Article

Therapeutic window of selective profound cerebral hypothermia for resuscitation of severe cerebral ischemia in primates.

Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Journal of neurotrauma (Impact Factor: 4.25). 06/2009; 26(11):2107-12. DOI: 10.1089/neu.2009-0889
Source: PubMed

ABSTRACT It is well recognized that brain death starts to occur just 4-6 min after cardiac arrest, and few attempts at resuscitation succeed after 10 min of severe cerebral ischemia and anoxia. We sought to determine the therapeutic window of selective cerebral profound hypothermia of primates following severe cerebral ischemia in primates. Fourteen rhesus monkeys with severe cerebral ischemia were divided into four groups: normothermia (n = 3); profound hypothermia I (n = 4), with cooling initiated 10 min after ischemia; profound hypothermia II (n = 4), with cooling initiated 15 min after ischemia; and profound hypothermia III (n = 3), with cooling initiated 20 min after ischemia. Severe cerebral ischemia was induced by clamping both the internal and external carotid arteries, as well as the internal and external jugular veins. Profound cerebral hypothermia (15.8 degrees +/- 0.9 degrees C) was achieved and maintained for 60 min, and the animals were then re-warmed gradually. All four animals in hypothermia group I survived without any neurological deficits. Only 1 animal survived and 3 animals died in hypothermia group II. All 4 animals died in both hypothermia group III and the normothermia group. Neurological functions were normal in all surviving animals, and MRI scans showed no cerebral infarction in these animals. Microscopic examination showed no injured neurons in the hippocampus and cerebral cortex of the surviving animals, and showed that the heart, lung, liver, and kidneys were normal in these animals. Our data indicate that post-ischemic profound cerebral hypothermia provided significant cerebral protection with no systemic complications, and that the effective therapeutic window is more than 10 min, but less than 15 min, after severe cerebral ischemia.

0 Bookmarks
 · 
67 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Selective cerebral deep hypothermia and blood flow occlusion can enhance brain tolerance to ischemia and hypoxia and reduce cardiopulmonary complications in monkeys. Excitotoxicity induced by the release of a large amount of excitatory amino acids after cerebral ischemia is the major mechanism underlying ischemic brain injury and nerve cell death. In the present study, we used selective cerebral deep hypothermia and blood flow occlusion to block the bilateral common carotid arteries and/or bilateral vertebral arteries in rhesus monkey, followed by reperfusion using Ringer's solution at 4°C. Microdialysis and transmission electron microscope results showed that selective cerebral deep hypothermia and blood flow occlusion inhibited the release of glutamic acid into the extracellular fluid in the brain frontal lobe and relieved pathological injury in terms of the ultrastructure of brain tissues after severe cerebral ischemia. These findings indicate that cerebral deep hypothermia and blood flow occlusion can inhibit cytotoxic effects and attenuate ischemic/hypoxic brain injury through decreasing the release of excitatory amino acids, such as glutamic acid.
    Neural Regeneration Research 01/2013; 8(2):143-8. · 0.14 Impact Factor