Direct and Indirect Measurement of the Effects of Halothane and Isoflurane on Arterial Wall Mechanics
Date of Award
Dissertation - Restricted
Doctor of Philosophy (PhD)
The basic mechanism of action for most anesthetic agents is not completely understood. In addition to anesthesia, these agents produce a variety of side effects on the performance of the cardiovascular system. The side effects may be compounded by underlying disease or pharmacologic states. It is therefore important to gain as complete an understanding as possible of all the effects of an anesthetic agent on cardiovascular function under a wide variety of conditions. Before such determinations can be made, an adequate methodology for quantifying cardiovascular function must be developed. Such methodology has previously been developed and applied to study the effects of anesthetic agents on left ventricular systolic and diastolic function. However, the methodology for quantifying the effect of these agents on arterial system function has been less well studied. In this dissertation, a quantitative methodology for directly determining the effects of halothane and isoflurane on arterial mechanical properties is developed and implemented. The measures of arterial mechanical properties obtained by direct measurements are compared with indirect measurements of Windkessel model parameters estimated from aortic input impedance spectra. A brief physiological review of cardiovascular function is presented in Chapter 1. The mechanical and hemodynamic events of the cardiac cycle are reviewed. The mechanical properties of the arterial wall as well as physiologic wall structure and mechanics, are described. Chapter 2 introduces the concept of ventriculo-arterial coupling. The concepts of aortic input impedance and the three element Windkessel model of afterload are explained in relation to coupling frameworks. The ability of coupling frameworks to quantify ventricular efficiency and optimization of ventriculo-arterial coupling relationships are also described. In Chapter 3, a study of the effects of halothane and isoflurane on aortic input impedance in chronically instrumented dogs is presented. Aortic input impedance, determined by spectral analysis of aortic pressure and flow waveforms, is quantified by estimating corresponding three element Windkessel parameters. Chapter 4 details an in vitro model and corresponding 3-dimensional finite element model of an isolated aorta segment. The models were designed to examine the feasibility of measuring aortic segmental volume by the conductance catheter technique. Such a direct measurement of aortic segmental dimensions could lead to more accurate estimations of arterial mechanical properties described in Chapter 3. Measurement made by the conductance catheter technique are compared to those made simultaneously by sonomicrometry. The finite element model enables the corresponding electric field to be determined. A study of the effects of halothane and isoflurane on direct measurements of canine aortic pressure-volume and pressure diameter relations in vivo is presented in Chapter 5. The techniques for measuring aortic segmental volume (and diameter) developed in Chapter 4 are applied in vivo. Direct measurements of arterial wall mechanical properties by sonomicrometry and conductance are compared to those measured indirectly and simultaneously via aortic input impedance spectra. Chapter 6 provides an overview and discussion of the results of the investigations of chapters 3, 4 and 5. Potential areas of future investigation are also detailed.