemical processes underlying the anaphylactic shock in the rat.
Memory disruption by posttraining electroconvulsive shock was studied in adult Wistar rats using three different tasks: step-down inhibitory avoidance, two-way active avoidance, and habituation of rearing to an open field. The animals were given training and test sessions 24 hours apart in each of these tasks. Immediate posttraining transcorneal, 15 mA, 60 Hz, 2 sec electroconvulsive shock disrupted memory of the three tasks. The effect was completely reversed by the IP administration of beta-endorphin (2.0 micrograms/kg), 6 min prior to testing, or of another electroconvulsive shock, 30 min prior to testing. These findings indicate that the posttraining electroconvulsive shock did not affect memory storage. In view of the fact that electroconvulsive shock has been previously shown to cause a pronounced decrease of brain beta-endorphin immunoreactivity, attributable to a release of the peptide, the present findings can be interpreted as showing that memory disruption by posttraining electroconvulsive shock results from the induction of state dependency on beta-endorphin.
Biphasic shocks are more effective than damped sine wave monophasic shocks for transthoracic cardioversion (CV) of atrial fibrillation (AF), but the optimal protocol for CV with biphasic shocks has not been defined. We conducted a prospective, randomized study of 120 consecutive patients with persistent AF to delineate the dose-response curve for CV of AF with a biphasic truncated exponential shock waveform and to identify clinical predictors of shock efficacy. Our data suggest that the initial shock energy for CV with this waveform should be 200 J if the patient weighs <90 kg and 360 J if the patient weighs >/=90 kg.
In a sample of 208 Holtzman-descended albino rats, we found evidence with 4 measures of conditioning (freezing, defecation, side crossing, and nose crossing) that a single 2-s, 1.0-mA immediate shock could condition fear to a context (Experiments 1, 2, and 4). When we reduced the shock intensity to 0.5 mA, we obtained a complete immediate-shock conditioning deficit according to all measures in Experiment 3 and to all but the defecation measure in Experiment 4. Results suggest two conclusions: (a) Differences in shock potency between laboratories may help explain discrepant findings about whether immediate shock supports contextual conditioning; (b) theories of contextual conditioning need a mechanism that permits that conditioning to result from immediate shock.
The effects of cooling on associative learning and memory processes in Caenorhabditis elegans were investigated by giving the worms cold shock at various times before or after conditioning. A pretraining cold shock in the 30 min immediately before conditioning and a posttraining cold shock in the 30 min immediately after conditioning both disrupted learning and memory processes tested a short time after conditioning. However, if tested 3 hr after conditioning, worms given a pretraining cold shock demonstrated learned preferences, whereas worms given a posttraining cold shock still had memory deficits. These results suggest that the effects of cold shock on associative learning and memory can be dissociated into effects on memory retrieval and memory retention.
BACKGROUND: Psychological distress is both a precipitant and a consequence of ICD shock. Therefore, the assessment of patient anxiety and concerns related to receiving an ICD shock may prompt appropriate psychological referrals and treatment. METHODS: The purpose of this study is to assess the initial validity and clinical utility of the Florida Shock Anxiety Scale (FSAS). Seventy-two ICD recipients completed the FSAS. RESULTS: Exploratory factor analysis revealed a two-factor structure with items loading such that Factor 1 could be conceptualized as a Consequence Factor (e.g., fearing creating a scene if the device were to fire) and Factor 2 as a Trigger Factor (e.g., fearing sexual activity). Alpha coefficients suggest good reliability (Cronbach's alpha= 0.91, split-half = 0.92), and FSAS Total Score was moderately correlated (r =-0.65) with total score on the Multidimensional Fear of Death Scale. CONCLUSIONS: Two subscales, labeled consequence of shock and trigger of shock, were established via factor analysis. Collectively the FSAS demonstrates potential utility to assess shock distress and warrants additional investigation.
Experimental studies have shown that the magnitude of the shock-induced transmembrane potential (Vm) saturates with increasing electric field strength. This study uses a mathematical model to investigate the effects of electroporation and membrane kinetics on Vm in a cardiac fiber. The model consists of the core conductor equation for a one-dimensional fiber, where excitability is represented by the Luo-Rudy dynamic model (1994-1995) and electroporation is described by a membrane conductance that increases exponentially with Vm squared. For shocks delivered during the plateau of an action potential, the model reproduces the experimentally observed saturation of Vm with a root mean square error of 4.27% and a correlation coefficient of 0.9992. For shocks delivered during diastole, the saturation of Vm is qualitatively reproduced even when the sodium and calcium channels are inactivated. Quantitative replication of the response to diastolic shocks is hindered by the choice of electroporation parameters (optimized for shocks delivered during the plateau) and differences in the membrane kinetics between model and experiment. The complex behavior of Vm during large shocks is due to a combination of electroporation, electrotonus, propagation, and active membrane kinetics. The modeling results imply that the experimentally observed saturation of Vm is due to electroporation of the lipid bilayer.
