Computer Controlled Isolated Organ Perfusion PDF Download

The thesis describes the design and construction of a perfusion apparatus suitable for cooling and rewarming the isolated rat heart, and its interfacing to a process control computer, to enable studies into sub-zero preservation of the rat heart to be carried out. Pilot experiments using this apparatus are presented. This is the first application of computer controlled experimental apparatus to investigation of the organ storage problem. Current techniques in whole organ storage are reviewed, and the benefits of the application of control technology to the organ preservation problem are summarised. The development of a surgical technique for the removal and cannulation of the rat heart is described, and initial experience in normothermic rat heart perfusion using a standard Langendorff perfusion apparatus is discussed. An improved perfusion apparatus, suitable for application to sub-zero cooling experiments was developed, instrumented and interfaced to a process control computer. The perfusate pH, partial pressure of oxygen and carbon dioxide were measured on-line, together with the perfusion pressure, mechanical activity and ECG of the heart. The temperature of the heart at the aorta was measured by means of a copper/constantan thermocouple. The computer program allowed accurate, interactive calibration of the instrumentation, accurate control of temperature at the aorta, with rates of change of up to + or- 5 degrees C per minute being obtainable, in the temperature range + 40 degrees C to - 20 degrees C, and controlled addition of cryoprotective agent (Ethylene Glycol) to the perfusate, to a maximum concentration of 6M. Measured variables were logged on a remote teletype at regular intervals, and a keyboard input facility enabled modification of experimental parameters during experimental runs, and initiation of temperature and CPA addition profiles from the remote teletype keyboard. An experimental plan for the investigation of heart preservation is proposed. Computer-controlled experiments in normothermic perfusion,.cooling and rewarming at various rates and cooling to sub-zero temperatures in the presence of 3M ethylene glycol are described. In all cases strong, regular mechanical activity was retained at the end of the experiment. A method of evaluating damage incurred during these experiments is indicated, using perfusion pressure as the index of damage. The results of initial experiments into the mechanism of mass transfer of ethylene glycol across red blood cell membranes are discussed. Recommendations are made for the improvement of the apparatus in the light of the experiments already performed, and for the implementation of improved computer facilities for experimental data processing. Further work in both the engineering and biological fields is proposed to enable the solution of the organ preservation problem.