[Free escape & controlled escape; experiences & comments].
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Humans↗
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ECG of the month. Slow bigeminal rhythm. Low atrial or junctional rhythm, second degree atrioventricular block, right ventricular escape beats, ventricular escape-capture bigeminy, ventriculophasic atrial arrhythmia, and right bundle branch block.
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Aged↗
ECG of the month. Benevolent rhythm. Escape impulses; escape rhythm.
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Accelerated Idioventricular Rhythm↗
Changes in escape rhythms several years after radiofrequency ablation of the atrioventricular junction combined with pacemaker implantation.
OBJECTIVE: Escape rhythm is thought to play a considerable role in protection against adverse outcome due to pacemaker malfunction. We studied the escape rhythms in 32 patients with supraventricular tachyarrhythmia refractory to medical therapy who underwent radiofrequency ablation of the atrioventricular junction combined with implantation of a pacemaker. METHODS AND RESULTS: We performed the escape rhythm analysis immediately and 2.6 +/- 1.9 years after the radiofrequency ablation by decreasing the pacing rate. In the initial study, escape rhythms (41 +/- 8 beats/min) were documented in 20 patients (63%). Non-cardiac death occurred in 3 patients with escape rhythm, and cardiac death occurred in I patient without escape rhythm. In the follow-up study, escape rhythms were detected in 22 of 28 patients (79%). Escape rhythm had developed in 6 (55%) of 11 patients who were without escape rhythm initially, while escape rhythm disappeared in 1 of 17 (5.9%) patients who had escape rhythm initially. The changes in escape rhythm were not related to QRS width of the intrinsic beat. There was no correlation between the number of radiofrequency applications or the ratio between atrial and ventricular electrocardiogram voltages of radiofrequency applications and the development of escape rhythms. CONCLUSIONS: The present long-term follow-up study demonstrated that the emergence of an escape rhythm increased several years after ablation, but was unrelated to procedural factors. There are, however, certain patients in whom the disappearance of escape rhythms occur. The evaluation of escape rhythms is thus necessary to determine the risk associated with pacemaker failure.
Aged↗
Modeling the endosomal escape of cell-penetrating peptides: transmembrane pH gradient driven translocation across phospholipid bilayers.
Cell-penetrating peptides (CPPs) are able to mediate the efficient cellular uptake of a wide range of cargoes. Internalization of a number of CPPs requires uptake by endocytosis, initiated by binding to anionic cell surface heparan sulfate (HS), followed by escape from endosomes. To elucidate the endosomal escape mechanism, we have modeled the process for two CPPs: penetratin (pAntp) and the N-terminal signal peptide of the unprocessed bovine prion protein (bPrPp). Large unilamellar phospholipid vesicles (LUVs) were produced encapsulating either peptide, and an ionophore, nigericin, was used to create a transmembrane pH gradient (DeltapH(mem), inside acidic) similar to the one arising in endosomes in vivo. In the absence of DeltapH(mem), no pAntp escape from the LUVs is observed, while a fraction of bPrPp escapes. In the presence of DeltapH(mem), a significant amount of pAntp escapes and an even higher degree of bPrPp escape takes place. These results, together with the differences in kinetics of escape, indicate different escape mechanisms for the two peptides. A minimum threshold peptide concentration exists for the escape of both peptides. Coupling of the peptides to a cargo reduces the fraction escaping, while complexation with HS significantly hinders the escape. Fluorescence correlation spectroscopy results show that during the escape process the LUVs are intact. Taken together, these results suggest a model for endosomal escape of CPPs: DeltapH(mem)-mediated mechanism, following dissociation from HS of the peptides, above a minimum threshold peptide concentration, in a process that does not involve lysis of the vesicles.
Amino Acid Sequence↗
Mechanisms of escape from desmopressin in the rat.
