PubMed Health⌕ Search

Biomedical subjects

M Kordas

Publications and source records attributed to M Kordas.

At least 19 recordsLinked to original sources

Analog simulation of two clinical conditions: (1) acute left ventricle failure; (2) exercise in patient with aortic stenosis.

A computer analysis of an equivalent electronic circuit is developed. Thus it is possible to simulate the human cardiovascular system, its negative feedback loops (including the control of venous tone, of myocardial contractility, and of heart rate) and negative intrathoracic pressure. If the simulated cardiovascular system is acted upon by various disturbances their consequences can be studied in detail. The consequences of two disturbances are studied by simulation: (i) acute left ventricular failure and (ii) exercise (decreased peripheral resistance) in aortic stenosis. However, prior to the simulation of the latter, a relatively complex condition, two additional procedures are implemented, i.e. simulations of (iii) increased sympathetic tone and of (iv) aortic stenosis are performed. Simulation of exercise (decreased peripheral resistance) in aortic stenosis is also compared with data observed in patients. Results show that, by using the present equivalent circuit, conditions described above can be qualitatively and to some extent quantitatively well simulated.

Acute Disease↗

Subperiosteal elevation of the ulnar nerve during internal fixation for fractures of the distal humerus assessed by intra-operative neurophysiological monitoring.

Ulnar nerve function, during and after open reduction and internal fixation of fractures of the distal humerus with subperiosteal elevation of the nerve, was assessed by intra-operative neurophysiological monitoring. Intermittent recording of the compound muscle action potentials was taken from the hypothenar muscles in 18 neurologically asymptomatic patients. The mean amplitude of the compound muscle action potential after surgery was 98.1% (sd 17.6; -37% to +25%). The amplitude improved in six patients following surgery. Despite unremarkable recordings one patient had progressive paresis. Motor impairment is unlikely if the compound muscle action potential is continuously preserved and not reduced by more than 40% at the end of surgery. Temporary decreases in amplitude by up to 70% were tolerated without clinical consequences. However, repeated clinical examination is obligatory to recognise and treat early post-operative palsy.

Action Potentials↗

Simulation of pulmonary ventilation and its control by negative feedback.

The equivalent electronic circuit developed to simulate pulmonary ventilation is upgraded to incorporate homeostasis, i.e. a negative feedback loop. The latter can be made either inactive or active. In the former condition, only the immediate consequence of a disturbance shows up. In the latter condition, however, full homeostatic--sometimes very complex--response can be studied. The effects of three types of disturbances are studied in both conditions (i.e. open loop, closed loop): increased CO2 production, temporary apnoea, and of bronchoconstriction (in the whole lung or only in part of the lung). The effect of increased CO2 production is increase in pulmonary ventilation and increase in pCO2. The latter strongly depends on the feedback response. Temporary apnoea results in a transient increase in pCO2. However, if the time constant of the feedback loop is large enough, this type of disturbance results in a maintained periodic, Cheyne-Stokes-type breathing. Bronchoconstriction in 100% of the lung results in a decrease in tidal volume. If homeostasis is active this decrease is compensated by an increase in the inspiratory effort. However, if bronchoconstriction occurs only in 50% of the lung, inspiratory effort is greatly changed through inter-alveolar elastic interactions, giving rise to the so-called pendelluft.

Computer Simulation↗

Simulation of some short-term control mechanisms in cardiovascular physiology.

The equivalent electronic circuit, developed to simulate cardiovascular physiology, is upgraded to incorporate negative feedback loops. In this way homeostasis of the arterial pressure is simulated in exercise, in haemorrhage, in the insufficiency of the aortic valve, and in hypervolemia. The results show that homeostasis supports the cardiovascular system by modulating Starling mechanism(s) in exercise, haemorrhage and hypervolemia. In aortic insufficiency it seems that only Starling mechanism(s) can maintain cardiac output and arterial pressure.

Aortic Valve Insufficiency↗

Circulatory effects of internal jugular vein compression: a computer simulation study.

The effects of compression of the internal jugular veins and the inferior vena cava are simulated using an equivalent electronic circuit, which included simulation of cardiocirculatory phenomena and special features of the cerebral circulation. Compression of the inferior vena cava resulted in a profound decrease in cardiac output (from 4.5 to 1.51min(-1)) and arterial pressure (from 140/85 to 50/35 mmHg). Compression of the internal jugular veins resulted in a negligible decrease in cardiac output and arterial pressure, with a cerebral blood flow that was slightly decreased. Cerebral capillary and internal jugular pressures were considerably increased, leading to obstruction of cerebral veins and increased pressure (from 9 to 22 mmHg) and volume (from 120 to 145 ml) of the cerebrospinal fluid (CSF). Increased cerebral capsule compliance resulted in decreased CSF pressure (from 9 to 8.5 mmHg), but CSF volume increased (from 120 to 190 ml). A small increase in brain volume (from 1,000 ml to 1,060 ml, 6% volume increase) was compensated for by an equal decrease in the volume of CSF. When brain volume was above 1,080 ml, the absorption of CSF was reduced, and its pressure increased.

