| Abstract: | In order to study any early sign of rejection of pancreas transplantation, rhythmometry was carried out on female adult inbred Lewis rats. Animals previously kept in continuous light, more or less synchronized in frequency by cyclic human activities, were transferred to a regimen of light (L) and darkness (D) alternating at 12-h intervals in single cages at the room temperature of 24 +/- 1 degrees C, with food and water ad libitum. At this time under ether anesthesia, temperature transensors were implanted in healthy rats and rats rendered diabetic by the administration of streptozotocin. Some of the diabetic rats were left untreated; casual blood sampling showed gross hyperglycemia. Other rats were treated by pancreatic grafts from ethionine-prepared donors, either by isografts (in rats of the Lewis strain) or by allografts (of the pancreas from inbred Fischer rats transplanted to Lewis rats). Intraperitoneal temperature was telemetered at 10-min intervals for 3 weeks following transplantation. Urine volumes were determined from rats housed in metabolic cages. Data were analyzed rhythmometrically. Chronobiological serial sections and single cosinors served this purpose. Following sensor implantation and transfer to an LD 12:12 regimen, the adjustment of the thermal acrophase consistently near the middle of the daily dark span occurred within approximately 7 days in healthy rats and in streptozotocin-diabetic rats cured by isograft. Thermal acrophase adjustment was slower for animals rendered diabetic by streptozotocin and left untreated or for animals thus rendered diabetic which had rejected the pancreatic allograft (as documented by hyperglycemia in casually sampled blood). The eventual synchronization of the circadian temperature rhythm of allografted rats differed from one rat to the other and, for some allografted animals, from the consistent synchronization of the circadian rhythm in telemetered intraperitoneal temperature of diabetic and non-diabetic Lewis rats. The acrophase of the circadian rhythm in urine volume of healthy rats or of a rat with a pancreatic isograft (which cured a prior streptozotocin-induced diabetes) differed with statistical significance from those of rats with untreated diabetes, some in this state after the rejection of a pancreatic allograft. Both urine volume and core temperature are ready marker rhythms, not only for rats but also for human beings. Both variables can be self-monitored by the cooperation of instructed but not necessarily extensively educated patients. Temperature, in particular, can also be monitored with automatic devices and alterations of certain of its rhythm characteristics may signal changes preceding fever. The use of such admittedly unspecific yet eminently practical and possibly informative marker rhythmometry awaits clinical testing. |