The mechanism(s) of renal escape from the hydro-osmotic effect of vasopressin is unknown. We therefore studied escape in conscious, unrestrained rats receiving continuous intravascular infusions of 1-deamino-8-arginine-vasopressin (desmopressin) and hypotonic fluid over 5 days. Escape from desmopressin started 8 hours after exposure and was characterized by a progressive increase in urine flow and decreases in urine osmolality and free water reabsorption. When positive water balance was prevented by matching the rate of infusion of hypotonic fluid to urine flow while maintaining the dose of desmopressin constant, escape did not occur. This suggested that water retention, rather than chronic exposure to desmopressin, mediated the escape. To elucidate the mechanism whereby water retention induces escape from desmopressin, urinary prostaglandin E2 excretion was measured and found to be increased concomitant with the onset of escape. Prevention of this increase in urinary prostaglandin E2 excretion with indomethacin resulted in additional water retention and a delay in the onset of escape. During the maintenance of escape, after significant water retention occurred, increases in mean arterial pressure, renal blood flow, and glomerular filtration rate were observed. Renal interstitial solute concentration remained constant through escape. Basal and vasopressin-stimulated collecting tubular and thick ascending limb adenylate cyclase did not differ when control and escape animals were compared. These results suggest that enhanced renal synthesis of prostaglandin E2 facilitates the early phase of escape; later, water retention results in plasma volume expansion with increases in cardiac index, arterial pressure, renal blood flow, and glomerular filtration rate. These systemic and renal hemodynamic alterations may be important in maintaining escape from desmopressin.
Animals↗
Expression of vascular escape: conductance or resistance?
Vascular escape is that phenomenon whereby a tachyphylaxis occurs in the vasoconstriction of an arteriole to a constant sympathetic stimulation. Vascular escape, in vivo, is primarily a blood flow event. Calculated resistance, as an index of vascular tone, does not consistently describe the responses of the arterioles undergoing vascular escape. Conductance, which is the inverse of resistance, obviates several of the errors produced by the use of resistance. In this study, we illustrate this issue using hypothetical and experimental data. Escape responses were calculated in terms of resistance and conductance and plotted against blood flow escape responses. Resistance escape responses were nonlinearly related to blood flow escapes and overestimated vascular escape with both hypothetical and experimental data. Conductance escape responses were linearly related to flow escape responses and consistently described vascular escape. We therefore conclude that conductance is a better index of vascular tone to express vascular escape.
Animals↗
Shock controllability and opioid substrates of escape performance and nociception: differential effects of peripherally and centrally acting naltrexone.
Rats exposed to inescapable shock exhibited analgesia and a significant impairment of shock-escape learning in a shuttle box situation 24 hr later. In contrast, rats exposed to escapable shock or to no shock displayed neither effect. Naltrexone (10 mg/kg) significantly reduced the analgesia and completely eliminated the escape deficit in inescapably shocked rats but induced hyperalgesia, coupled with a marked deterioration of escape performance, in escapably shocked and nonshocked rats. The same dose of quaternary naltrexone, which has low ability to cross the blood-brain barrier, had no effect on either the antinociception or the escape deficit produced by inescapable shock, although it also induced escape impairment and hyperalgesia in rats preexposed to escapable shock or to no shock. A second experiment demonstrated that both the escape interference and the antinociceptive consequences of prior inescapable shock could be reduced partially by a much lower dose (1 mg/kg) of naltrexone but 50 times this amount of quaternary naltrexone was still without effect. These results imply that the consequences of exposure to inescapable shock are mediated by activation of central opioid processes whereas naltrexone-induced effects in escapably shocked and nonshocked animals may be peripherally mediated. The relevance of these findings to the possible role of nociception in escape performance is discussed.
Animals↗
Short term escape rhythm characteristics after radiofrequency ablation of the atrioventricular junction.
Radiofrequency ablation of the atrioventricular (AV) node has become an established method of treating drug-resistant supraventricular arrhythmias, especially atrial fibrillation. Although it is routine to implant a permanent pacemaker following ablation, one of the potential adverse effects of the procedure is that many patients become pacemaker-dependent and are at risk of an adverse outcome in the event of pacemaker malfunction. Obtaining information about the characteristics of the escape rhythm would be helpful in risk-stratifying these patients and might facilitate modifications of the procedure that would reduce the incidence of this problem. We prospectively studied the clinical parameters and escape rhythm characteristics in 24 patients undergoing radiofrequency ablation of the AV node. Initially, 2 patients had no detectable escape beats and 4 had escape rates <30 beats/min. At 12 hours, 3 of these 4 had adequate (>30 beats/min) escape rates (there were no 12-hour data in 2). The escape rhythm was stable in 17 of the other 18 while 1 had no escape beats at 12 hours. Patients developing right bundle branch block had a greater chance of having an inadequate escape rhythm at 12 hours but this difference was not seen at 24 hours. We conclude that an adequate escape rhythm is usually present immediately after radiofrequency ablation of the AV node and tends to remain stable up to 24 hours. The absence of an escape rhythm immediately after ablation is of limited prognostic value since reliable escape rhythms may emerge subsequently.
