In Reply:—

We read carefully the comments of Drs. Albin and White on our recent article. 1As indicated by these authors, induction of spinal cord hypothermia (10°C) after traumatic spinal injury is still effective in providing protection if initiated 4 h after injury. 2,3In contrast, in our study, we observed a significant protection only if spinal hypothermia (27°C) was initiated immediately (5 min) after ischemia. Although the differences between the therapeutic efficacy of spinal hypothermia after spinal trauma and spinal ischemia are not clear, there are several points that need to be addressed.

After injurious intervals of spinal ischemia, the development of irreversible neuronal degeneration shows very rapid onset. Using Nauta silver impregnation technique in rat, rabbit, or dog spinal ischemia models, we have found that irreversible neuronal degeneration is clearly developed as soon as 60–120 min after reflow following injurious intervals of ischemia. 4–7These data indicate that the process of irreversible neuronal degeneration is likely initiated during the early period (0–30 min) of reflow. Importantly, based on the data from our study, this process shows high temperature sensitivity. The lack of hypothermic protection after a longer period of normothermic reflow thus likely reflects the fact that the process of irreversible degeneration was already initiated or completed.

In our study, intrathecal temperature was measured during and after a period of subcutaneous cooling. It is possible that the magnitude of the decrease in spinal parenchymal temperature does not completely reflect measured intrathecal temperature. However, in our previous methodologic study 8describing this cooling technique, we showed that there is a 2–3°C temperature gradient if measured on dorsal versus  ventral spinal cord surface. Based on these data, we believe that spinal temperature is in the range of temperatures measured between dorsal and ventral spinal cord surface. Accordingly, measurement of spinal somatosensory evoked potentials showed a temperature-dependent increase in the N3 (postsynaptic) component during the period of cooling and a return to baseline after rewarming.

Based on our previous data describing a very rapid onset of irreversible neuronal degeneration after spinal ischemia, the possibility that the therapeutic window could be enlarged if intrinsic spinal cord temperature were reduced to lower levels is uncertain. However, it is possible that the fraction of neurons undergo prolonged or delayed degeneration and that rescue of these neurons will eventually improve outcome. In this case, it is possible that deeper hypothermia (10–20°C) will be more effective in protecting this neuronal pool than temperatures (27°C) tested in our study. Accordingly, it would be important, using localized epidural or intrathecal cooling techniques 2,3,6,9(which are required to achieve deep spinal hypothermia), to determine the efficacy of such hypothermic treatment.

Kakinohana M, Taira Y, Marsala M: The effect of graded postischemic spinal cord hypothermia on neurological outcome and histopathology after transient spinal ischemia in rat. A NESTHESIOLOGY 1999; 90:789–98
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Dinda M, Galik J, Marsala J, Vanicky I, Marsala M: Sciatic nerve stimulation increases the degree of histopathological damage in lumbosacral segments after short lasting spinal ischemia in rabbit. Restorative Neurol Neurosci 1995; 3:145–50
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Marsala M, Vanicky I, Galik J, Radonak J, Kundrat I, Marsala J: Panmyelic epidural cooling protects against ischemic spinal cord damage. J Surg Res 1993; 55:21–31
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Marsala M, Galik J, Ishikawa T, Yaksh TL: Technique of selective spinal cord cooling in rat: Methodology and application. J Neurosci Methods 1997; 74:97–106
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