PubMed Health⌕ Search

Biomedical subjects

Anton Amann

Publications and source records attributed to Anton Amann.

13 recordsLinked to original sources
PubMed2006

Modeling of twitch fade based on slow interaction of nondepolarizing muscle relaxants with the presynaptic receptors.

Nondepolarizing muscle relaxants (MRs) diminish the indirectly evoked single twitch due to their binding to the postsynaptic receptors. Additionally, the MRs produce progressive diminution of successive twitches upon repetitive stimulation (fade). Our study addresses the generation of fade as observed under clinical situation. The study was conducted in two phases. In the clinical part, we have evaluated the time course of twitch depression and fade following the administration of several doses of three MRs (rocuronium, pancuronium, and cisatracurium). In the second part, we have modified our model of neuromuscular transmission to simulate the time course of twitch depression and fade. The MR was assumed to bind to a single site on the presynaptic receptor to produce fade. The rates of interaction with the presynaptic receptors were characterized in terms of the arbitrarily assigned equilibrium dissociation constant and the half-life for dissociation of the presynaptic complex. A method was developed to relate the release of acetylcholine to the occupancy of the presynaptic receptors. The strength of the first and the fourth twitch was calculated from the peak concentration of the activated postsynaptic receptors, i.e., of those receptors with both sites occupied by acetylcholine. Our results indicate that, while the affinity of the MR for the presynaptic receptor plays little role in the time course of fade, the rate of dissociation of the complex between the presynaptic receptors and the muscle relaxant may be critical in determining the time course of fade. Tentative estimates of this parameter are offered.

Acetylcholine↗
PubMed2006

Altered electrical activity of fibrillation process following thrombolytic therapy in out-of-hospital cardiac arrest patients with sustained ventricular fibrillation.

The likelihood of successful defibrillation in patients with sustained ventricular fibrillation (VF) is increased after administering thrombolytics during cardiopulmonary resuscitation (CPR). While dissolution of coronary artery thrombosis resolves the underlying cause of myocardial infarction in the majority of patients, improved microcirculatory reperfusion and alteration of the electrical activity of the fibrillation process may increase the likelihood of restoring spontaneous circulation in cardiac arrest patients. Electrocardiography is a sensitive means of displaying current myocardial perfusion in VF using changes in the frequency and amplitude of fibrillation. Our hypothesis postulates that thrombolytic therapy during CPR increases fibrillation frequency, fibrillation amplitude and amplitude spectrum area, thus improving ventricular fibrillation status and the chance of successful defibrillation.

Cardiopulmonary Resuscitation↗
PubMed2005

Reliability of old and new ventricular fibrillation detection algorithms for automated external defibrillators.

BACKGROUND: A pivotal component in automated external defibrillators (AEDs) is the detection of ventricular fibrillation by means of appropriate detection algorithms. In scientific literature there exists a wide variety of methods and ideas for handling this task. These algorithms should have a high detection quality, be easily implementable, and work in real time in an AED. Testing of these algorithms should be done by using a large amount of annotated data under equal conditions. METHODS: For our investigation we simulated a continuous analysis by selecting the data in steps of one second without any preselection. We used the complete BIH-MIT arrhythmia database, the CU database, and the files 7001-8210 of the AHA database. All algorithms were tested under equal conditions. RESULTS: For 5 well-known standard and 5 new ventricular fibrillation detection algorithms we calculated the sensitivity, specificity, and the area under their receiver operating characteristic. In addition, two QRS detection algorithms were included. These results are based on approximately 330,000 decisions (per algorithm). CONCLUSION: Our values for sensitivity and specificity differ from earlier investigations since we used no preselection. The best algorithm is a new one, presented here for the first time.

Algorithms↗
PubMed2005

Volume of the effect compartment in simulations of neuromuscular block.

BACKGROUND: The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants. METHODS: The molar amount of the postsynaptic receptors at the motor end plates in muscle was assumed constant; the apparent receptor concentration in the effect compartment is the ratio of this amount and the volume arbitrarily assigned to the effect compartment. The muscle relaxants were postulated to diffuse between the central and the effect compartment and to bind to the postsynaptic receptors. NMB was calculated from the free concentration of the muscle relaxant in the effect compartment. RESULTS: The simulations suggest that the time profiles of NMB and the derived pharmacokinetic and pharmacodynamic variables are dependent on the apparent receptor concentration in the effect compartment. For small, but not for large, volumes, times to peak submaximal NMB are projected to depend on the magnitude of NMB and on the binding affinities. CONCLUSION: An experimental design to estimate the volume of the effect compartment is suggested.

Animals↗
PubMed2005

Myasthenia gravis and myasthenic syndrome: simulation of twitch strength with or without therapy.

