Post-stimulation Recovery Research Articles

Heart rate dynamics and asymmetry during sympathetic activity stimulation and post-stimulation recovery in ski mountaineers-a pilot exploratory study.

There is a lack of studies on non-linear heart rate (HR) variability in athletes. We aimed to assess the usefulness of short-term HR dynamics and asymmetry parameters to evaluate the neural modulation of cardiac activity based on non-stationary RR interval series by studying their changes during sympathetic nervous system activity stimulation (isometric handgrip test) and post-stimulation recovery in professional ski mountaineers. The correlation between the changes in the parameters and the respiratory rate (RespRate) and also the duration of the career was analyzed. Short-term (5 min) and ultra-short-term (1 min) rates of patterns with no variations (0V), number of acceleration runs of length 1 (AR1), and short-term Porta's Index were greater, whereas Guzik's Index (GI) was smaller during sympathetic stimulation compared to rest. GI increased and the number of AR1 decreased during recovery. Greater increases in GI and RMSSD were associated with greater decreases in RespRate during recovery. Greater increases in RespRate from rest to short-term sympathetic stimulation were associated with greater increases in 0V (Max-min method) and AR1 but also with greater decreases in decelerations of short-term variance and accelerations and decelerations of long-term variance. Greater increases in 0V (Max-min method) and number of AR1 during sympathetic stimulation were associated with a shorter career duration. Greater decreases in these parameters during recovery were associated with a longer career duration. Changes in measures of HR dynamics and asymmetry, calculated based on short-term non-stationary RRi time series induced by sympathetic stimulation and post-stimulation recovery, reflected sympathovagal shift and were associated with condition-related alterations in RespRate and career duration in athletes who practice ski mountaineering.

Limited storage and recovery of adsorbed gas in shale reservoirs - Insights from experiments and production modeling

Gas in thermally mature shale reservoirs is considered to exist as adsorbed volume in organic matter and free gas within pores and voids in natural fractures. Gas in-place is derived from summation of aforementioned volumes. Although industry has adopted laboratory-based adsorption isotherms, quantification is still uncertain and questions on recoverability still linger. This study reevaluated in-place adsorbed gas and post-stimulation recovery. Two proprietary laboratories, using small and large mesh sizes, generated different adsorption isotherms for comparable samples of a Middle East source rock. In addition, review of published experimental studies led to the realization that confining pressures as those in situ were seldomy replicated and derived isotherms exhibited wide variability. A hypothetical scenario, using benchmarked adsorption isotherms illustrated impacts of unreliable adsorbed volume quantification on total gas in-place. From analysis of well production for three shales, matrix transient linear flow persisted for extended periods without indicating influence of boundaries. The flow regime is often matched by considering only free gas porosity. Using a sector model with 1.0 nanodarcy (nD) system permeability in reservoir simulation, a considerable proportion of the adopted grid remained above a benchmarked average critical desorption pressure after long-term post-stimulation drainage. Thus, desorption could be of limited significance in shale production if the flow model was appropriate. This study illustrated uncertainties in traditional concepts for shale gas storage and recovery. Realistic quantification of in-place adsorbed gas was found to require tailoring of laboratory protocols to account for crushed sample sizes and confinement that should match subsurface conditions such as effective vertical stress.

Theoretical perspectives on central chemosensitivity: CO2/H+-sensitive neurons in the locus coeruleus.

