The determination of the minimum alveolar concentration (MAC) of any inhalation
anaesthetic requires repeated application of the stimulus. The investigation of the
influence of body temperature on MAC in the same animal, requires even more
applications of the stimulus. The use of what is commonly known as a "supramaximal
stimulus", beyond which there is no increase in MAC with any further increase in
stimulus intensity, is generally held to provide for the reproducibility of MAC.
However, there are many conflicting reports with regard to the MAC values obtained
using "supramaximal stimuli" and with the interpretation of results.
In this study the unreliability of the "supramaximal stimulus", in the form of tail
clamping using a haemostat for the determination of MAC of halothane in the rabbit,
was established. The use of this technique was demonstrated, both grossly and
histologically, to cause severe trauma and lacerations that may have altered the
sensitivity of the sensory mechanisms as indicated by the great variability in the values
of MAC obtained on subsequent determinations in the same animal. Also, the
technique appeared to disregard modern physiological concepts on receptor
thresholds, inflammation and hyperalgesia.
Therefore, it was decided to explore more reliable techniques of stimulation.
Controlled mechanical and heat stimulators were devised and used for the
determination of MAC of halothane in the rabbit as the body temperature was
manipulated to test the effect of environmental heating or cooling on MAC.
The mechanical stimulator is a form of pincer driven by compressed air, and is
operated from a control panel with a manual trigger. It is capable of delivering a
precise stimulus at a preselected pressure to the target site (ear pinna). The stimulus
was calculated in terms of Newtons per unit surface area after calibration of the
device using gram weights. The heat stimulator was designed to deliver a controlled,
preset focal heat stimulus from a heat lamp for a preselected duration The device is
operated through a system of electronic circuits controlling the temperature and time.
With both stimulators, a just noxious level of stimulation was applied.
The mechanical and heat stimulators shared some common advantages over the
established clamping techniques used for the determination of MAC. Firstly, both of
them were shown to be capable of delivering precise stimuli in terms of amount,
duration and rate of application. The control of such components of the stimulus is
essential for the reproducibility and interpretation of results, particularly in the ever
growing field of comparative studies. Secondly, the stimulus applied by both
stimulators was recordable. This allows for the calculation and the calibration of the
applied stimulus and, together with the electronically measured and recorded
movement response, it was also possible to calculate the response time.
At normothermia, the MAC values of halothane determined in the rabbit usingnondestructive stimuli from either stimulator were found to be consistent and
reproducible. Hyperthermia (rectal temperature of 40.6 °C +/- 0.3 (SD) was
demonstrated to cause a significant increase in MAC of halothane (12.3% per 1°C
rise in body temperature) when determined using a mechanical stimulus of 1.37 +/-
0.04 (SD) N/mm^. On the other hand, no significant difference was detected in MAC
determined using a focal heat stimulus of 54.35 °C +/- 0.09 (SD) in hyperthermic
rabbits (41.6 °C +/- 0.4 (SD). Hypothermia of 4 °C was shown to reduce the MAC
of halothane in the rabbit by 50% (12.8% per 1 °C drop in body temperature) to a
focal heat stimulus of 54.3 °C, and by 35.1% (9 % per 1 °C decrease in body
temperature) to a mechanical stimulus of 1.39 - 1.41 N/mm^. By extrapolation of
results, it was predicted that the "anaesthetising body temperature", at which no
halothane would be required to abolish movement response to such stimuli, would be
31.0 °C and 27.7 °C for the heat and mechanical stimuli respectively. It is concluded
that, normal doses of potent anaesthetics similar to halothane should probably be
considerably reduced in hypothermic rabbits, which must be closely monitored for
signs of overdose.
In the initial stages of this study some problems were encountered regarding the
determination of MAC in hyperthermic rabbits due to the difficulty in the control of
animal heating. As a result a section of this thesis was devoted to the establishment of
a controlled and reliable heating and cooling protocol, with some emphasis on
selected cardiopulmonary parameters and some stimulus-related responses. A body
temperature of 42.0 °C appeared to represent a critical temperature in the rabbit
above which the normal physiological responses are interfered with and also above
that temperature, induced cooling was ineffective in reducing the body temperature.
Stimulus-related responses, other than movement, included changes in arterial blood
pressure, apnoea and hyperpnoea. Such responses, particularly those of the arterial
blood pressure, showed both quantitative and qualitative inconsistency. Therefore it
was concluded that these responses are not reliable end points for the determination
of MAC in the rabbit. On the other hand, the provoked movement of the head and or
limbs, remains unchallenged as the most reliable end point for the determination of