京都大学 / 新制・課程博士 / 博士(医学) / 甲第25006号 / 医博第5040号 / 新制||医||1070(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 高橋 淳, 教授 荒川 芳輝, 教授 林 康紀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Carolina Rinse (CRS) has been shown to be effective in decreasing vascular permeability and neutrophil infiltration in reperfused equine small intestine. The objective of this study was to show that CRS applied topically and intraluminally could prevent immediate reperfusion injury after low flow ischemia or distention in the equine jejunum. Materials & Methods: Two groups of 5 horses were used to evaluate CRS treatment after low-flow ischemia (Group 1) and intraluminal distention (Group 2) of distal jejunum. Mesenteric blood flow, osmotic reflection coefficient (ORC), wet weight to dry weight ratios (WW/DW), and neutrophil accumulation in the serosa were measured. ORC is defined as the lymph protein concentration to plasma protein concentration ratio subtracted from one (1- Cl / Cp) at maximal lymph flow. The ORC from baseline values and at 60 minutes after initiating reperfusion was compared between Groups 1 and 2. Pair wise comparisons were made for mesenteric blood flow, tissue volume, neutrophil number, and WW/DW proximal control and CRS treated jejunal segments were made using a Mann Whitney U test (P< 0.05). Results: The mean ORC of bowel treated topically and intraluminally with CRS was similar to that recorded in normal bowel or ischemic intestine treated with CRS by arterial perfusion. The ORC after distention and decompression increased and was similar to that reported in untreated intestine. The WW/DW after both ischemia and distention increased compared to the proximal control segments. There was no difference in neutrophil number in either ischemic or distended intestine compared to the proximal control segments. Discussion: Carolina CRS was effective in preventing alterations in microvascular permeability during reperfusion afterischemia but not distention. Neutrophil migration curtailed in both groups suggesting that combined topical and intraluminal application of CRS to ischemic intestine may reduce the acute inflammatory responses during reperfusion thereby decreasing complications after ischemia or distention. / Master of Science

The development of an organ preservation system (primarily kidneys and livers, but could be adapted to fit hearts, lungs, and even limbs in the future) that can provide surgeons and doctors with real-time quantitative feedback on the health of the organ would be a significant improvement on current transplant practices. This organ transport system will provide surgeons and doctors the opportunity to make more educated decisions towards whether or not to proceed with organ transplantation. Here, we discuss the use Smart Perfusion's organ preservation system as a platform for determining the optimal perfusion temperature of an organ. Porcine kidneys were procured and perfused with a modified PBS solution on the Vasowave™. While on this organ preservation system, a heart emulating pressure waveform (90/50 mmHg) was generated and sent to the specimen. The pressure response, flow rate, temperature, pH, dissolved oxygen content, and conductivity of the fluid stream were all monitored throughout the duration of experimentation. In addition to inline sensors, IR imaging captured the surface temperature of the organ while on the system. Lastly, the use of a combined heat flux-temperature (CHFT) sensor, previously developed at Virginia Tech, was applied for the first time to monitor and measure local tissue perfusion of an explanted organ. A total of 12 experiments were performed (6 at a set fluid temperature of 15°C, and 6 at 20°C). All system data was collected, statistically evaluated and finally compared against blind histological readings (taken at the termination of each experiment at the hilum and pole) to investigate the effects of temperature on organ vasculature. The results of this experiment indicated that the effects of temperature on explanted kidneys can be affectively measured using a non-invasive bioheat perfusion sensor. Specifically, the lower temperature group of kidneys was measured to have lower perfusion. Furthermore, an enhancement to the CHFT sensor technology (CHFT+) was developed and tested for compliance. A controllable thin filmed heat resistor was added to the CHFT assembly to replace the current convective thermal event. This enhancement improved the measured heat flux and temperature signals and enables autonomy. Also, the thin and semi-flexible nature of the new CHFT+ sensor allows for perfusion measurements to be taken from the underside of the organ, permitting a quantitative measure of pressure ischemia. Results from a live tissue test illustrated, for the first time, the effects of pressure ischemia on an explanted porcine kidney. / Master of Science

published_or_final_version / Medicine / Master / Master of Philosophy