Central chemoreceptors are highly sensitive neurons that respond to changes in pH and CO2 levels. An increase in CO2/H+ typically reflects a rise in the firing rate of these neurons, which stimulates an increase in ventilation. Here, we present an ionic current model that reproduces the basic electrophysiological activity of individual CO2/H+-sensitive neurons from the locus coeruleus (LC). We used this model to explore chemoreceptor discharge patterns in response to electrical and chemical stimuli. The modeled neurons showed both stimulus-evoked activity and spontaneous activity under physiological parameters. Neuronal responses to electrical and chemical stimulation showed specific firing patterns of spike frequency adaptation, postinhibitory rebound, and post-stimulation recovery. Conversely, the response to chemical stimulation alone (based on physiological CO2/H+ changes), in the absence of external depolarizing stimulation, showed no signs of postinhibitory rebound or post-stimulation recovery, and no depolarizing sag. A sensitivity analysis for the firing-rate response to the different stimuli revealed that the contribution of an applied stimulus current exceeded that of the chemical signals. The firing-rate response increased indefinitely with injected depolarizing current, but reached saturation with chemical stimuli. Our computational model reproduced the regular pacemaker-like spiking pattern, action potential shape, and most of the membrane properties that characterize CO2/H+-sensitive neurons from the locus coeruleus. This validates the model and highlights its potential as a tool for studying the cellular mechanisms underlying the altered central chemosensitivity present in a variety of disorders such as sudden infant death syndrome, depression, and anxiety. In addition, the model results suggest that small external electrical signals play a greater role in determining the chemosensitive response to changes in CO2/H+ than previously thought. This highlights the importance of considering electrical synaptic transmission in studies of intrinsic chemosensitivity.

Exacerbated in vivo metabolic changes suggestive of a spontaneous muscular vaso-occlusive crisis in exercising muscle of a sickle cell mouse

While sickle cell disease (SCD) is characterized by frequent vaso-occlusive crisis (VOC), no direct observation of such an event in skeletal muscle has been performed in vivo. The present study reported exacerbated in vivo metabolic changes suggestive of a spontaneous muscular VOC in exercising muscle of a sickle cell mouse. Using magnetic resonance spectroscopy of phosphorus 31, phosphocreatine and inorganic phosphate concentrations and intramuscular pH were measured throughout two standardized protocols of rest – exercise – recovery at two different intensities in ten SCD mice. Among these mice, one single mouse presented divergent responses. A statistical analysis (based on confidence intervals) revealed that this single mouse presented slower phosphocreatine resynthesis and inorganic phosphate disappearance during the post-stimulation recovery of one of the protocols, what could suggest an ischemia. This study described, for the first time in a sickle cell mouse in vivo, exacerbated metabolic changes triggered by an exercise session that would be suggestive of a live observation of a muscular VOC. However, no evidence of a direct cause-effect relationship between exercise and VOC has been put forth.

Modulation of the honey bee ( Apis mellifera) sting response by octopamine

The ability of octopamine (OA) to modulate various parameters of the honey bee sting response was observed using an isolated abdominal preparation. OA reduced the level of rhythmic neuromuscular activity (as measured by electromyogram recordings) during stimulated stinging response trials, but did not alter the activity in pre-stimulation baseline trials or post-stimulation recovery trials. However, OA also potentiated reflexive sting extension responses and this potentiation persisted for at least 3 h. The different effects of OA on this behavior indicate that there are multiple targets for the neuromodulatory activity of OA on the sting response and that these targets may include muscular, motorneural, sensory or integrative elements responsible for generating stinging behavior. In addition, rates of oxygen (O 2) consumption by abdominal preparations were found to be unaffected by OA treatment, indicating that respiration in the abdomen is not sensitive to OA modulation.

Recovery after intense chronic stimulation: a physiological study of cat's fast muscle