Aged↗
Neutralization escape mutants of type A influenza virus are readily selected by antisera from mice immunized with whole virus: a possible mechanism for antigenic drift.
It is not fully understood how antigenic drift of the haemagglutinin of type A influenza virus in man occurs in the presence of the expected polyclonal antibody response to the five antigenic sites, A to E. Here we show that 12% (11/92) of sera from mice which had mounted a secondary immune response to inactivated influenza virus were able to select escape mutants. No escape mutant was selected with serum from nonimmunized mice (0/65). Selection required only a single passage, and escape mutants were identified by their reaction with monoclonal antibodies (MAbs); all but one had altered reactivity at site A. Most of the site A escape mutants (7/10) were conventional in character and did not react in haemagglutination-inhibition (HI) or neutralization assays with the identifying MAb. The HA genes of three of these were part sequenced and had a predicted single amino acid substitution (Gly-144-->Glu) in site A. The other escape mutants (3/10) had a small (2-fold) reduction in HI and neutralization to the site A MAb, but no amino acid substitution in site A. The final mutant was a conventional site B escape mutant. To model antisera which selected escape mutants, we constructed 'pseudo-immune sera' using mixtures of two neutralizing MAbs in which the first MAb was held at a constant high concentration (1000 HIU/ml). Escape mutants could be selected to the first MAb when the titre of the second MAb was reduced to a low but still inhibiting concentration (1 to 3 HIU/ml). Mixtures of three MAbs also selected escape mutants with similar facility provided that the second and third MAbs were reduced to a similar low concentration. Thus it is possible that the ability of an antiserum to select escape mutants is due to the neutralizing antibody response being biased to an epitope/cross-reacting epitopes within a single antigenic site. However, when escape mutants were reacted in HI assay with their selecting antiserum, the maximum difference from the titre with wt virus was 75%. The findings of this study may be relevant to the understanding of antigenic drift in type A human influenza virus, and to immune-driven antigenic variation in other virus infections.
Animals↗
Vascular escape from vasoconstriction and post-stimulatory hyperemia in the superior mesenteric artery of the cat.
Vascular escape is seen as a partial recovery from initial vasoconstriction despite continued constrictor stimuli. Escape in the feline intestine (superior mesenteric artery) occurred for i.a. norepinephrine (NE) infusions (56% escape for low dose, 40% for high dose NE) and for sympathetic nerve stimulation (SNS) (65% for 1 Hz, 49% for 3 Hz, 44% for 9 Hz). Adenosine infusion or blockade of adenosine receptors (8-phenyltheophylline) did not alter the escape, showing that endogenous adenosine levels are unlikely to play any role in the mechanism of escape. Other aspects of escape were studied: equiconstrictor doses of NE given i.a. or i.v. lead to similar degrees of escape; propranolol and ouabain did not alter escape; the degree of escape was significantly greater for the low dose NE and the 1-Hz SNS than for higher intensities of stimulation, however, escape did not inversely correlate significantly with the initial degree of vasoconstriction when all data were pooled. Post-stimulatory hyperemia occurs upon cessation of vasoconstrictor stimuli, reaches a peak conductance within 1 min, and returns to baseline within about 3 min. Hyperemia was quantitated from the peak vasodilation and from the area under the flow-hyperemia curve. The hyperemias were not related to NE dose or SNS frequency nor did they correlate with initial vasoconstriction or extent of vascular escape. Contrary to the hypothesis that adenosine may mediate hyperemia, adenosine infusions reduced the response and adenosine receptor antagonism tended to elevate the response. Propranolol and ouabain did not produce significant effects on post-stimulatory hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine↗
MOTIVATIONAL ASPECTS OF ESCAPE FROM PUNISHMENT.
Punishment and escape were studied simultaneously by allowing a subject to escape from a stimulus situation in which responses were punished, into a stimulus situation in which responses were not punished. The frequency of the punished responses was found to be an inverse function of the intensity of punishment, whereas the frequency of the escape response was a direct function of the intensity of punishment. Both of these functions were obtained under three different schedules of food reinforcement. The strength of the escape behavior was evidenced by (1) the emergence of the escape response even when the frequency of food reinforcement decreased as a consequence of the escape response, (2) the maintenance of the escape response by fixed-interval and fixed-ratio schedules of escape reinforcement, and (3) the occurrence of escape responses at intensities of punishment that otherwise produced only mild suppression of the punished response when no escape was possible. This last finding indicates that a subject may be driven out of a situation involving punishment even though the punishment is relatively ineffective in suppressing the punished responses when no escape is possible.
