City Research Online

Abstract

A pulsatile mathematical model of the human cardiovascular system suitable for the study of short-term haemodynamics was developed. The circulatory fluid mechanics section of this model was based on lumped parameter approximations with linear arterial segments, nonlinear venous segments and time-varying compliance pumping in the four heart chambers, Neural control was added in the form of a mathematical description of the aortic arch and carotid sinus baroreceptors and central nervous regulation of heart rate, peripheral resistance, myocardial contractility and venous tone. The model was intended for the study of haemodynamics following the injection of a cardiovascular agent so a mathematical description of the injection, transport, action and breakdown of a single drug was included making the overall model of order 61.

The model was implemented as a digital computer simulation and reasons for the choice of simulation technique, programming language and numerical method were presented. Attention was given to techniques for computing a steady state solution and also the treatment of constrained state variables, differentiation and algebraic loops.

The digital simulation was validated by comparison with data from humans and comparable animals. Essential features of significant variables were checked and the model was subjected to tests such as orthostasis, blood volume changes, the Valsalva manoeuvre and cardiac pacing. In these respects the model performed realistically. In the pacing tests, the cardiac output changed very little and so a remarkably close linear relationship between stroke volume and heart period was found, The beat—by-beat estimation of total peripheral resistance from mean arterial pressure and cardiac output was found to be unreliable during rapid transients.

When injections of methoxamine, isoprenaline and noradrenaline were simulated, realistic responses were obtained. In the case of noradrenaline, venoconstriction had to be included to obtain the bradycardia observed in practice. It was concluded that the model had an explanatory usefulness and potential as a cardiovascular agent design aid in pharmacology.

Publication Type:	Thesis (Doctoral)
Subjects:	Q Science > QP Physiology R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica
Departments:	School of Science & Technology > School of Science & Technology Doctoral Theses Doctoral Theses

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