To examine the quantitative relationship between indirectly evoked twitch and decreases in the number of either postsynaptic receptors or acetylcholine molecules released by a single stimulus, we studied these variables in a computer-simulated model of neuromuscular transmission. Twitch strength decreased if the number of receptors decreased to below 30% of normal or the number of acetylcholine molecules released by a stimulus decreased to below 80%. Inhibition of acetylcholine hydrolysis to 50% restored twitch strength in the presence of a decreased number of receptors. However, twitch strength was more easily restored to normalcy by augmenting the release of acetylcholine, if the release was diminished by disease. The simulations mimic the clinically known therapeutic outcomes in certain disorders of neuromuscular transmission. These results provide useful quantitative insights into the relationship between acetylcholine receptors or the stimulus-induced release of acetylcholine and muscle function in myasthenia gravis or Lambert-Eaton myasthenic syndrome.

Acetylcholine↗
PubMed2004

Comparison of the dissolution of metaxalone tablets (Skelaxin) using USP Apparatus 2 and 3.

The purpose of this study was to evaluate the effect of pH on the dissolution behavior of metaxalone in the marketed product Skelaxin tablets. The dissolution was evaluated using United States Pharmacopeia (USP) dissolution Apparatus 2 and 3 at pHs ranging from 1.5 to 7.4. Results from these studies show that the dissolution of this product is pH dependent. At low pH (simulated gastric fluid, pH 1.5), the dissolution of metaxalone from Skelaxin tablets was less than 10% over 75 minutes; whereas, dissolution at pH 4.5 showed greater than 90% release in the same time period. These results were consistent for both Apparatus 2 and 3. This suggests that Skelaxin Tablets should be considered a delayed release dosage form.

Delayed-Action Preparations↗
PubMed2004

Simulation of interaction between two non-depolarizing muscle relaxants: generation of an additive or a supra-additive neuromuscular block.

GOAL: To examine in a model of neuromuscular transmission the interaction between two non-depolarizing muscle relaxants. An additive or a supra-additive interaction was evaluated as a function of the affinities of acetylcholine and the muscle relaxants for the two binding sites at a single receptor. METHODS: Affinity of acetylcholine for site1 was postulated to be higher than for site2. Muscle relaxants may display a similar pattern of affinities, a higher affinity for site2, or the affinities may be identical. Receptors with both sites occupied by acetylcholine are activated and, if their concentration at an end plate surpasses the critical threshold, initiate contraction of the associated muscle fiber. The number of contracting muscle fibers determines twitch strength of the whole muscle. Neuromuscular block (NMB) = 1--twitch. NMB was simulated for muscle relaxants acting as single agents or in three types of combinations. (a) Complementary fractions of equieffective concentrations. (b) Variable combinations of equieffective concentrations producing NMB equal to NMB produced by the single muscle relaxant (isobolographic analysis), and (c) NMB-vs.-concentration relationship of single agents and of their combination in a fixed ratio. RESULTS: Additive interaction was simulated for pairs of muscle relaxants displaying identical ratios of affinities. All other pairs produce a supra-additive interaction, more prominent, the more divergent the patterns of affinities. The slopes of NMB-vs.-concentration curves were steeper for supra-additive combinations than for single agents. CONCLUSION: The simulations define conditions leading to additive or supra-additive interaction and suggest an experimental design suitable to test the results.

Acetylcholine↗
PubMed2003

Competition between acetylcholine and a nondepolarizing muscle relaxant for binding to the postsynaptic receptors at the motor end plate: simulation of twitch strength and neuromuscular block.

UNLABELLED: The goal of the study was to simulate twitch strength and neuromuscular block produced by nondepolarizing muscle relaxants. METHODS: In the proposed model, affinities of the two binding sites at a single postsynaptic receptor for acetylcholine (A) and the muscle relaxant (D) define the formation of three complexes with A only, three complexes with D only, and two complexes with both A and D. Twitch strength was postulated to be a function of the receptors with both binding sites occupied by A, and two constants. Neuromuscular block (NMB) was calculated from NMB = 1-twitch. RESULTS: Stimulus-induced release of A results in rapid, but transient, changes in the concentrations of free A, the eight complexes, and the unoccupied receptors. Muscle relaxants that display either a congruous or an inverse pattern of affinities for the binding sites relative to those of A produce NMB vs. [D] curves with slightly different slopes but markedly different estimates for IC50. Depending on the number of activated receptors at the end plates of muscle fibers, the simulations represent the distributions of contracting fibers in a whole muscle. CONCLUSION: Simulations of competition between A and D for binding to two sites at a receptor reveal that the potencies of muscle relaxants, defined by IC50, and the slopes of the NMB vs. [D] curves depend on (1) the affinities of D for the two binding sites, (2) the orientation of the affinities relative to those of A, and (3) the affinities of A for the same two sites.

Acetylcholine↗
PubMed2003

The effects of nifedipine on ventricular fibrillation mean frequency in a porcine model of prolonged cardiopulmonary resuscitation.

