Biomedical subjects
Publications and source records attributed to G M Fahy.
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Slowly frozen cells are said to be subject to solution effects injury. An understanding of the mechanism of solution effects injury depends upon an understanding of the compositional changes brought about in the extracellular solution during the freezing process. To facilitate analysis of the mechanisms of freezing injury during slow cooling, empirical equations have been developed which permit a description of these changes in composition for the NaCl-dimethylsulfoxide-water ternary system and for the NaCl-glycerol-water ternary system. The equations describe the region of the phase diagram in which compositional changes are brought about only as a result of the precipitation of ice. The present phase diagram equations may be rearranged to give expression for composition variables such as water content, salt concentration, unfrozen fraction of the solution, etc., which may be employed in the analysis of the relationship between solution composition and solution effects injury.
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The failure of complex mammalian organs, such as the kidney, to function following freezing to low temperatures is thought to be due largely to mechanical disruption of the intercellular architecture by the formation of extracellular ice. Classical approaches to the avoidance of ice formation through the imposition of ultra-rapid cooling and warming rates or by gradual depression of the equilibrium freezing point during cooling to -80 degrees C have not been adequate. An alternative approach relies on the ability of highly concentrated aqueous solutions of cryoprotective agents to supercool to very low temperatures. At sufficiently low temperatures, these solutions become so viscous that they solidify without the formation of ice, a process termed vitrification. When embryo suspensions are cryopreserved using conventional procedures, this supercooling behaviour allows intracellular vitrification, even in the presence of extracellular ice. We have therefore used mouse embryos to examine the feasibility of obtaining high survival following vitrification of both the intra- and extracellular solutions and report here that in properly controlled conditions embryos seem to survive in high proportions after cryopreservation in the absence of ice.
This study describes the use of a blood perfusion apparatus to assess the renal function of isolated kidneys. Eight fresh kidneys were obtained from healthy rabbits and perfused with blood at 36 degrees C for 2 hours. Rabbit blood was drawn and diluted to a hematocrit of 25%. The kidneys were evaluated for their capacity to support life in an autograft model. Blood and urine samples were taken at regular time intervals during kidney perfusion. Serum creatinine was measured in surviving rabbits after transplantation. Over the course of the perfusion, arterial pressure was maintained at 87.2 +/- 5.5 mm Hg. The renal blood flow (3.7 +/- 1.0 ml/min per g) and urine output (0.11 +/- 0.04 ml/min per g) were continuously monitored. Glomerular filtration rate (0.29 +/- 0.02 ml/min per g) and fractional reabsorption (FR) of sodium and glucose indicated appreciable tubular function (FR(Na) = 67.9 +/- 8.5%, FR(Glu) = 91.2 +/- 5.8%). Protein was excluded from urine at 99.8% +/- 0.1%. After transplantation, the peak creatinine was 6.8 +/- 3.2 mg/dl at 1.90 +/- 0.92 days for the seven surviving rabbits and was above 16 mg/dl for the only rabbit that died 4 days after operation. The level of free hemoglobin generated at the end of the perfusion (2.6% +/- 2.8%) was correlated with the postoperative peak creatinine (r2 = 0.84). Perfusion of seven additional kidneys by using the roller pump lead to a final hemolysis of only 0.34 +/- 0.14%. Kidneys transplanted after 2 hours of blood perfusion were able to resume normal function and support life. Hemolysis was a measurable stress factor causing delayed function of the kidney after transplantation. Introduction of a roller pump significantly reduced the hemolysis.
A new system for perfusing organs with cryoprotective agents or other solutions is described. It represents the first system that combines the sophistication and versatility required for successful organ cryopreservation protocols with the experimental ease and reproducibility required for sustaining a long-term research or organ-processing effort with a high throughput of successfully perfused organs. Operation is simple, fully documented, and readily checked by visual means, and maintenance is not difficult. It appears that this system could be adapted for use with a wide variety of organ perfusion protocols and could lead to improved results and greater patient safety with less human effort.