Animals↗
A visually evoked escape response of the housefly.
Flies (Musca domestica) avoid danger by initiating a rapid jump followed by flight. To identify the visual cues that trigger the escape response in the housefly, we measured the timing and probability of escapes when the fly was presented with a variety of visual stimuli created by moving targets toward it. Our results show that an escape response is triggered by an approaching dark disk, but not by a receding dark disk. On the other hand, a bright disk elicits escape only when it recedes. A disk with black and white rings is less effective at eliciting escape than is a dark solid disk of the same size. This indicates that the darkening contrast produced by an approaching stimulus is a more crucial parameter than expansion cues contained in the optical flow. Escape is also triggered by a horizontally moving dark edge, but not by a moving bright edge or by a grating. An examination of several visual parameters reveals that the darkening contrast, measured from the onset of stimulation to the start of escape is nearly constant for a variety of stimuli that trigger escape reliably. Thus darkening contrast, coupled with motion may be crucial in eliciting the visually evoked escape response. Other visual parameters such as time-to-contact or target angular velocity seem to be relatively unimportant to the timing of escapes.
Animals↗
A visually elicited escape response in the fly that does not use the giant fiber pathway.
A housefly elicits an escape in response to an approaching target (Holmqvist & Srinivasan, 1991). This study tests if the giant fiber pathway, which mediates a light-off escape response in a fruitfly (Wyman et al., 1985), also mediates escape to an approaching target in a housefly. Visual stimuli simulating an approaching or receding dark disk were presented to houseflies, Musca domestica, in both behavioral and physiological experiments. Freely behaving flies escaped in response to an expanding dark disk but not to a contracting dark disk. In restrained flies, the giant fiber, here called the giant descending neuron (GDN), was recorded from intracellularly and the tergotrochanteral muscle (TTM), which provides the main thrust in an escape jump, was recorded from extracellularly. During electrical stimulation of the brain, by means of stimulating electrodes inserted into the ventral part of each compound eye, a single spike in the GDN drives the TTM. However, when the TTM responds to visual stimulation that elicits an escape response in a behaving fly, the GDN shows no activity. Similarly to the behavioral results, the TTM of restrained flies showed muscle potentials in response to an expanding dark disk, but not to a contracting disk. However, freely moving flies elicit escapes more than 100 ms on average before the first TTM spike, suggesting that this type of escape does not start with a jump powered by the TTM. In conclusion, this visually evoked escape response in the housefly is not likely to be mediated by the giant fiber pathway. The findings suggest that there exist at least two pathways mediating visually evoked escape responses in flies.
Animals↗
Kinematics of aquatic and terrestrial escape responses in mudskippers.
Escape responses in fishes are rapid behaviors that are critical for survival. The barred mudskipper (Periophthalmus argentilineatus) is an amphibious fish that must avoid predators in two environments. We compared mudskipper terrestrial and aquatic escapes to address two questions. First, how does an amphibious fish perform an escape response in a terrestrial environment? Second, how similar is a terrestrial escape response to an aquatic escape response? Because a mudskipper on land does not have to contend with the high viscosity of water, we predicted that, if the same behavior is employed across environments, terrestrial escape responses should have 'better' performance (higher velocity and more rapid completion of movements) when compared with aquatic escape responses. By contrast, we predicted that intervertebral bending would be similar across environments because previous studies of escape response behaviors in fishes have proposed that vertebral morphology constrains intervertebral bending. High-speed digital imaging was used to record mudskipper escapes in water and on land, and the resulting images were used to calculate intervertebral bending during the preparatory phase, peak velocity and acceleration of the center of mass during the propulsive phase, and relative timing of movements. Although similar maximum velocities are achieved across environments, terrestrial responses are distinct from aquatic responses. During terrestrial escapes, mudskippers produce greater axial bending in the preparatory phase, but only in the posterior region of the body and over a much longer time period. Mudskippers also occasionally produced the 'wrong' behavior for a given environment. Thus, it appears that the same locomotor morphology is recruited differently by the central nervous system to produce a distinct behavior appropriate for each environment.