Adult cats were used to study the recovery of muscles that had become altered by long-term electrical stimulation. Chronic activation was delivered to the deafferented common peroneal nerve (no pain, no reflexes), and contractile properties were measured for peroneus longus muscle. After 4 wk of great daily amounts of treatment at moderately high pulse rates (30-40 Hz delivered during 50% of daily time), the peroneus longus became considerably weaker, demonstrated a longer time course of twitches and a slower rate of rise of tetanic force, and became less fatigable. Furthermore, its twitch-to-tetanus ratio decreased, and there was no longer any depression of electromyogram (EMG) amplitude during fatigue tests. After 4 wk of subsequent rest it was found that 1) twitch speed and maximum tetanic force had returned to nearly normal values, 2) fatigue resistance showed some return toward normal but was still significantly enhanced, and 3) no significant recovery had yet occurred of the altered twitch-to-tetanus ratio, the abolished EMG depression, or the slowed rate of rise of tetanic tension. During the poststimulation recovery period, the progressive increase of isometric twitch speed was not promoted by the administration of small daily amounts of high-rate stimulation (100-Hz bursts). The results support the conclusions that 1) the time course of recovery differs among physiological properties, 2) the EMG and force reactions that occur during a fatigue test are not strongly coupled, as demonstrated by the alterations of their relationship during poststimulation recovery, and 3) in cat's fast muscles, there is still no evidence for rate-specific effects of chronic stimulation on isometric twitch speed.

Frequency‐dependent and cell‐specific effects of electrical activity on growth cone movements of cultured Helisoma neurons

The present experiments address the question of how stimulation parameters, which evoke action potentials in neuronal cell bodies, influence growth cone movements of different identified neurons. The motility of growth cones of Helisoma buccal neurons B19 and B4 was monitored while somata were stimulated simultaneously via an intracellular microelectrode. The findings show that the responses of growth cones of B19 and B4 contain components that are common as well as unique to each neuron. Whereas rates of growth cone advance were suppressed in a graded fashion by stimulus frequencies beyond a threshold of 2 s-1 for both neurons, B4 was more sensitive to electrical stimulation and exhibited a new response, namely, growth rates were enhanced during the poststimulation recovery period after stimulation at specific frequencies. Thus, electrical activity can result in enhancement as well as in inhibition of growth cone movement. Changes in number of filopodia on B19 and B4 were graded also, with B4 again displaying greater sensitivity. The frequency dependence of filopodia compared to growth rate changes was different and suggests a possible dissociation between filopodial activity and growth cone motility. Patterned electrical activity produced effects similar to constant stimulation for B19 growth cones, whereas it decreased the threshold frequency and eliminated the growth enhancement effect for B4. Taken together, these data demonstrate that the quantitative features of electrical activity as well as intrinsic properties of neurons both determine the growth cone response to changes in neuronal activity.

Glucose dependence of sequential norepinephrine contractions of vascular smooth muscle.

The effects of successive, norepinephrine (NE)-stimulated, contractions of porcine carotid artery intima-media strips as a function of recovery medium were studied. Recovery following NE stimulation required the presence of glucose in the bathing medium for subsequent force production in response to NE stimulation. Potassium stimulation following failed NE contractions produced maximal contractions. Phosphorous nuclear magnetic resonance studies under similar conditions indicated that the energy state of the tissue was not impaired during and after recovery from NE stimulation without glucose. This study shows that the phasic phase of norepinephrine-stimulated contractions is dependent on the availability of extracellular glucose during the poststimulation recovery period for successive NE contractions.

Modification of the frequency- and voltage-dependent effects of quinidine when administered in combination with tocainide in canine Purkinje fibers.

