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Biomedical subjects

R H Morton

Publications and source records attributed to R H Morton.

At least 37 records · Page 2Linked to original sources

Low quantal content of the endplate potential reduces safety factor for neuromuscular transmission in the diaphragm of the newborn rat.

We have used phrenic nerve-hemidiaphragm preparations from rats aged 11-28 days to determine the electrophysiological basis of the three-fold increase in sensitivity of the neonatal neuromuscular junction to non-depolarizing neuromuscular blocking drugs. The mean resting membrane potential (RMP) of intact muscle fibres at 19-21 degrees C increased from -67.1 (SEM 0.6) mV at 11 days to -75.8 (0.06) mV at 28 days. Over the same age range the mean size of miniature endplate potentials (MEPP) decreased from 1.7 (0.1) mV to 1.4 (0.03) mV, and the threshold depolarization to produce a muscle action potential increased from 6.8 (0.4) mV to 9.5 (0.6) mV. The quantal content of the evoked endplate potential (EPP) calculated from EPP and MEPP measured in cut muscle fibres was only 6.6 (0.9) at 11 days, but this increased to 21.1 (2.3) at 21 days. As a result of the low quantal content of the EPP, the safety factor for neuromuscular transmission was only 1.7 at 11 days, compared with 2.8 at 20 days. A safety factor of 1.7 in the youngest rats indicates that block of only about 40% of postjunctional acetylcholine receptors would result in failure of neuromuscular transmission. Hence, a low quantal content of EPP, leading to a low safety factor for neuromuscular transmission, probably underlies the increased sensitivity to non-depolarizing neuromuscular blocking drugs of young rats and, by inference, human neonates.

Action Potentials↗

Comment on 'ventilation and blood lactate increase exponentially during incremental exercise'.

A recent paper in this journal has examined the ventilatory compensation for metabolic acidosis with increasing oxygen uptake, making extensive use of mathematical and statistical techniques. The authors conclude that '...respiratory compensation for metabolic acidosis during incremental exercise is a continuous process...'. While this may indeed be so, the following major aspects of the paper render the evidence at best dubious, surely inconclusive and perhaps even worthless: (1) The mathematical and statistical methodology is sloppy, incomplete and, at times, flawed. (2) No discontinuous model is presented for comparative purposes, only three continuous ones. (3) The authors ignore the fact that some threshold models produce smooth continuous data, and as a consequence, a good fit of a smooth continuous model cannot exclude the presence of a threshold. (4) The data in Table 5 show the amplitude parameter A of the preferred model to be not significantly different from zero. This paper draws these matters to the attention of readers of this journal, reviewers of manuscripts and other researchers, with comment and suggestion. This is done in the hope that all those concerned with mathematical and statistical methodologies will become more aware of their proper use.

Anaerobic Threshold↗

Age-dependent variation in response to tubocurarine in the isolated rat diaphragm.

The EC50 of tubocurarine was determined in phrenic nerve-hemidiaphragm preparations obtained from 35 Sprague-Dawley rats aged 0-46 days. We measured also the ratio of the fourth to the first twitch in the train-of-four (T4:T1) when the first twitch of the train was depressed to 50% of control. The preparation was not unduly sensitive to tubocurarine at 0 days and there was little evidence of T4:T1 fade. However, by age 11 days the preparation exhibited fade and a three-fold sensitivity to tubocurarine similar to that in the human neonate. We conclude that the phrenic nerve-hemidiaphragm preparation from 11-day-old rats should be a suitable model in which to investigate the biochemical and electrophysiological basis of the sensitivity seen in humans.

Age Factors↗

Elevated serum enzyme activity: an explanation-based model.

The well-documented pattern of elevated serum enzyme activity (ESEA) data after a single bout of unaccustomed exercise can very easily be modeled using a biexponential curve. However, the changed pattern of ESEA after a second exercise bout, or after a period of conditioning or during repetitive training, demonstrates that exercise-induced adaptations have been taking place. The mechanism for this is unclear. One plausible explanatory hypothesis is that within the pool of muscle fibers, some fibers are stress susceptible or weak, and the pool becomes diminished as a result of damage induced by earlier exercise. Repair of the muscle damage takes place during the period after exercise but may be incomplete at the time of a subsequent exercise bout, in which case ESEA amplitude is reduced. Frequently repeated bouts may lead to chronic ESEA. These ideas are developed, both mathematically and graphically, by means of a compartment model approach. In so doing, the model explains documented patterns of ESEA response to single and multiple exercise bouts, both closely and widely spaced. Predictions are possible using the model, in particular the previously unreported baseline overshoot (reduction below resting levels) in serum enzyme activity occurring beyond 82 h after very severe exercise. Some directions for experimentation to test the validity of the model are suggested.

Creatine Kinase↗

Dose/response effects of exercise modeled from training: physical and biochemical measures.