A homolog of the major eubacterial cold shock gene cspA was identified in Sinorhizobium meliloti RM1021 by luxAB reporter transposon mutagenesis. Here we further characterize the organization and regulation of this locus. DNA sequence analysis indicated that the locus includes three open reading frames (ORFs) encoding homologs corresponding to CspA, a novel 10.6-kDa polypeptide designated ORF2, and a homolog of the Escherichia coli ribosomal protein S21. Transcription analysis indicated that this locus produced two different-sized cspA-hybridizing transcripts upon cold shock, a 400-nucleotide (nt) RNA encoding cspA alone and a 1, 000-nt transcript encoding cspA-ORF2-rpsU. The sizes of the transcripts agreed with the location of the transcription start site determined by primer extension and the locations of two putative transcriptional terminators. The promoter of the cspA-ORF2-rpsU locus had -10 and -35 elements similar to the E. coli sigma(70) consensus promoter and, like the cspA locus of E. coli, included an AT-rich region upstream of the -35 hexamer. The promoter of the S. meliloti cspA locus was found to impart cold shock-induced mRNA accumulation. In addition, the 5'-untranslated region (5' UTR) was found to increase the fold induction of cspA transcripts after cold shock and depressed the level of luxAB mRNA prior to cold shock, another feature similar to cspA regulation in E. coli. No "cold box" was identified upstream of the S. meliloti cspA gene, however, and there was no other obvious sequence identity between the S. meliloti 5' UTR and that of E. coli. DNA hybridization analysis indicated that outside the cspA-ORF2-rpsU cold shock locus there are several additional cspA-like genes and a second rpsU homolog.
Toxic shock toxin (TST), also known as pyrogenic exotoxin C (Schlievert et al., J. Infect. Dis. 143:509-516, 1981) and staphylococcal enterotoxin F (Bergdoll et al., Lancet i:1017-1021, 1981), was purified from toxic shock strains of Staphylococcus aureus by preparative isoelectric focusing and by chromatofocusing. Neither method produced an absolutely pure protein as determined by silver staining of sodium dodecyl sulfate-acrylamide gels, although chromatofocusing was the better method of the two. Three molecular weight variants of the protein were found in the two toxic shock syndrome strains that were studied, regardless of the purification method that was used. An isoelectric point of 7.15 and molecular weights of 21,400, 22,100, and 23,200 were determined for the different forms of the protein from electrophoresis data. A sedimentation coefficient of 2.3S was determined by sucrose gradient centrifugation, and a Stokes radius of 2 X 10(-7) cm was determined by gel filtration. An average molecular weight of 18,900 for all of the TST forms was calculated from these data by the Stokes-Einstein equation. A survey for TST in 32 control and 46 toxic shock strains of S. aureus by isoelectric focusing and by agarose gel double immunodiffusion with specific rabbit antiserum revealed that the isoelectric focusing method tends to overestimate the number of TST-positive strains because of the detection of non-TST, neutral staphylococcal proteins. Based on immunodiffusion data, the association of TST with toxic shock strains was found to be 100% in vaginal isolates and 62% in non-vaginal isolates. In the control strains, TST was found in 16% of the vaginal strains and 23% of the non-vaginal strains. The value of this toxin as a marker for toxic shock and its relationship to the pathogenesis of this disease are discussed.
This study presents a global transcriptional analysis of the cold shock response of Shewanella oneidensis MR-1 after a temperature downshift from 30 degrees C to 8 or 15 degrees C based on time series microarray experiments. More than 700 genes were found to be significantly affected (P < or = 0.05) upon cold shock challenge, especially at 8 degrees C. The temporal gene expression patterns of the classical cold shock genes varied, and only some of them, most notably so1648 and so2787, were differentially regulated in response to a temperature downshift. The global response of S. oneidensis to cold shock was also characterized by the up-regulation of genes encoding membrane proteins, DNA metabolism and translation apparatus components, metabolic proteins, regulatory proteins, and hypothetical proteins. Most of the metabolic proteins affected are involved in catalytic processes that generate NADH or NADPH. Mutational analyses confirmed that the small cold shock proteins, So1648 and So2787, are involved in the cold shock response of S. oneidensis. The analyses also indicated that So1648 may function only at very low temperatures.
