Experimental Evidence of Cerebral Injury from Profound Hypothermia During Cardiopulmonary Bypass

Abstract

Choreoathetosis, seizures, and impaired mental development continue to occur in children undergoing cardiopulmonary bypass (CPB) and profound hypothermia with or without circulatory arrest. Although there is some evidence that the hypothermia itself may be causing these neurologic problems, skepticism remains because of lack of evidence from experimental studies simulating the clinical setting. In this experimental study, we examined the effect of profound and moderate hypothermia on the brain while maintaining normal flow rates during CPB. Ten adult mongrel dogs equally divided into two groups were anesthetized and subjected to CPB and varying levels of hypothermia (group 1, < or = 15 degreesC; group 2, < or = 2 degreesC). Both groups were kept at the desired temperature for 1 hour prior to rewarming and discontinuation of CPB. The dogs were euthanized 4-6 weeks later and neuropathologic studies were performed. The mean CPB flow rates during cooling and at the desired rectal temperature were comparable in both groups: group 1, 108 +/- 10 ml/kg/min versus 106 +/- 7 ml/kg/min in group 2 (p = NS) and 95 +/- 12 ml/kg/min in group 1 versus 101 +/- 5 ml/kg/min in group 2 (p = NS). Because of the difference in temperature between the two groups, the mean cooling time (onset of CPB to desired rectal temperature) was longer in group 1 (70 +/- 14 minutes) than in group 2 (28 +/- 11 minutes, p = 0.007). Hence, the total mean CPB time was also longer in group 1 (198 +/- 25 minutes) than in group 2 (143 +/- 13 minutes, p = 0.002). The lowest mean blood and rectal temperature achieved in group 1 were 11 +/- .9 degreesC and 12 +/- 1 degreesC versus 29 +/- .4 degreesC (p < 0.001) and 30 +/- .6 degreesC (p = 0.001), respectively, in group 2 (p = 0.001). Neuronal loss and degeneration was noted in all dogs in group 1 ranging from 2 to 8 cells per 1000 cells counted compared to none in group 2 (p = 0.05). These lesions occurred in both the basal ganglia and the cortex, although they were more marked in the caudate when compared to the cortex and cerebellum. Both in the cortex and in the caudate, neuronal loss was more marked around the capillaries. We conclude that the use of profound hypothermia of < or =15 degreesC and maintenance of normal flow rates during cooling at this temperature for 1 hour produces neuronal loss and degeneration in the brain. These lesions being more marked around capillaries points to the vulnerability of the neurons, probably because of their high lipid content to injury from the cold perfusate.

Long term behavioural outcome after neonatal arterial switch operation for transposition of the great arteries

“…This may be owing to a direct effect, as deficits in perioperative cerebral perfusion predominantly exert negative influences on vulnerable brain regions such as the frontal brain lobes, hippocampus, and cerebellum. [31][32][33] Impaired neurological status and reduced endurance capacity predicted increased stress from illness as assessed by the children themselves. As in other studies, patients with cerebral palsy, ataxia, and/or global developmental delay reported particularly poor self esteem and health related quality of life, 34 35 and problems such as anxiety and depression.…”

l-Dopa effect on frequency-dependent depression of the H-reflex in adult rats with complete spinal cord transection

“…We followed the Scheidtmann, et al (2001) protocol (28) for humans by giving rats DOPA 30 minutes prior to exercise therapy in order to take advantage of the peak time of the DOPA effect. Studies of the effects of monoaminergic agents in rats following unilateral motor cortex ablation indicate that the motor recovery occurs only if physical training is performed during the peak of drug availability [30]. …”

Anesthetic Protection of Neurons Injured by Hypothermia and Rewarming

“…10 found that PH, independent of cerebral ischemia or other factors, causes central nervous system injury in swine. Damage and loss of hippocampal neurons are prominent findings following PH with or without circulatory arrest 6,9 , similar to hippocampal damage caused by global ischemia 11 .…”

“…However, a number of laboratory studies suggest that PH/rewarming (RW) injures neurons separately from injury caused by cerebral blood flow insufficiency. For example, in dogs cooled to 12 °C during normal blood flow cardiopulmonary bypass, DeLeon et al documented extensive neurologic damage in the cerebrocortex 9 . Similarly, Watanabe et al 6 found widespread and persistent neural injury, including substantial loss of hippocampal neurons, in dogs following normal flow cardiopulmonary bypass in which the dogs were merely cooled to 20 °C and not subjected to any ischemic stress.…”