Cerebrovascular Circulation↗

Simulation of cardiovascular physiology: the diastolic function(s) of the heart.

The cardiovascular system was simulated by using an equivalent electronic circuit. Four sets of simulations were performed. The basic variables investigated were cardiac output and stroke volume. They were studied as functions (i) of right ventricular capacitance and negative intrathoracic pressure; (ii) of left ventricular relaxation and of heart rate; and (iii) of left ventricle failure. It seems that a satisfactory simulation of systolic and diastolic functions of the heart is possible. Presented simulations improve our understanding of the role of the capacitance of both ventricles and of the diastolic relaxation in cardiovascular physiology.

Cardiac Output↗

Cardiovascular physiology: simulation of steady state and transient phenomena by using the equivalent electronic circuit.

By using commercially available software it is readily possible to design electronic circuits and to analyze them. By introducing the concept of equivalent quantities a simulation of various physiological phenomena is possible. This includes the steady state as well as various complex transient phenomena. This paper describes the use of an equivalent electronic circuit in simulating the cardiovascular system. It allows a stepwise upgrading. The first step is a one-ventricle circuit similar to the Starling heart-lung preparation. The final step is an equivalent circuit allowing simulation of various normal as well as pathological states (e.g. effects of heart rate, negative intrathoracic pressure, exercise, hemorrhage, heart failure, and hypertension). The degree of disturbance can be set by adjusting the value of single components. Following this, the optimal type of compensation (e.g. the increase in blood volume in failure of the right ventricle; systemic venoconstriction in failure of the left ventricle) of the basic disturbance can be searched for, activated and the consequences studied. The described approach has been found a useful tool in teaching physiology and pathophysiology for postgraduate medical students.

Cardiovascular Physiological Phenomena↗

[History of medicine in educating physicians].

Basing on questionnaire studies, which covered 149 students of various medical faculties, the author has analysed a significance of the history of medicine in creating the attitudes of future physicians and a level of the interest in subject. In conclusions she has indicated a need of changing from informative classes to problem discussions and a necessity to use various forms including the visual ones, to carry teaching classes.

Education, Medical, Undergraduate↗

The separation of exocytosis from endocytosis in rat melanotroph membrane capacitance records.

1. Using the patch-clamp technique, we have monitored the secretory activity of single rat melanotrophs. Changes in membrane capacitance (Cm) were measured to detect small discrete femtofarad steps. These are believed to be due to interactions between single secretory organelles (granules) and plasmalemma. 2. A new approach was introduced to measure the amplitude of discrete steps in Cm. Records of Cm were converted into time derivatives, where discrete steps appeared as transients. A transient due to a 2 fF discrete step in Cm was easily distinguished from random noise, since the probability of such a transient being due to random noise was less than 0.01. To distinguish apparent steps from noise the computer-based analysis employed a threshold of 3 times the standard deviation of the noise time derivative (dCm/dt). A phase diagram was created by plotting dCm/dt versus Cm, from which the magnitude and direction of transients were determined. Transients due to 2 fF steps (equivalent to a signal-to-noise ratio of 1) were detected with a reliability of 100%, whereas steps of 1 fF were detected with a reliability of more than 60%. The amplitude of false steps detected by the program was less than 1 fF, and the frequency of false detections of 0.075 S-1 was equal for exocytotic and endocytotic events. 3. Electron microscopy was used to measure secretory organelle size and an immunogold technique was used to label the electron micrographs with an anti-adrenocorticotrophin (ACTH) antibody. Secretory organelles in cultured and non-cultured cells were of similar diameter. All sizes of secretory granules appear to contain ACTH, since secretory organelles of similar diameter stained positively with the anti-ACTH antibodies. 4. Small discrete steps in Cm, recorded with the whole-cell configuration and loosely buffered cytosolic calcium, were similar to the estimated Cm of secretory organelles from morphological data. Thus, measured discrete steps in Cm reflect interactions between single organelle size and plasma membrane. Exocytotic and endocytotic steps were found to be of similar size. 5. To separate exocytosis from endocytosis in Cm records, we assumed that the rates of exocytosis and endocytosis were related to the respective frequencies of discrete steps in Cm. A relationship between the frequency of exocytotic, but not endocytotic events, and the rate of change in Cm was observed. Thus, under our experimental conditions, an increase in Cm could be explained by an increased rate of exocytosis in rat melanotrophs.