This study has measured the pattern of elevated serum enzyme activity (ESEA) during extended daily training in a dose-response manner and compared ESEA to the pattern of accumulated fitness and fatigue predicted from a mathematical model previously described. Blood samples were taken regularly during the study from each subject and the activity of lactate dehydrogenase (LDH), creatine kinase (CK), and aspartate aminotransferase (AST) in the serum was measured. Although no single physiological/biochemical correlate of the hypothesized fatigue compartment of performance is firmly identified it is significant that the pattern of variation of model fatigue and ESEA throughout training were similar although slightly out of phase. With continued hard training, model fatigue began to plateau and concomitantly ESEA declined exponentially from its initial high value in early training. During relative rest throughout a tapering period following training both ESEA and fatigue reverted quickly towards baseline and follow the similar but earlier time course in blood of a degradative membrane enzyme phospholipase A2 observed in clinical studies.

Adult↗

The clearance rate of exercise-elevated blood lactate following physical training.

In this paper, previous studies regarding the effect of physical training on the disappearance rate of blood La during recovery after strenuous exercise have been briefly summarized. The results of our own recent study of this problem have also been added. It may be concluded that there is some evidence for an improved lactate metabolic clearance rate resulting from physical training in human subjects, when the degradation rate is estimated from serial blood samples taken during a standard ramp ergometer test to exhaustion during each week of a training/detraining sequence. This beneficial effect of training, however, may also be influenced by the initial physical status of the subject and the nature of the training program.

Exercise↗

Optimizing athletic performance by influence curves.

Recent application of modeling techniques to physical training has opened the possibility for prediction from training. Solution of the inverse problem, determining a training program to produce a desired performance at a specific time, is also possible and may yield strategies for achieving better training and tapering (complete or relative rest for a period before competition) regimens for competitive athletes. A mathematical technique derived from model theory is described in this paper that allows the design of an optimal strategy of physical preparation for an individual to do well in a single future competitive event or cluster of events. Simulation results, using default parameters of a training model, suggest that presently accepted forms of taper for competition may remain too rigorous and short in duration to achieve the best result possible from the training undertaken.

Humans↗

Modelling human power and endurance.

A generalised three component hydraulic model has been proposed to represent the human bioenergetic processes relating internal energy stores to performance during exercise, and into recovery. Further development of the model allows testable predictions to be made. In particular in this paper I examine certain hypotheses of chemical fuel shortage as a subgroup of the potential causes of fatigue, and their implications for maximal power and for endurance. The assumption that the limitation to sustainable power is direct proportionality to the glycogen store remaining, appears the most feasible. Based on this assumption, equations for the decline in maximum attainable power over time, the endurance at fixed workrates and the endurance at incremental tests (as a function of the increment slope) are obtained. Using published data for fit males, the maximum exertable power declines after about 6 s at 972 W to very low levels after about 2 min. For constant powers selected between 208 and 927 W, endurance declines from ad infinitum to only 6 s. Endurance at VO2max is predicted to be about 9 min. For incremental exercise tests of slope ranging from 30 W/min to 60 W/min, endurance lessens from 14 to 9 min. In these tests the anaerobic threshold is reached in times between 6 and 3 min. Although the power at termination of a test increases with incremental slope, terminal oxygen consumption is effectively constant. Almost all these model predictions are observed to correspond well with published experimental findings. These results suggest that the model can be used to represent an adequate overview of the operation of the human bioenergetic system.

Adenosine Triphosphate↗

Modeling human performance in running.

This paper focuses on the characteristics of a model interpreting the effect of training on athletic performance. The model theory is presented both mathematically and graphically. In the model, a systematically quantified impulse of training produces dual responses: fitness and fatigue. In the absence of training, both decay exponentially with time. With repetitive training, these responses satisfy individual recurrence equations. Fitness and fatigue are combined in a simple linear difference equation to predict performance levels appropriate to the intensity of training being undertaken. Significant observed correlation of model-predicted performance with a measure of actual performance during both training and tapering provides validation of the model for athletes and nonathletes alike. This enables specific model parameters to be estimated and can be used to optimize future training regimens for any individual.

Adult↗

Effects of halothane on arrhythmias induced by myocardial ischaemia.

The effect of halothane on arrhythmias induced by ischaemia was investigated in rats, isolated perfused rat hearts, and pigs. Responses to the occlusion of the left anterior descending coronary artery were determined in groups (n = 9) of chronically prepared rats treated with no halothane, 0.5, or 1.0 per cent halothane immediately after occlusion; in isolated rat hearts (n = 10) treated with no halothane, 0.5, 1.0, 2.0, or 4.0 per cent halothane for 15 min before and after occlusion; and 20-25 kg pigs (n = 11) anaesthetised with halothane or pentobarbital. The ECG, arrhythmias, blood pressure (BP), heart rate (HR) and extent of infarction were determined in each model. In pigs, left ventricular pressure, dp/dtmax and cardiac output were also measured. In chronically prepared rats, halothane anaesthesia started after occlusion was antiarrhythmic and decreased the incidence of ventricular fibrillation and resulting mortality. In isolated rat hearts, 0.5 or 1.0 per cent halothane had little effect on occlusion-induced arrhythmias. The highest concentration of halothane increased the incidence of ventricular fibrillation both before and after occlusion. Halothane decreased developed ventricular pressure in a dose-dependent manner. In acutely prepared pigs, halothane pre-treatment had no appreciable effect upon occlusion-induced arrhythmias when compared with pentobarbital anaesthesia. Thus, halothane is antiarrhythmic when treatment is initiated after occlusion in the rat but this action is not seen in isolated hearts or intact pigs. The antiarrhythmic action of halothane is, therefore, species and model dependent.

