Mathematical model of acetylcholine kinetics in neuroeffector junctions

1994 ◽  
Vol 266 (1) ◽  
pp. H298-H309 ◽  
Author(s):  
F. Dexter ◽  
Y. Rudy ◽  
G. M. Saidel
Keyword(s):  
Mathematical Model ◽  
Heart Rate ◽  
Rate Coefficient ◽  
Sinus Node ◽  
Vagal Activity ◽  
Pacemaker Cells ◽  
Order Linear ◽  
First Order ◽  
Linear Kinetics ◽  
The Mean

Acetylcholine (ACh) kinetics in neuroeffector junctions (NEJ) of the sinus node plays a key role in vagal control of heart rate. Prior studies have shown that the concentration of ACh ([ACh]) in NEJ appears to follow first-order linear kinetics. To find out the reason why, we examine mathematically diffusion, degradation, and receptor binding of ACh in NEJ. We identify seven conditions that potentially influence ACh kinetics. Because these conditions are satisfied for NEJ in the sinus node, 1) the nonlinearity of ACh binding to muscarinic receptors has little effect on [ACh]; 2) [ACh] does not depend on the distribution of acetylcholinesterase between the interstitial space and the pacemaker cells; 3) the interval from trough to subsequent peak [ACh] at the pacemaker cells is negligible; 4) the mean [ACh] at the pacemaker cells is proportional to the frequency of vagal activity multiplied by the amount of ACh released per vagal stimulus and divided by the rate coefficient of ACh degradation; and 5) [ACh] at pacemaker cells nearly follows first-order linear kinetics but does not at other sites in the NEJ. We conclude that earlier studies showed that [ACh] follows first-order linear kinetics, because they predicted [ACh] only at pacemaker cells. ACh kinetics at other sites in the NEJ, such as at nerve endings, is different.

Effects of repetitive bursts of vagal activity on atrioventricular junctional rate in dogs

1979 ◽  
Vol 237 (3) ◽  
pp. H275-H281 ◽  
Author(s):  
D. W. Wallick ◽  
M. N. Levy ◽  
D. S. Felder ◽  
H. Zieske
Keyword(s):  
Cardiac Cycle ◽  
Sinus Node ◽  
Critical Time ◽  
Large Change ◽  
Vagal Activity ◽  
Vagus Nerves ◽  
Pacemaker Cells ◽  
Chronotropic Response ◽  
Sinus Node Artery ◽  
The Mean

A stable atrioventricular (AV) junctional rhythm was produced in open-chest dogs by injecting pentobarbital into the sinus node artery. When the cervical vagus nerves were stimulated repetitively, the junctional pacemaker cells tended to become synchronized with the vagal activity. During such synchronization, the junctional rate varied directly rather than inversely with the frequency of vagal stimulation. The magnitude of the chronotropic response depended on the timing of the vagal stimuli within the cardiac cycle. In 9 dogs, when the mean heart periods were plotted as a function of the R-st intervals (i.e., the time from the beginning of ventricular depolarization to the beginning of the stimulus burst), the mean heart periods varied from a maximum of 1,815 ms to a minimum of 1,160 ms, depending on the R-st interval. A small change in the R-st interval was capable of evoking a relatively large change in cycle length. Therefore, the impulses from various efferent vagal fibers to the AV junction must arrive almost synchronously, the released acetylcholine must be removed rapidly, and the sensitivity of the pacemaker cells to acetylcholine must change rapidly at some critical time during the cardiac cycle.