Frequency- and voltage-dependent modification of drug-induced inhibition of maximal upstroke velocity of the action potential (Vmax) by the combined administration of two class I antiarrhythmic drugs was studied in canine Purkinje fibers, taking depression of upstroke velocity as an indicator of sodium channel blockade. The kinetics of onset of drug-induced Vmax depression and the time course of Vmax recovery were studied after exposure to therapeutic concentrations of tocainide (50 microM) and quinidine (5 microM) both singly and in combination. The rate constant for onset of block during a drive train at a cycle length of 600 msec was 0.95 +/- 0.32 pulses in the presence of tocainide and 5.61 +/- 0.50 pulses in the presence of quinidine. The magnitude of block was three times greater with quinidine than with tocainide. The magnitude of block produced by the combination was no greater than that produced by quinidine alone and may be partly due to abbreviation of action potential duration by tocainide. Onset of block in the presence of the combination was best fitted by a double exponential with rate constants of 0.88 +/- 0.19 and 6.47 +/- 1.36 pulses. Vmax recovery after termination of a rapid train of impulses was delayed by both drugs. Poststimulation recovery from either tocainide- or quinidine-induced block was characterized by a single time constant (1.04 +/- 0.49 and 4.81 +/- 0.76 sec, respectively), while that of the combination was characterized by two time constants (0.43 +/- 0.22 and 5.94 +/- 0.56 sec), presumably corresponding to dissociation of each drug from the sodium channel receptor. The mixture of the two drugs produced a large depression of Vmax of early diastolic premature responses without producing much further depression of Vmax than that produced by quinidine alone at longer coupling intervals. The time constant of recovery from tocainide-induced block was greatly dependent upon membrane potential. After steady-state changes in frequency, the combination produced a greater depression of Vmax at rapid heart rates compared with that produced by quinidine alone, but abbreviated action potential duration more at slower heart rates. Addition of tocainide to fibers equilibrated with quinidine shifted the Vmax-membrane potential relationship to more hyperpolarized potentials, resulting in greater depression of Vmax at more depolarized membrane potentials with little or no additional depression of Vmax at more negative membrane potentials. The results provide a rationale for a possible enhanced antiarrhythmic efficacy of a combination of two class I drugs that have different kinetics of interaction with the sodium channel.

Evidence for a specific receptor site for lidocaine, quinidine, and bupivacaine associated with cardiac sodium channels in guinea pig ventricular myocardium.

According to the modulated receptor hypothesis, sodium channels have a specific receptor site for local anesthetic and antiarrhythmic drugs. Thus, in the presence of a high concentration of two drugs, competitive displacement of one drug by another may occur. Furthermore, if a drug that has relatively rapid post-stimulation recovery kinetics (e.g., lidocaine) displaces another drug with relatively slow recovery kinetics (i.e., quinidine or bupivacaine), then a net reduction in sodium channel blockade is expected at certain stimulation rates. We tested this prediction, using the maximum upstroke velocity of the ventricular action potential as an indicator of drug-free sodium channels. A single sucrose gap technique was used to stimulate guinea pig papillary muscles, and to control membrane voltage at all times except during the action potential upstroke. Drug-induced inhibition of maximum upstroke velocity increased as the stimulation rate was increased, and was significant (P less than 0.05) at stimulation rates between 2.5 and 4 Hz in the presence of 43 microM lidocaine (n = 5), and between 0.15 and 4 Hz in the presence of 3.5 microM bupivacaine (n = 4). The addition of 43 microM lidocaine to a perfusate containing 3.5 microM bupivacaine resulted in a net increase in maximum upstroke velocity that was significant at rates between 1 and 3.3 Hz, with a maximum increase of 25 +/- 6% at 1.6 Hz. In contrast, addition of 43 microM lidocaine to a perfusate containing 15 microM quinidine did not result in a significant change in maximum upstroke velocity at driving rates between 0.05 and 3.3 Hz (P greater than 0.2; n = 4). However, evidence for displacement of quinidine by lidocaine could be demonstrated by measuring post-stimulation recovery after a conditioning train of 19 10-msec pulses applied at 28 Hz. With this stimulation protocol, 41 +/- 4% of maximum upstroke velocity recovered slowly from block with a time constant of 3.7 +/- 1.2 seconds at - 100 mV in the presence of 15 microM quinidine (n = 5). In the presence of a mixture of 43 microM lidocaine and 15 microM quinidine, this slow component was significantly reduced to 16 +/- 7% (n = 5; P less than 0.01), while 71 +/- 13% of maximum upstroke velocity recovered with a time constant of 115 +/- 21 msec, typical of lidocaine-blocked channels. A two-drug version of the modulated receptor theory was formulated. The effects of drug mixtures could be accounted for by this model.(ABSTRACT TRUNCATED AT 400 WORDS)

