Specific aims: A few species of frogs are the only vertebrates known to tolerate freezing. This study examines the physiological basis of freeze tolerance in the wood frog, Rana sylvatica. Research will focus on two primary objectives: 1. To characterize systemic and metabolic responses from the onset of ice nucleation in body fluids until ice formation is complete. The specificity of tissue accumulation of glucose and lactate, the distribution of ice and water, and cardiac function will be monitored. Also, the significance of variable freezing and thawing rates will be evaluated. 2. To examine the physiological triggering mechanisms responsible for the rapid mobilization of glucose from the liver. Regulation of glycogenolysis in the liver will be examined in terms of intrinsic and extrinsic (neuroendocrine) controls. Health relatedness and long-term objectives: An ever growing demand exists in the biomedical community for viable, long-term storage of organs to be used for transplantation; however, attempts at the cryopreservation of mammalian organs have met with limited success. From a long-term perspective freeze-tolerant frogs may provide an important vertebrate model system for the study of tissue and organ cryopreservation. Furthermore, a 70-fold increase in blood glucose levels occurs concomitantly with tissue freezing. The accumulated glucose functions as a cryoprotective agent. In other vertebrates this hyperglycemic response would be interpreted as potentially lethal or a severely diabetic state. Therefore, the wood frog may be useful in the study of intermediary metabolism including the regulation of glucose metabolism and hypoxia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15HL040535-01
Application #
3440062
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1988-05-01
Project End
1990-04-30
Budget Start
1988-05-01
Budget End
1990-04-30
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Miami University Oxford
Department
Type
Schools of Arts and Sciences
DUNS #
041065129
City
Oxford
State
OH
Country
United States
Zip Code
45056
Costanzo, J P; Lee Jr, R E; Wright, M F (1992) Cooling rate influences cryoprotectant distribution and organ dehydration in freezing wood frogs. J Exp Zool 261:373-8
Costanzo, J P; Lee Jr, R E (1991) Freeze-thaw injury in erythrocytes of the freeze-tolerant wood frog, Rana sylvatica. Am J Physiol 261:R1346-50
Costanzo, J P; Lee Jr, R E; Wright, M F (1991) Effect of cooling rate on the survival of frozen wood frogs, Rana sylvatica. J Comp Physiol B 161:225-9
Costanzo, J P; Lee Jr, R E; Wright, M F (1991) Glucose loading prevents freezing injury in rapidly cooled wood frogs. Am J Physiol 261:R1549-53
Layne Jr, J R; Lee Jr, R E (1989) Seasonal variation in freeze tolerance and ice content of the tree frog Hyla versicolor. J Exp Zool 249:133-7
Layne Jr, J R; Lee Jr, R E; Heil, T L (1989) Freezing-induced changes in the heart rate of wood frogs (Rana sylvatica). Am J Physiol 257:R1046-9