Head cooling with mild systemic hypothermia in anesthetized piglets is neuroprotective

Abstract

Hypothermia is potentially therapeutic in the management of neonatal hypoxic-ischemic brain injury. However, not all studies have shown a neuroprotective effect. It is suggested that the stress of unsedated hypothermia may interfere with neuroprotection. We propose that selective head cooling (SHC) combined with mild total-body hypothermia during anesthesia enhances local neuroprotection while minimizing the occurrence of systemic side effects and stress associated with unsedated whole-body cooling. Our objective was to determine whether SHC combined with mild total-body hypothermia while anesthetized for a period of 24 hours reduces cerebral damage in our piglet survival model of global hypoxia-ischemia. Eighteen anesthetized piglets received a 45-minute global hypoxic-ischemic insult. The pigs were randomized either to remain normothermic or to receive SHC. We found that the severity of the hypoxic-ischemic insult was similar in the SHC versus the normothermic group, and that the mean neurology scores at 30 and 48 hours and neuropathology scores were significantly better in the SHC group versus the normothermic group. We conclude that selective head cooling combined with mild systemic hypothermia and anesthesia is neuroprotective when started immediately after the insult in our piglet model of hypoxic-ischemic encephalopathy.

Resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat

“…Therapeutic hypothermia (HT) has emerged as a neuroprotective therapy in both newborn animal models (2)(3)(4) and clinical trials (5-7). The collective evidence from these studies confirms that mild therapeutic HT improves outcome in hypoxic-ischemic encephalopathy, a condition in which ~50% of cooled infants normally die or have significant neurologic disability (8) as compared with before the advent of HT treatment when ~65% had poor outcome.…”

Minimal systemic hypothermia combined with selective head cooling evaluated in a pig model of hypoxia-ischemia

“…Instead, we found increased mortality in cooled animals and only a trend toward less subcortical white matter injury. In all previous studies with HT under sedation, we used 6-, 12-, or 24-h HT and found neuroprotection (8,18,19) but we chose 48-h SHC in this study to counteract minimal systemic HT. However, 48-h cooling was not tolerated by those animals suffering severe insults trending toward lower blood pressure and longer duration of inotropic support.…”

“…Reducing deep-brain temperature (T deep brain ) using SHC in term infants is difficult but may be easier in preterm infants with their smaller head size, thinner skin, and skull (5). In newborn pigs, T deep brain is within 1 °C of core temperature at normothermia (NT) but during SHC there is a gradient of between 3 and 7 °C (6)(7)(8)(9). SHC may offer an advantage over WBC because different brain regions may have different optimum temperatures for neuroprotection (9)(10)(11).…”

“…We showed previously that SHC combined with moderate systemic HT to 33.5 °C was neuroprotective using a global model of perinatal hypoxia-ischemia (HI) in the newborn pig (8). We hypothesized that minimal systemic HT (1.5 °C below core temperature) combined with SHC for 48 h would be neuroprotective compared with systemic NT using a validated neuropathology score.…”

Hypothermia for the treatment of infants with hypoxic–ischemic encephalopathy

“…25,26 Animal models of hypoxic-ischemic injury using fetal sheep, neonatal pigs and neonatal rats have shown benefits of hypothermia, including reduced neuronal loss, and improved survival and functional outcome. [27][28][29][30][31][32] Hypothermia is most effective if begun before the secondary phase of energy failure. These animal studies showed that the sooner cooling can be initiated after injury, the more likely it is to be successful.…”