Neuroprotection provided by hypothermia initiated with high transnasal flow with ambient air in a model of pediatric cardiac arrest.

Clinical trials of hypothermia after pediatric cardiac arrest (CA) have not seen robust improvement in functional outcome, possibly because of the long delay in achieving target temperature. Previous work in infant piglets showed that high nasal airflow, which induces evaporative cooling in the nasal mucosa, reduced regional brain temperature uniformly in half the time needed to reduce body temperature. Here, we evaluated whether initiation of hypothermia with high transnasal airflow provides neuroprotection without adverse effects in the setting of asphyxic CA.

Use of an end-tidal carbon dioxide-guided algorithm during cardiopulmonary resuscitation improves short-term survival in paediatric swine.

Aim: To evaluate an algorithm that uses an end-tidal carbon dioxide (ETCO) target of ≥ 30 torr to guide specific changes in chest compression rate and epinephrine administration during cardiopulmonary resuscitation (CPR) in paediatric swine.

Methods: Swine underwent asphyxial cardiac arrest followed by resuscitation with either standard or ETCO-guided algorithm CPR. The standard group received chest compressions at a rate of 100/min and epinephrine every 4 min during advanced life support consistent with the American Heart Association paediatric resuscitation guidelines.

Combining Hypothermia and Oleuropein Subacutely Protects Subcortical White Matter in a Swine Model of Neonatal Hypoxic-Ischemic Encephalopathy.

Neonatal hypoxia-ischemia (HI) causes white matter injury that is not fully prevented by therapeutic hypothermia. Adjuvant treatments are needed. We compared myelination in different piglet white matter regions.

Neurologic effects of short-term treatment with a soluble epoxide hydrolase inhibitor after cardiac arrest in pediatric swine.

Background: Cardiac arrest (CA) is the most common cause of acute neurologic insult in children. Many survivors have significant neurocognitive deficits at 1 year of recovery. Epoxyeicosatrienoic acids (EETs) are multifunctional endogenous lipid signaling molecules that are involved in brain pathobiology and may be therapeutically relevant.

Mean Diffusivity in Striatum Correlates With Acute Neuronal Death but Not Lesser Neuronal Injury in a Pilot Study of Neonatal Piglets With Encephalopathy.

Background: Diffusion MRI is routinely used to evaluate brain injury in neonatal encephalopathy. Although abnormal mean diffusivity (MD) is often attributed to cytotoxic edema, the specific contribution from neuronal pathology is unclear.

Purpose: To determine whether MD from high-resolution diffusion tensor imaging (DTI) can detect variable degrees of neuronal degeneration and pathology in piglets with brain injury induced by excitotoxicity or global hypoxia-ischemia (HI) with or without overt infarction.

Association of diastolic blood pressure with survival during paediatric cardiopulmonary resuscitation.

Aim: To examine the relationship between survival and diastolic blood pressure (DBP) throughout resuscitation from paediatric asphyxial cardiac arrest.

Methods: Retrospective, secondary analysis of 200 swine resuscitations. Swine underwent asphyxial cardiac arrest and were resuscitated with predefined periods of basic and advanced life support (BLS and ALS, respectively).

The Effect of Asphyxia Arrest Duration on a Pediatric End-Tidal CO2-Guided Chest Compression Delivery Model.

Objectives: To determine the effect of the duration of asphyxial arrest on the survival benefit previously seen with end-tidal CO2-guided chest compression delivery.

Design: Preclinical randomized controlled study.

Setting: University animal research laboratory.

Hypoxia-Ischemia and Hypothermia Independently and Interactively Affect Neuronal Pathology in Neonatal Piglets with Short-Term Recovery.

Therapeutic hypothermia is the standard of clinical care for moderate neonatal hypoxic-ischemic encephalopathy. We investigated the independent and interactive effects of hypoxia-ischemia (HI) and temperature on neuronal survival and injury in basal ganglia and cerebral cortex in neonatal piglets. Male piglets were randomized to receive HI injury or sham procedure followed by 29 h of normothermia, sustained hypothermia induced at 2 h, or hypothermia with rewarming during fentanyl-nitrous oxide anesthesia.

Spatial T-maze identifies cognitive deficits in piglets 1 month after hypoxia-ischemia in a model of hippocampal pyramidal neuron loss and interneuron attrition.

Neonatal brain injury from hypoxia-ischemia (HI) causes major morbidity. Piglet HI is an established method for testing neuroprotective treatments in large, gyrencephalic brain. Though many neurobehavior tests exist for rodents, such tests and their associations with neuropathologic injury remain underdeveloped and underutilized in large, neonatal HI animal models.

Pilot Study to Compare the Use of End-Tidal Carbon Dioxide-Guided and Diastolic Blood Pressure-Guided Chest Compression Delivery in a Swine Model of Neonatal Asphyxial Cardiac Arrest.

Background The American Heart Association recommends use of physiologic feedback when available to optimize chest compression delivery. We compared hemodynamic parameters during cardiopulmonary resuscitation in which either end-tidal carbon dioxide ( ETCO ) or diastolic blood pressure ( DBP ) levels were used to guide chest compression delivery after asphyxial cardiac arrest. Methods and Results One- to 2-week-old swine underwent a 17-minute asphyxial-fibrillatory cardiac arrest followed by alternating 2-minute periods of ETCO -guided and DBP -guided chest compressions during 10 minutes of basic life support and 10 minutes of advanced life support.

Proteasome Biology Is Compromised in White Matter After Asphyxic Cardiac Arrest in Neonatal Piglets.

Background Neurological deficits in hypoxic-ischemic encephalopathy, even with therapeutic hypothermia, are partially attributed to white matter injury. We theorized that proteasome insufficiency contributes to white matter injury. Methods and Results Neonatal piglets received hypoxia-ischemia ( HI ) or sham procedure with normothermia, hypothermia, or hypothermia+rewarming.

d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study.

The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be "unnatural", have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in the hippocampus, cortex, and blood samples from NIH Swiss mice are reported.

Hypothermia and Rewarming Activate a Macroglial Unfolded Protein Response Independent of Hypoxic-Ischemic Brain Injury in Neonatal Piglets.

Therapeutic hypothermia provides incomplete neuroprotection after hypoxia-ischemia (HI)-induced brain injury in neonates. We previously showed that cortical neuron and white matter apoptosis are promoted by hypothermia and early rewarming in a piglet model of HI. The unfolded protein response (UPR) may be one of the potential mediators of this cell death.