Effects of Xenon and Hypothermia on Cerebrovascular Pressure Reactivity in Newborn Global Hypoxic—ischemic Pig Model

Abstract

Autoregulation of cerebral perfusion is impaired in hypoxic-ischemic encephalopathy. We investigated whether cerebrovascular pressure reactivity (PRx), an element of cerebral autoregulation that is calculated as a moving correlation coefficient between averages of intracranial and mean arterial blood pressure (MABP) with values between À 1 and þ 1, is impaired during and after a hypoxic-ischemic insult (HI) in newborn pigs. Associations between end-tidal CO 2 , seizures, neuropathology, and PRx were investigated. The effect of hypothermia (HT) and Xenon (Xe) on PRx was studied. Pigs were randomized to Sham, and after HI to normothermia (NT), HT, Xe or xenon hypothermia (XeHT). We defined PRx 40.2 as peak and negative PRx as preserved. Neuropathology scores after 72 hours of survival was grouped as 'severe' or 'mild.' Secondary PRx peak during recovery, predictive of severe neuropathology and associated with insult severity (P ¼ 0.05), was delayed in HT (11.5 hours) than in NT (6.5 hours) groups. Seizures were associated with impaired PRx in NT pigs (P ¼ 0.0002), but not in the HT/XeHT pigs. PRx was preserved during normocapnia and impaired during hypocapnia. Xenon abolished the secondary PRx peak, increased (mean (95% confidence interval (CI)) MABP (6.5 (3.8, 9.4) mm Hg) and cerebral perfusion pressure (5.9 (2.9, 8.9) mm Hg) and preserved the PRx (regression coefficient, À 0.098 (95% CI ( À 0.18, À 0.01)), independent of the insult severity.

Pathophysiology of Cerebral Hyperperfusion in Term Neonates With Hypoxic-Ischemic Encephalopathy: A Systematic Review for Future Research

“…The study of Chakkarapani et al ( 24 ) investigated cerebral perfusion by using cerebrovascular pressure reactivity (PRx). In this study, PRx was shown to be impaired during and after a H-I event.…”

“…Cerebral hyperperfusion seen in term neonates with hypoxic-ischemic encephalopathy (HIE) has been correlated with an adverse neurodevelopmental outcome ( 2 , 9 , 22 – 24 ). In order to understand how cerebral hyperperfusion is correlated with an adverse outcome, we must understand the pathophysiology.…”

Xenon Combined with Therapeutic Hypothermia Is Not Neuroprotective after Severe Hypoxia-Ischemia in Neonatal Rats

“…Importantly, in contrast to high-affinity NMDA receptor antagonists, Xe does not appear to have any neurotoxic effects [ 23 ]. When administered at a sub-anesthetic dosage (50%), Xe also stabilises blood pressure and cardiac output and reduces the need for inotropes [ 9 ]. This might be partly due to increased neuronal norepinephrine levels as a result of Xe-mediated antagonism of norepinephrine reuptake [ 24 ].…”

“…The anesthetic gas xenon (Xe) has been shown to double neuroprotection after moderate hypoxic-ischemic (HI) brain injury in newborn animal models when combined with TH [ 6 – 8 ]. When inhaled in a sub-anesthetic dosage of 50%, Xe is both neuroprotective and stabilizes the blood pressure and cerebrovascular reactivity [ 7 , 9 ]. Due to the additive neuroprotective effect of TH+Xe after moderate experimental HI seen after both short (1 week) [ 10 ]and long term (adulthood) survival [ 6 , 7 , 11 ], TH and Xe is a promising combination treatment for infants with severe hypoxic brain injury.…”

Hypoxic-Ischemic Encephalopathy in Neonates Born to Severe Birth Asphyxia

“…Применение гипотермии с ксеноном у новорож-дённых свиней после эпизода ишемии-гипоксии, улучшает мозговую ауторегуляцию после повреж-дения [14].…”