Initiation of Erection and Semen Release by Rectal Probe Electrostimulation (RPE)

Instrumentation and methodology are described for rectal probe electrostimulation (RPE) in human males to elicit erection and allow semen collection. This system virtually eliminates shock hazard; the simultaneous monitoring of current, voltage and impedance ensures reliability and repeatability. It was tested with 8 neurologically intact subjects, and 12 paraplegic patients with lesions between T4 and L2. Platinum electrodes delivered current (density never exceeding 0.37mA permm.2 at the electrode) at frequencies of 60Hz, 20Hz, and 0.25Hz. Erection was elicited repeatably in only 1 of the intact subjects, and no seminal emissions or ejaculations occurred. Discomfort prevented current delivery beyond levels even 50 per cent of those safely acceptable. Six of 10 paraplegic patients (2 others had penile implants) developed erections with 20 Hz; the other 2 frequencies were much less effective. The extent of RPE-induced penile tumescence varied directly with electrode surface area and applied current intensity. Discomfort was minimal. Retrograde seminal emission in 5 of the 12 paraplegics was verified by post-stimulation recovery of sperm via voiding or bladder irrigation via catheter. Although motility was very low, 4 of 8 recovered bladder-urine/seminal fluid specimens indicated sperm counts and morphology consonant with use in artificial insemination. Thus, RPE, if combined with techniques to allow antegrade semen collection, may be a useful technique for spinal cord-injured men who, as part of their sexual rehabilitation, are interested in siring children.

Frequency-dependent depression of Vmax of slow response action potentials by a high concentration of papaverine.

The maximum upstroke velocity (Vmax) of Ca2+-dependent action potentials was used to measure relative changes in the slow inward current (Isi) caused by 10(-4) M papaverine as a function of pacing frequency in K-depolarized guinea pig ventricular strips. Papaverine caused a pronounced frequency-dependent depression of Vmax presumed to be correlated with a decrease in the rate of recovery from inactivation of Isi. Papaverine (10(-4) M) tripled the time constants for the biexponential recovery from depression of Vmax (determined by a paired pulse protocol) relative to the control. Depression of Vmax by papaverine during a 1 Hz stimulus train preceded by a long rest period reached a new steady state within three depolarizations. Complete poststimulation recovery from the depression of Vmax was also relatively rapid, unlike that described for verapamil. Preparations exposed to Mn2+ (after pretreatment with Ba2+ to restore excitability) showed a depressed steady-state Vmax independent of frequency. It is concluded that the frequency-dependent blockers of Vmax (papaverine and verapamil) differ in their rates of association and dissociation with the slow inward channel.

Noradrenaline and dopamine-beta-hydroxylase levels in rat salivary glands after preganglionic nerve stimulation: evidence for re-use of amine storage granules in transmitter release.

The levels of endogenous noradrenaline (NA) in rat salivary glands were reduced to about 40 per cent after 1 hour of preganglionic stimulation at 4 Hz. Following 2 to 3 hours of rest the NA values had recovered to normal and remained normal for 6 hours after the stimulation. The recovered NA could be depleted by renewed nerve stimulation. After treatment with reserpine the NA disappeared almost completely. The recovered NA is discussed to be mainly present in amine storage granules that are re-used for storage and transmitter release. The axonal down-transport of new granules to the nerve terminals appears to be too small, as based on earlier results, for being of any quantitative importance in the experimental situation. The dopamine-beta-hydroxylase (DBH) level in the glands did not significantly change after the period of stimulation. The DBH content remained mainly unchanged following either post-stimulation recovery, repeated stimulation, or reserpine treatment. First when the glands were stimulated for 4 hours, there was a small decrease of the DBH levels. The mainly unchanged levels of DBH after stimulation does not appear to be explained by "trapping" in the tissue of released DBH, or recovery of the DBH by a marked axonal down-transport of new granules, as based on earlier results. The results of the DBH estimations support the view that the granules are not consumed to any marked extent at nerve activity, but can be re-used for nerve transmission. Furthermore, the results are in agreement with lack of correlation between released NA and released DBH.