Analysis of Variance↗
Effects of metamorphosis on the aquatic escape response of the two-lined salamander (Eurycea bislineata).
Although numerous studies have described the escape kinematics of fishes, little is known about the aquatic escape responses of salamanders. We compare the escape kinematics of larval and adult Eurycea bislineata, the two-lined salamander, to examine the effects of metamorphosis on aquatic escape performance. We hypothesize that shape changes associated with resorption of the larval tail fin at metamorphosis will affect aquatic locomotor performance. Escape responses were recorded using high-speed video, and the effects of life stage and total length on escape kinematics were analyzed statistically using analysis of covariance. Our results show that both larval and adult E. bislineata use a two-stage escape response (similar to the C-starts of fishes) that consists of a preparatory (stage 1) and a propulsive (stage 2) stroke. The duration of both kinematic stages and the distance traveled during stage 2 increased with total length. Both larval and adult E. bislineata had final escape trajectories that were directed away from the stimulus. The main kinematic difference between larvae and adults is that adults exhibit significantly greater maximum curvature during stage 1. Total escape duration and the distance traveled during stage 2 did not differ significantly between larvae and adults. Despite the significantly lower tail aspect ratio of adults, we found no significant decrease in the overall escape performance of adult E. bislineata. Our results suggest that adults may compensate for the decrease in tail aspect ratio by increasing their maximum curvature. These findings do not support the hypothesis that larvae exhibit better locomotor performance than adults as a result of stronger selective pressures on early life stages.
Animals↗
Ontogeny of squid mantle function: changes in the mechanics of escape-jet locomotion in the oval squid, Sepioteuthis lessoniana lesson, 1830.
In Sepioteuthis lessoniana, the oval squid, ontogenetic changes in the kinematics of the mantle during escape-jet locomotion imply a decline in the relative mass flux of the escape jet and may affect the peak weight-specific thrust of the escape jet. To examine the relationship between ontogenetic changes in the kinematics of the mantle and the thrust generated during the escape jet, we simultaneously measured the peak thrust and the kinematics of the mantle of squid tethered to a force transducer. We tested an ontogenetic series of S. lessoniana that ranged in size from 5 to 40 mm dorsal mantle length (DML). In newly hatched squids, thrust peaked 40 ms after the start of the escape jet and reached a maximum of between 0.10 mN and 0.80 mN. In the largest animals, thrust peaked 70 ms after the start of the escape jet and reached a maximum of between 18 mN and 110 mN. Peak thrust was normalized by the wet weight of the squid and also by the cross-sectional area of the circumferential muscle that provides power for the escape jet. The weight-specific peak thrust of the escape jet averaged 0.36 in newly hatched squid and increased significantly to an average of 1.5 in the largest squids measured (P < 0.01). The thrust per unit area of circumferential muscle averaged 0.25 mN/mm(2) in hatchlings and increased significantly to an average of 1.4 mN/mm(2) in the largest animals tested (P < 0.01). The impulse of the escape jet was also lowest in newly hatched individuals (1.3 mN. s) and increased significantly to 1000 mN. s in the largest squids measured (P < 0.01). These ontogenetic changes in the mechanics of the escape jet suggest (1) that propulsion efficiency of the exhalant phase of the jet is highest in hatchlings, and (2) that the mechanics of the circumferential muscles of the mantle change during growth.
Animals↗
Alteration of escape from rewarding electrical brain stimulation by D-amphetamine.
Rats were trained both to barpress for and escape from locus coeruleus, midbrain periaqueductal gray and hypothalamic stimulation. Rate-intensity functions for intracranial self-stimulation (ICSS) behavior and latency-intensity functions for escape behavior were obtained for each electrode site in each animal. Following baseline, d-amphetamine was administered and responding was compared with the saline condition for both rate-intensity and latency-intensity functions. ICSS response rates were enhanced by d-amphetamine at all loci, particularly at threshold intensities, while escape responding was biphasically affected by d-amphetamine at all loci. D-amphetamine increased escape latencies at intensities which, under saline, elicited short escape latencies, while decreasing escape latencies at intensities which, under saline, elicited long escape latencies. A significant correspondence was noted between intensities which, under the influence of d-amphetamine, both elicited longer escape latencies and higher ICSS response rates, suggesting that in both ICSS and escape paradigms, animals were titrating the duration of the stimulus train. No site-specific effects of d-amphetamine upon escape behavior were noted.
Animals↗