Further evidence for two modes of hypothermia damage.

The Arrhenius plot of inactivation (killing) rates of V-79 Chinese hamster cells exposed to hypothermia contains a break at about 8 degrees C, which corresponds to the minimum inactivation rate, implying that there are distinct hypothermic damage mechanisms above (Range I = 8 to +25 degrees C) and below (Range II = 0 to +8 degrees C) 8 degrees C. Several membrane-permeable hydroxyl free radical scavengers, N-acetylhomocysteinethiolactone (citiolone), dimethylthiourea (DMTU), and dimethyl sulfoxide (DMSO), were tested for their ability to protect cells exposed to hypothermic temperatures of 10 degrees C (Range I) or 5 degrees C (Range II) as a function of time in a system that is uncomplicated by previous hypoxia. Citiolone (3 mM) protected cells in Range I, but not in Range II. To date, citiolone is the only agent that protects in Range I. Adenosine was of no benefit in Range I. Glycine (5 mM) protected cells in Range II, but not in Range I. DMSO (10 mM) was ineffective in Range II, while DMTU (10 mM) protected cells in Range II, but not in Range I. The combination of DMTU and citiolone had a synergistic protective effect on the cells during 10 degrees C exposure (Range I). However, the combination of DMTU and citiolone is neither synergistic nor additive at 5 degrees C (Range II).