Electrophysiological effect of overdrive suppression and combined autonomic blockade with propranolol and atropine in patients with sinus node dysfunction

The phenomenon of sinus node depression and recovery after rapid atrial pacing was studied in 36 patients before and after the combined administration of atropine and propranolol. Sinus node recovery time was measured, and the first 10 cycles following cessation of atrial pacing (‘secondary phase’) were evaluated. During the pharmacological test, the observed intrinsic heart rate was compared with theoretical values. Altered electrophysiological parameters were observed during the post-stimulation sinus node depression in all patients having an abnormal intrinsic heart rate. In patients with a normal intrinsic heart rate the electrophysiological study of the sinus node gave either normal or abnormal results. In the latter case, the possibility that altered electrophysiological parameters could result from functional' sinus node dysfunction is to be considered. Although the intrinsic heart rate may be normal, pacemaker cells could have disorders of their intrinsic electrophysiological mechanisms. Abnormalities observed during the secondary phase after autonomic blockade in patients with a previously unaltered post-stimulation recovery phase strongly support such a view. This study emphasises the diagnostic value of the behaviour of the secondary phase to distinguish between functional sinus node disorders and organic changes of the pacemaker cells.

Test of a model of antiarrhythmic drug action. Effects of quinidine and lidocaine on myocardial conduction.

The effects of quinidine and lidocaine on the maximum upstroke velocity (Vmax) of the ventricular myocardial action potential were compared with the effects predicted by a model over a wide range of driving rates, rhythm disturbances and holding potentials. These rate-, rhythm- and voltage-dependent effects were accurately predicted by the proposed model. The model was also able to predict several previously undocumented properties of the drugs: 1) If lidocaine decreases Vmax of a pulse train, the steady state is reached within a few action potentials. 2) The poststimulation recovery of Vmax in the presence of lidocaine or quinidine can occur in a multiexponential fashion, if the membrane potential is kept at the potential where both the fast (operating mainly at more negative membrane potentials) and the slow (operating at more positive potentials) recovery processes are operative. 3) Hyperpolarization markedly attenuates the rate-dependent drug effects. 4) Combinations of lidocaine and quinidine have a superadditive effect on the Vmax of early extrasystoles.

Selective depression of 2,4-dinitrophenol depolarized canine Purkinje fibers by lidocaine.

Concentrations of lidocaine which minimally decrease conduction and excitability of normal canine Purkinje fibers markedly decrease these parameters in fibers depolarized by metabolic depression (DNP superfusion). The decrease in Vmax and the slowing of the post-stimulation recovery of Vmax by lidocaine are also more marked during DNP superfusion than during superfusion with a DNP-free salt solution. Since these effects could be reversed by a lidocaine-free DNP superfusion, it is concluded that lidocaine selectivity depresses the electrical activity of tissue depolarized by the metabolic inhibitor DNP. This selective depressive action of lidocaine is similar to that observed in cardiac tissues depolarized by other means.

The effect of high level sound on hearing sensitivity, cochlear sensorineuroepithelium and vasculature of the chinchilla.

Ten young chinchilla were tested for hearing and then exposed for 8 hours to a 110 dB (SPL) broad-band noise. Post-stimulation recovery was assessed daily until permanent threshold shifts were obtained. Cochlear tissues were prepared in order to allow viewing of sensory cells as well as the vascular supply of the cochlea. Findings included inconsistent displacement of the vestibular membrane, poor injection of a contrast medium into vessels, moderate outer hair cell loss and displaced inner hair cell nuclei. Small basal turn cell damage was accompanied by greater than expected losses for high frequency pure tones.