Animals↗

Effects of irreversible and reversible cholinesterase inhibitors on single acetylcholine-activated channels.

The use of cholinesterase (CHE) inhibitors provided valuable information about the mechanism(s) of neuromuscular transmission, but questions on side effects at the level of ACh-activated channels were raised. Patch-clamp recording was used to study the effects of prostigmine (PST) and methanesulfonyl fluoride (MSF), a reversible and an irreversible cholinesterase inhibitor, respectively, on ACh-activated channels. We found that these drugs diminish the average dwell time of elementary currents from around 5 msec (control) to less than 1 msec in the presence of PST (20 microM) or MSF (5 mM) (at room temperature). With MSF the ACh-activated channel conductance of the most frequently observed amplitude class decreased from 45 pS (control) to 30 pS, but not in the presence of PST. In control conditions there were also amplitude classes of 60 and 24 pS, with probabilities of occurrence less than 10%. In the presence of 1.5 mM MSF, where current dwell time was not affected, additional subconductance states of 19 and 36 pS were observed and may be due to partial blockade of the open channel. We conclude that the drug of choice to be used in studies on the role of CHE in the neuromuscular transmission is MSF, because at 20 microM PST, where blockade of ACh-activated channels is significant, cholinesterase was reported to be partially inhibited, whereas at 1 mM MSF it is fully inhibited and the dwell time of ACh-activated channels is not affected.

Acetylcholine↗

The voltage-clamp apparatus assisted by a 'current pump'.

A current pump is described, which is attached to the last stage of the 2-microelectrode voltage-clamp apparatus. Thus a voltage-to-current conversion independent of the impedance of the current microelectrode is obtained. In this way it is possible to pass relatively large currents through the current microelectrode and in the same time to have a stable negative feed-back system.

Animals↗

The voltage and temperature dependence of the end-plate current in frog skeletal muscle.

The effect of membrane potential (V) on the half-time (t 1/2) of the falling phase of the end-plate current (e.p.c.) was found to obey the equation t 1/2 = A X eBV + C, where A, B and C are constants. The temperature dependence of t 1/2 was found to follow the Arrhenius equation. The activation energy (Ea) varied from about 50 kJ/mol to about 120 kJ/mol. At membrane potentials between about -40 mV and -140 mV, the Ea/V relation was similar in all end-plates investigated: Ea increased if membrane potential was made more negative. At membrane potentials between about +60 mV and -40 mV, however, the Ea/V relation was different in different end-plates: If membrane potential was made more negative, Ea was either increased, or not affected, or decreased. It is concluded that at negative levels of membrane potential the decay of the e.p.c. depends on average life-time of ionic channels, opened up by the action of acetylcholine on junctional receptors. At strongly positive levels of membrane potential, however, the decay of the e.p.c. can be determined by the average life-time of ionic channels or by the clearance of transmitter from the synaptic cleft, or both. Either of these processes can be reflected in the value of constant C in the above equation.

Animals↗

The effect of papaine on the time course of the end-plate current.

Papaine is known to detach cholinesterases from the synaptic cleft. It could be expected that this would result in an increase of the amplitude and half-time of the end-plate current. Thus, the effect of papaine on the end-plate current. Thus, the effect of papaine on the end-plate current should be similar to the effect of anticholinesterase methanesulfonylfluoride. The end-plate current was recorded in frog skeletal muscle at various levels of membrane potential, before and after papaine was added to the bath. The effect of papaine was an increase of the half-time of the end-plate current, similarly as after treatment of the muscle by methanesulfonylfluoride. It seems that both papaine and methanesulfonylfluoride have a similar mechanism of action. In either experimental condition hydrolysis of transmitter is decreased or abolished, which results in an increase of the half-time of the end-plate current.

Action Potentials↗

On the role of junctional cholinesterase in determining the time course of the end-plate current.

1. The effect of membrane potential on the half-time (t1/2) of the falling phase of the end-plate current was studied both in the absence and the presence of anticholinesterase. 2. In absence of anticholinesterase the relation between log t1/2 and membrane potential was linear at negative, and not linear at positive levels of membrane potential. This relation was not affected by the quantity of the released transmitter. 3. In presence of an irreversible anticholinesterase the relation between log t1/2 and membrane potential was shifted towards higher values of log t1/2. This shift could be counteracted by decreasing the quantity of the released transmitter. 4. It is concluded that in presence of anticholinesterase the decay of the end-plate current is slowed down because in this experimental condition the elimination of transmitter from the synaptic cleft is slowed down. 5. These observations were made in muscles bathed in Tris-HCl buffered Ringer solution. If a phosphate buffered Ringer solution was used, the relation between log t1/2 and membrane potential was linear throughout the range of membrane potentials studied. The reason why different buffers give different results is not clear and should be further studied.

Animals↗