UNLABELLED: We assessed the effects of a calcium channel blocker versus saline placebo on ventricular fibrillation mean frequency and hemodynamic variables during prolonged cardiopulmonary resuscitation (CPR). Before cardiac arrest, 10 animals were randomly assigned to receive either nifedipine (0.64 mg/kg; n = 5) or saline placebo (n = 5) over 10 min. Immediately after drug administration, ventricular fibrillation was induced. After 4 min of cardiac arrest and 18 min of basic life support CPR, defibrillation was attempted. Ninety seconds after the induction of cardiac arrest, ventricular fibrillation mean frequency was significantly (P < 0.01) increased in nifedipine versus placebo pigs (mean +/- SD: 12.4 +/- 2.1 Hz versus 8 +/- 0.7 Hz). From 2 to 18.5 min after the induction of cardiac arrest, no differences in ventricular fibrillation mean frequency were detected between groups. Before defibrillation, ventricular fibrillation mean frequency was significantly (P < 0.05) increased in nifedipine versus placebo animals (9.7 +/- 1.2 Hz versus 7.1 +/- 1.3 Hz). Coronary perfusion pressure was significantly lower in the nifedipine than in the placebo group from the induction of ventricular fibrillation to 11.5 min of cardiac arrest; no animal had a return of spontaneous circulation after defibrillation. In conclusion, nifedipine, but not saline placebo, prevented a rapid decrease of ventricular fibrillation mean frequency after the induction of cardiac arrest and maintained ventricular fibrillation mean frequency at approximately 10 Hz during prolonged CPR; this was nevertheless associated with no defibrillation success. IMPLICATIONS: This study evaluates the effects of a calcium channel blocker on ventricular fibrillation mean frequency, hemodynamic variables, and resuscitability during prolonged cardiopulmonary resuscitation (CPR) in pigs. Nifedipine, but not saline placebo, prevented a rapid decrease of ventricular fibrillation mean frequency after the induction of cardiac arrest and maintained ventricular fibrillation mean frequency at approximately 10 Hz during prolonged CPR but did not improve resuscitability.

Animals↗
PubMed2002

Physiologic-pharmacologic interpretation of the constants in the Hill equation for neuromuscular block: a hypothesis.

Neuromuscular block (NMB) is simulated in pharmacodynamic models using the concentration of a muscle relaxant (MR) in the effect compartment and two constants, gamma and IC50. No physiologic or pharmacologic interpretation is offered for either constant. We desired to explore whether the constants are properties of the muscle or the MR and to simulate NMB when the MR binds to two sites at a single receptor. Based on steady state conditions, we defined receptor occupancy using the equilibrium dissociation constants. Two concepts are introduced: threshold occupancy and occupancy at half-maximal NMB, Occ(NMB50). Threshold occupancy is defined as receptor occupancy at the motor end plate of a muscle fiber when the fiber fails to contract and Occ(NMB50) as the median threshold occupancy. NMB may be simulated as a function of either the concentration of the muscle relaxant or receptor occupancy. We suggest: (1) The distribution of threshold occupancies is an intrinsic property of a muscle and is characterized by two constants (gamma(o) and Occ(NMB50)); (2) gamma(o) is numerically equal to the slope of the NMB vs. concentration curves and is independent of the equilibrium dissociation constants. IC50 is code termined by Occ(NMB50) and by the equilibrium dissociation constants. (3) Binding of a muscle relaxant to the second binding site influences only the estimate of IC50 but not gamma.

Binding Sites↗
PubMed2002

The prediction of defibrillation outcome using a new combination of mean frequency and amplitude in porcine models of cardiac arrest.

UNLABELLED: We estimated the predictive power with respect to defibrillation outcome of ventricular fibrillation (VF) mean frequency (FREQ), mean peak-to-trough amplitude (AMPL), and their combination. We examined VF electrocardiogram signals of 64 pigs from 4 different cardiac arrest models with different durations of untreated VF, different durations of cardiopulmonary resuscitation, and use of different drugs (epinephrine, vasopressin, N-nitro-L-arginine methyl ester, or saline placebo). The frequency domain was restricted to the range from 4.33 to 30 Hz. In the 10-s epoch between 20 and 10 s before the first defibrillation shock, FREQ and AMPL were estimated. We introduced the survival index (SI; 0.68 Hz(-1). FREQ + 12.69 mV(-1). AMPL) by use of multiple logistic regression. Kruskal-Wallis nonparametric one-way analysis was used to analyze the different porcine models for significant difference. The variables FREQ, AMPL, and SI were compared with defibrillation outcome by means of univariate logistic regression and receiver operating characteristic curves. SI increased predictive power compared with AMPL or FREQ alone, resulting in 89% sensitivity and 86% specificity. The probabilities of predicting defibrillation outcome for FREQ, AMPL, and SI were 0.85, 0.89 and 0.90, respectively. FREQ, AMPL, and SI values were not sensitive in regard to the four different cardiac arrest models but were significantly different for vasopressin and epinephrine animals. IMPLICATIONS: We present a retrospective data analysis to evaluate the predictive power of different ventricular fibrillation electrocardiogram variables in pigs with respect to defibrillation outcome. We showed that our combination of variables leads to an improved forecast, which may help to reduce harmful unsuccessful defibrillation attempts.

Algorithms↗