Mechanistic Information on the Aquations of Complexes of the Pentaamminecobalt(III) Series from Kinetic Studies at High Pressures

1972 ◽  
Vol 50 (17) ◽  
pp. 2739-2746 ◽  
Author(s):  
W. E. Jones ◽  
L. R. Carey ◽  
T. W. Swaddle
Keyword(s):  
High Pressures ◽  
Rate Coefficient ◽  
Kinetic Studies ◽  
Quadratic Equation ◽  
Water Molecules ◽  
First Order ◽  
Unit Slope ◽  
Straight Line ◽  
The Mean ◽  
The Stability

The logarithm of the pseudo-first-order rate coefficient k for the aquation of Co(NH3)5X(3–n)+ can be represented by a quadratic equation in the pressure P, or, better, by[Formula: see text]where P is in kbar, [Formula: see text] is the volume of activation at P = 0, and x is the increase in the number of water molecules solvating the complex as it goes to the transition state. For [Formula: see text]Cl−, Br−,[Formula: see text] and [Formula: see text] at 25° [Formula: see text] and ionic strength I = 0.1 M LiClO4/HClO4, [Formula: see text] −10.6, −9.2, −6.3, and +16.8 cm3 mol−1, and x = 8.0, 4.1, 3.9, 1.9, and −4.2; for Xn− = NCS−, the mean ΔV* from P = 0.001 to 2.5 kbar at 88° is −4 cm3 mol−1. Detailed consideration of these data, especially their correlation with the molar volume of reaction by a straight line of unit slope for [Formula: see text] Cl−, Br−, NO3−, and H2O, provides strong evidence for a dissociative interchange mechanism. For [Formula: see text] the separating entity is probably HN3 rather than [Formula: see text] For Xn− = NCS−, aquation is incomplete, at practical complex concentrations; at 88.0°, 1 bar, and I = 0.1 M LiClO4/HClO4, k = 3.3 × 10−6 s−1 and the stability constant of Co(NH3)5NCS2+ is 490 M−1.

scholarly journals The Chronotropic Function of Propofol and the Underlying Mechanism in Rabbits

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Wenjie Cheng ◽  
Xiaohua Sun ◽  
Yanfang Liu ◽  
Shiqi Han ◽  
Wanlu Ren
Keyword(s):  
Heart Rate ◽  
Action Potentials ◽  
Sinus Node ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Pacemaker Cells ◽  
Concentration Dependent Manner ◽  
Sinoatrial Nodes ◽  
Chronotropic Action ◽  
Dose Dependent

The report of bradycardia caused by propofol is increasing. In the experiment, we investigated the chronotropic function of propofol and the underlying mechanism. Rabbits of both sexes were randomly divided into 4 groups: propofol 5 mg/kg group, 10 mg/kg group, 15 mg/kg group, and sham group. Heart rate and frequency of vagal efferent discharge were recorded before the injection and 0, 0.5, 1, 2, and 10 min after the injection through intravenous mode. Then, their hearts were removed, and sinoatrial nodes were dissected. The action potentials of the sinus node pacemaker cells were recorded by the intracellular glass microelectrode technique, and the sinoatrial (SA) node was exposed to propofol 1, 3, 5, and 10 µM respectively. The action potentials were recorded after the sinoatrial nodes were exposed to each concentration of propofol for 15 min. Our results show that the heart rate significantly decreased, and the vagal efferent discharge was significantly increased at 0, 0.5, 1, and 2 min after the injection, respectively. Besides, as the dose increases, the magnitude of change shows a dose-dependent manner. Propofol exerts a negative chronotropic action on sinoatrial node pacemaker cells. The drug significantly decreased APA, VDD, RPF, and prolonged APD90 in a concentration-dependent manner. These effects may be the main mechanism of propofol-induced bradycardia in clinical study.

Evidence for time-dependent autonomic cardiac reinnervation in children subsequent to transplantation of the heart

1996 ◽  
Vol 6 (1) ◽  
pp. 12-19
Author(s):  
Joachim Kreuder ◽  
Heinrich Netz ◽  
Thomas Paul ◽  
Andreas Müller ◽  
Jürgen Bauer ◽  
...  
Keyword(s):  
Heart Rate ◽  
Standard Deviation ◽  
Time Domain ◽  
Recovery Time ◽  
Cardiac Transplantation ◽  
Sinus Node ◽  
Time Dependent ◽  
Rr Intervals ◽  
The Mean ◽  
Frequency Power