Animals↗

Detection of a lactate threshold during incremental exercise?

An important question in the study of the exercise response is the real or imaginary nature of the anaerobic threshold, and mathematical modeling techniques have been invoked to assist in resolving this issue. Two opposing views with competing data models recently published in this journal are criticized. One view suggests a segmented model with a discontinuous first derivative at the threshold. The other suggests a continuous model over the whole work load range, implying the anaerobic threshold to be imaginary. However, neither group of authors has devoted proper rigorous attention to the models they use. Had this been done, some of the divergence of opinion may have been avoided. Ideal data from an alternate segmented model that has a continuous first derivative at the threshold are considered for comparative purposes. This suggests that the log-log transformation method may well lead to improved detection of a threshold when one exists, although the estimates of the threshold value obtained are unreliable. Modeling methodology is a useful approach to the resolution of scientific issues, but there exist fundamental implications and alternatives that must be fully recognized.

Anaerobic Threshold↗

A systems model approach to the ventilatory anaerobic threshold.

An analogue systems model of whole-body human bioenergetics predicts a change in kinetics of VO2 time series values as a result of exercise levels above an anaerobic threshold. Plotted VO2 results from exercising subjects appear to confirm this change. The purpose of this study is to describe the background to the systems model analogue of the anaerobic threshold and a test procedure devised to estimate this threshold. The estimate so obtained has the dual advantages of being based on model theory and of not being subject to the sort of ambient variations inherent in a single-test determination. A non-homogeneous group of eight subjects comprising a full replicate of a 2(3) factorial experimental design, with factors age, sex and training status, took part in the study. On one hand the results indicate acceptance of the systems model theory. On the other, the analogue threshold measure possesses corresponding properties to the conventional anaerobic threshold. It is higher for trained (155-214 W) than for untrained subjects (108-158 W), higher for males (149-214 W) than for females (108-170 W), and displays no evident interaction effects. Results for the VO2 time constant and for the work efficiency, display similar effects except for an interaction in the latter between age and training status. These experimental findings are regarded as confirmatory of the nature of the analogue threshold measure.

Adult↗

A simple model to link hemodynamics, fatigue and endurance in static work.

This paper combines assumptions on blood flow changes during static work, on fatigue resulting from a shortage of chemical fuel, and on energy supply and demand considerations, to construct a systems model for endurance time in the maintenance of isometric muscle tension. All these quantitative assumptions are based on published experimental findings. The model is applied to published data on isometric endurance and a fit yielding R2 = 0.98 obtained on a composite data set.

Energy Metabolism↗

Delayed or accelerated oxygen uptake kinetics in the transition from prior exercise?

Reported experimental findings are at variance with each other on the question as to whether O2 uptake (VO2) kinetics are delayed, advanced, or remain unaltered in the transition from prior exercise. Critical examination of these studies tend to suggest that not a great deal of reliance can be placed on their evidence in attempting to resolve the question. They seem to display a disregard for the theoretical properties of the VO2 kinetic model used; in some cases incorrect statistical inferences appear to have been made; most are mathematically incomplete; and the experimental designs have not been appropriately chosen so as to examine the whole question of altered VO2 kinetics. These points are detailed and discussed so that future designed experiments obtain sufficient reliable evidence with which to resolve the question.

Kinetics↗

On a model of human bioenergetics. II. Maximal power and endurance.

The properties of a proposed three component hydraulic model of human bioenergetics are examined in respect of the maximum exertable power and the endurance time for given workloads. An equation expressing the decline in maximal effort during an "all-out" exercise is derived, from which a VO2 time equation can be deduced. In addition a workload versus endurance time equation can be obtained, enabling the prediction of time to exhaustion. The resulting equations are illustrated graphically by means of a numerical example. Model predictions, when compared with experimental results, reveal discrepancies which confirm the rejection of the model, as was suggested in an earlier paper.

Energy Metabolism↗

A three component model of human bioenergetics.

The model described in this article is a generalised three component hydraulic model, proposed to represent net whole body bioenergetic processes during human exercise and recovery. During exercise, fluid flows from the three interconnected vessels in the system represent the breakdown of high energy phosphates (phosphagens), oxygen consumption and lactic acid production. During recovery, replenishment of the fluids represents the repayment of oxygen debt. The model is quantified and solved mathematically, and the solution compared with observed experimental data. Since currently known physiological facts are consistent with four configurations of this model, further experimentation is necessary.

Energy Metabolism↗