Marjan Kordas

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.

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.

The effects of pH on the conductance change evoked by iontophoresis in the frog neuromuscular junction

SummaryThe amplitude of the electrophoretically evoked end-plate potential increases with changing the pH of the bathing solution from 9.4 to 5.4 at room temperature. This change is not observed at lower temperature. The underlying current (e.p.c.I) is slightly decreasing at room temperature by lowering the pH. The relationship between the amplitude of the e.p.c.I and membrane potential is highly non-linear at pH 9.4, while it is quite linear at pH 5.4. The time course of the e.p.c.I is changed neither by different pH, nor by different membrane potential. The data suggest that during the e.p.c.I, the mediator (ACh), the receptor (R) and the mediator-receptor complex are in equilibrium: the amplitude of the e.p.c.I will thus depend on the affinity constant of the reversible reaction between ACh and R. It is concluded that by decreasing the pH, the affinity constant is decreased.

The use of equivalent electronic circuits in simulating physiological processes

This paper is a report on one of the modern approaches to teaching physiology to postgraduate medical students. The aim is to promote qualitative as well as quantitative analog thinking about physiological processes. To meet this aim the concept of equivalent electronic circuits was introduced in teaching. Two examples of simulation of physiological phenomena by equivalent electronic circuits are described: (1) a pump for building-up the concentration gradient of a solute and (2) drug distribution in body compartments after single or repeated administration and extracellular volume measurement. The use of the latter circuit in teaching was tested in two generations of postgraduate medical students. They showed an increasing interest for this type of teaching because simulation graphs were almost identical to those shown in textbooks and physicians manuals.

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.

Simulation of the Frank-Starling Law of the Heart.

We developed a lumped parameter, computer-based model of an equivalent electronic circuit for a one-atrium one-ventricle (frog) heart attached to a vascular circuit, to simulate a basic concept of cardiovascular physiology, the Frank-Starling Law of the Heart. A series of simulations was performed, to observe changes in cardiovascular variables (e.g., arterial pressure, ventricular volume, and valve flows) if either preload or afterload was increased. The simulated data agreed qualitatively, and quantitatively when experimental data are available, with data obtained on amphibian or on mammalian myocardium. In addition, the data obtained in these simulations improve our understanding of the mechanism(s) whereby the heart muscle adapts itself to increased distension (increased preload) or to impeded systolic contraction (increased afterload). The analysis of the measured valve flows suggests that the ventricle is a highly input sensitive pump because the input pressure determines the diastolic distension and, consequently, the force of ventricular systolic contraction. On the other hand, the ventricle is a relatively output insensitive pump. Therefore, not only atrium contraction, but also predominantly the preceding ventricular systolic contraction is the main mechanism of the subsequent diastolic ventricular filling. We conclude that the presented model enables the study of basic concepts of cardiovascular physiology.

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

SummaryThe use of cholinesterase (CHE) inhibitors provided valuable information about the mechanism(s) of neuromuscular transmission, but questions on side effects at the level of AChactivated 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 μm) 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 <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 μm 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.

Simulation of Exercise-Induced Syncope in a Heart Model with Severe Aortic Valve Stenosis

Severe aortic valve stenosis (AVS) can cause an exercise-induced reflex syncope (RS). The precise mechanism of this syncope is not known. The changes in hemodynamics are variable, including arrhythmias and myocardial ischemia, and one of the few consistent changes is a sudden fall in systemic and pulmonary arterial pressures (suggesting a reduced vascular resistance) followed by a decline in heart rate. The contribution of the cardioinhibitory and vasodepressor components of the RS to hemodynamics was evaluated by a computer model. This lumped-parameter computer simulation was based on equivalent electronic circuits (EECs) that reflect the hemodynamic conditions of a heart with severe AVS and a concomitantly decreased contractility as a long-term detrimental consequence of compensatory left ventricular hypertrophy. In addition, the EECs model simulated the resetting of the sympathetic nervous tone in the heart and systemic circuit during exercise and exercise-induced syncope, the fluctuating intra-thoracic pressure during respiration, and the passive relaxation of ventricle during diastole. The results of this simulation were consistent with the published case reports of exertional syncope in patients with AVS. The value of the EEC model is its ability to quantify the effect of a selective and gradable change in heart rate, ventricular contractility, or systemic vascular resistance on the hemodynamics during an exertional syncope in patients with severe AVS.