AbstractAutonomic denervation has been assumed to persist after orthotopic heart transplantation. Analyzing spontaneous and induced variations of heart rate, the status of autonomic cardiac innervation was investigated in six children 19–37 months after cardiac transplantation. The age at the time of transplantation varied from three weeks to 15.4 years. Heart rate variability was assessed on 24-hour Holter recordings by calculating time-domain indices (standard deviation of all RR intervals; standard deviation of the mean RR intervals from successive five-minute periods; mean of the standard deviations of RR intervals from successive five-minute periods; proportion of adjacent RR intervals > 50 msec different; square root of mean square successive differences in RR intervals) and frequency-domain variables (low frequency power, high frequency power and total spectrum power). Sinus node recovery time, sinoatrial conduction time and post-pacing cycle lengths were examined at different rates of endocardial atrial pacing. After the first year subsequent to transplantation, standard deviation of the mean RR intervals reached the normal range in four patients, whereas the other time-domain variables became normal in two patients. Both patients displayed normal or near-normal power spectrums of heart rate with normal day-to-night variations. For the remaining patients, spectrums of heart rate failed to show the main frequency peaks. Only the patient with normal variability in heart rate exhibited a decrease in corrected sinus node recovery time at higher stimulation rates, shortening of the first recovery cycle below the pre-pacing level, and a rapid decline of the accelerated post-pacing heart rate as described in innervated hearts. These results suggest the evolution of time-dependent efferent autonomic reinnervation after cardiac transplantation in children.

Distribution of Movement Time in a Target-Aiming Task

1976 ◽  
Vol 43 (2) ◽  
pp. 507-513 ◽  
Author(s):  
Tarald O. Kvålseth
Keyword(s):  
Experimental Data ◽  
Standard Deviation ◽  
Normal Distribution ◽  
Linear Model ◽  
Movement Time ◽  
Arm Movements ◽  
Order Linear ◽  
First Order ◽  
Index Of Difficulty ◽  
The Mean

Various characteristics of the distribution of movement time were analyzed for a task involving serial and rotary arm movements aimed at a target. For experimental data generated from five Ss, (a) the distribution tended to be unimodal and more peaked than a normal distribution, (b) the skewness of the distribution was predominantly positive and (c) the standard deviation, in addition to the mean, of movement time was significantly affected by the complexity of the task as measured by Fitts' index of difficulty, while the skewness and the kurtosis were not. For the average results for the Ss, a first-order linear model with the standard deviation of movement time as the dependent variable and Fitts' index as the independent one explained 67% of the variation in standard deviation as compared to 98% of the variation in mean movement time accounted for by the Fitts' index.

Pertussis toxin-induced ADP ribosylation of inhibitor G proteins alters vagal control of heart rate in vivo

1993 ◽  
Vol 265 (2) ◽  
pp. H734-H740 ◽  
Author(s):  
P. B. Adamson ◽  
S. S. Hull ◽  
E. Vanoli ◽  
G. M. De Ferrari ◽  
P. Wisler ◽  
...  
Keyword(s):  
Heart Rate ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Baroreflex Sensitivity ◽  
Submaximal Exercise ◽  
Conscious Dogs ◽  
Vagal Activity ◽  
Adp Ribosylation ◽  
The Mean

Prior studies have shown that in vivo systemic administration of pertussis toxin in conscious dogs catalyzes ADP ribosylation of Gi and G(o) proteins, which attenuates intracellular transduction of muscarinic receptor activation. We tested the hypothesis that this impairment may result in the alteration of the following indexes of cardiac vagal activity: baroreflex sensitivity and heart rate variability. Heart rates during submaximal exercise were also determined. These variables were measured in eight conscious dogs before and 72 hr after pertussis toxin administration. Pertussis toxin significantly reduced (P < 0.001) baroreflex sensitivity (from 18.7 +/- 2.6 to 6.8 +/- 1.4 ms/mmHg), the SD of the mean R-R intervals (from 176 +/- 17 to 61 +/- 7 ms), the mean R-R interval (from 742 +/- 32 to 527 +/- 29 ms), and the coefficient of variance [from 235 +/- 15 to 114 +/- 1 (x 1,000)]. The heart rate response to graded submaximal exercise after pertussis toxin was higher (P < 0.001) at each exercise level. In in vitro assay, cardiac tissue samples from pertussis toxin-treated dogs incorporated 10-fold less ADP ribose than what has been described previously. These data prove that the in vivo action of pertussis toxin on cardiac inhibitory G proteins has direct consequences on end-organ cardiac responses to vagal activity. This study quantifies the physiological consequences of pertussis toxin-induced impairment of inhibitory G proteins in conscious animals.