The leakage of electrical current to the body surface during defibrillation shock delivery by an implantable cardioverter-defibrillator (ICD) device (the Medtronic Jewel Plus PCD system) was evaluated in 5 dogs. The defibrillation shocks were delivered between the active-can implanted in the left subclavicular region and the endocardial lead placed in the right ventricle at the energy levels of 1, 2, 8, 12, 24 and 34 J. During each delivery, the electrical current leakage from the body surface was measured by electrodes connected to a circuit at 4 recording positions: (A) parallel-subcutaneous (the electrodes were fixed in the subcutaneous tissue of the left shoulder and the right lower chest, and the direction of the electrode vector was parallel to the direction of the defibrillation energy flow); (B) cross-subcutaneous (the electrodes were fixed in the subcutaneous tissue of the right shoulder and the left lower chest, and the vector of the electrodes was roughly perpendicular to the direction of the energy flow); (C) parallel-surface (the electrodes were fixed with ECG paste on the shaved skin surface at the left shoulder and the right lower chest); and (D) surface grounded (the electrodes were fixed on the shaved skin surface at the left shoulder and the left foot, which was grounded). The circuit resistance was set at a variable level (100-5,000 ohms) in accordance with the resistance measured through each canine body. Leakage energies were measured in 750 defibrillation shocks with each circuit resistance in 5 dogs. The leakage energy increased in accordance with the increase of the delivered energy and the decrease of the circuit resistance in all 4 recording positions. When the circuit resistance was set at 1,000 ohms, the leakage energy during shock delivery at 34 J was 32+/-17 mJ at position A, 5+/-9 mJ at B, 10+/-9 mJ at C, and 4+/-3 mJ at D (p=0.042). The peak current was highest at position A and was 87+/-22 mA with a circuit resistance of 1,000 ohms. The power of the leakage energy depended on the delivered energy and the impedance between the electrodes. The angle between the alignment of the recording electrodes and the direction of the energy flow was another important factor in determining the leakage energy. Although the peak current of the leakage energy reached the level of macro shock, the highest leakage energy from the body surface was considerably less because of the short duration of the shock delivery.
Lever pressing by 2 squirrel monkeys was maintained under fixed-interval 6-min and fixed-interval 2-min schedules of electric-shock presentation. Preference for these schedules was assessed during three experimental phases. In all phases, responses on one lever produced shock according to one or the other fixed-interval schedule, and responses on a second, changeover, lever switched between schedules. The opportunity to change over was presented during separate choice periods (during which the fixed-interval schedules did not operate) that followed the first through fourth shocks in each schedule. If no changeover occurred during those choice periods, a changeover automatically occurred following the fifth shock. In Phase I, durations of the choice periods were fixed. In Phase II, the choice periods equaled a proportion of their respective fixed interval. During Phase III (completed with 1 monkey) a response on the changeover lever during a given choice period reinstated the most recent fixed interval, and a failure to respond resulted in a changeover. During each of these phases, distinct preferences developed for the 6-min schedule. These results suggest that the maintenance of lever pressing by fixed-interval presentation of electric shock may not be an example of positive reinforcement, and that the response-maintaining characteristics of shock presentation may derive from other properties of the schedule.
The effects of shock waves in combination with various anti-cancer agents i.e. Bleomycin(BLM), Cis-platinum (CDDP) and 5-fluorouracil(5-FU) on various human cancer cells were examined. It was only with BLM that enhancement was evident in all cell lines. The degree of chemotherapeutic enhancement was proportional to the amount of shock wave energy applied. Ladder formation of DNA in GCIY, a gastric cell line, was observed only when treated with both BLM and shock waves in combination. When SW 480, a colon cancer cell line, transplanted into the back of nude mice were treated with a combination of i.v. injected BLM and regional exposure to shock waves, a significant enhancement of chemotherapeutic effects was observed in terms of the tumor growth curve. When cancer cells exposed to shock waves and observed under scanning and transmission electron microscopes, microvilli on the cell surface disappeared and numerous dimples(diameters distributed from 0.05 to 0.5 microns) became apparent. These dimples were concluded to be pores penetrating through the cell membrane, because reagents such as propidium iodide or 5(6)-carboxyfluorescein could enter cells treated shock waves.