Autonomic control of pacemaker activity in the atrioventricular junction of the dog

1978 ◽  
Vol 235 (3) ◽  
pp. H308-H313 ◽  
Author(s):  
D. W. Wallick ◽  
D. Felder ◽  
M. N. Levy
Keyword(s):  
Sinus Node ◽  
Pacemaker Activity ◽  
Vagal Activity ◽  
Sympathetic Stimulation ◽  
Pacemaker Cells ◽  
Junctional Rhythm ◽  
Group Of Seven ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
High Level

A stable atrioventricular (AV) junctional rhythm was induced in open-chest, anesthetized dogs by injecting pentobarbital into the sinus node artery. A factorial experimental design was used to quantify the changes in AV junctional rate as a function of the frequency of cardiac sympathetic and parasympathetic stimulation. The AV junctional pacemaker cells were more responsive to autonomic neural stimulation, but the vagal-sympathetic interactions were less pronounced than had previously been observed for the SA nodal pacemaker cells. In a group of seven animals, sympathetic stimulation at a frequency of 1.4 Hz increased the AV junctional rate by 102% from a control rate of 54 beats/min. In the same animals, vagal stimulation at a frequency of 8.4 Hz reduced the AV junctional rate by 56%. In three other animals, the AV junction was even more responsive; equivalent chronotropic effects were achieved with stimulation frequencies that were only about one-third of those cited above. There was a moderate, but significant, autonomic interaction: in the group of seven animals, the positive chronotropic effect of sympathetic stimulation at 1.4 Hz was 72% greater at the low level (0 Hz) than at the high level (8.4 Hz) of vagal activity.

Psychophysiological Responses of Pilots in Hypoxia Training at 7000 and 7500 m

2020 ◽  
Vol 91 (10) ◽  
pp. 785-789
Author(s):  
Dongqing Wen ◽  
Lei Tu ◽  
Guiyou Wang ◽  
Zhao Gu ◽  
Weiru Shi ◽  
...  
Keyword(s):  
Heart Rate ◽  
Psychomotor Performance ◽  
Physiological Responses ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Awareness Training ◽  
Similar Frequency ◽  
Psychophysiological Responses ◽  
The Mean ◽  
Training Protocol

INTRODUCTION: We compared the physiological responses, psychomotor performances, and hypoxia symptoms between 7000 m and 7500 m (23,000 and 24,600 ft) exposure to develop a safer hypoxia training protocol.METHODS: In altitude chamber, 66 male pilots were exposed to 7000 and 7500 m. Heart rate and arterial oxygen saturation were continuously monitored. Psychomotor performance was assessed using the computational task. The hypoxic symptoms were investigated by a questionnaire.RESULTS: The mean duration time of hypoxia was 323.0 56.5 s at 7000 m and 218.2 63.3 s at 7500 m. The 6-min hypoxia training was completed by 57.6% of the pilots and 6.1% of the pilots at 7000 m and at 7500 m, respectively. There were no significant differences in pilots heart rates and psychomotor performance between the two exposures. The Spo2 response at 7500 m was slightly severer than that at 7000 m. During the 7000 m exposure, pilots experienced almost the same symptoms and similar frequency order as those during the 7500 m exposure.CONCLUSIONS: There were concordant symptoms, psychomotor performance, and very similar physiological responses between 7000 m and 7500 m during hypoxia training. The results indicated that 7000-m hypoxia awareness training might be an alternative to 7500-m hypoxia training with lower DCS risk and longer experience time.Wen D, Tu L, Wang G, Gu Z, Shi W, Liu X. Psychophysiological responses of pilots in hypoxia training at 7000 and 7500 m. Aerosp Med Hum Perform. 2020; 91(10):785789.

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