DOI: 10.5061/dryad.4tmpg4fkd
title: Data from: Neuroprotection provided by hypothermia initiated with high transnasal flow with ambient air in a model of pediatric cardiac arrest

description: Clinical trials of hypothermia after pediatric cardiac arrest 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. The mouth is kept open to
 allow the high nasal airflow to easily exit. Here, we evaluated whether
 initiation of hypothermia with high transnasal airflow (32 L/min) provides
 neuroprotection without adverse effects in the setting of asphyxic cardiac
 arrest. Anesthetized, mechanically ventilated piglets (approximately
 2-weeks-old) underwent sham-operated procedures (Group 1) or asphyxic
 cardiac arrest (Groups 2-6). The asphyxic insult consisted of reducing the
 inspired oxygen from 30% to 9.5-10% for 45 minutes (hypoxia period), then
 briefly increasing the inspired oxygen to 21% for 5 min (to improve the
 later success of cardiac resuscitation), and then completely stopping
 ventilation for 7 minutes. Cardiopulmonary resuscitation (CPR) commenced
 by re-establishing ventilation, performing chest compression, and
 injecting epinephrine as needed. The five cardiac arrest groups were
 further divided into those with normothermic recovery (38.5°C; Group 2),
 with mild hypothermia (34°C) initiated by surface cooling at 10 minutes
 (Group 3) or 120 minutes (Group 5) after resuscitation, or with mild
 hypothermia (34°C) initiated by transnasal cooling initiated at 10 minutes
 (Group 4) or 120 minutes (Group 6) after resuscitation. In the two
 transnasal cooling groups, the high nasal airflow continued for 2 hours
 and was then stopped; thereafter, surface cooling was used to maintain
 hypothermia. In all four groups with induced hypothermia, rectal
 temperature was sustained at the targeted temperature of 34°C with surface
 cooling until 20 hours after resuscitation, followed by 6 hours of gradual
 rewarming and cessation of fentanyl/70% nitrous oxide anesthesia. At four
 days of recovery, the piglets were euthanized and their brains were
 analyzed for the density of morphologically intact neurons in putamen,
 sensorimotor cortex, ventrolateral thalamus, and prefrontal cortex. The
 data sheet shows the density of viable neurons in these 4 brain regions
 for the 45 piglets that completed the study. The data sheet also shows the
 serial measurements of rectal temperature, mean arterial blood pressure,
 heart rate, and arterial blood measurements of the partial pressure of
 oxygen (PO2) and carbon dioxide (PCO2), oxyhemoglobin saturation, and pH
 obtained at baseline, during the period of hypoxia, at 4 minutes of
 ventilation with 21% O2, during the period of asphyxia, and during the
 first 24 hours of recovery. The piglets are assigned the same unique
 identifier number, labelled 1-45, for each set of measurements. Transnasal
 cooling initiated at 10 minutes after resuscitation was able to
 significantly rescue neurons in the highly vulnerable putamen without
 adverse effects.
description: Body temperature was measured with a rectal
 thermometer. Arterial pressure was measured with a
 pressure transducer connected to a fluid-filled catheter in the femoral
 artery. Heart rate was derived from the frequency of
 the arterial pressure pulses. Blood
 samples were periodically drawn from the femoral artery and analyzed for
 pH, PCO2, PO2, oxyhemoglobin saturation, and hemoglobin concentration on a
 Radiometer ABL800 Flex blood gas analyzer, with values corrected for body
 temperature. For histopathology, deeply anesthetized
 piglets underwent transcardial perfusion with cold phosphate-buffered
 saline, followed by ice-cold 4% paraformaldehyde. The brains were
 post-fixed overnight, then carefully removed from the skull. Each brain
 was bisected along the mid-sagittal plane and sectioned into a 20-mm
 coronal slab, ranging from -2 to +18 mm from the bregma. This process
 ensured the inclusion of key areas: the basal ganglia, sensorimotor
 cortex, and thalamus. The slab was further divided into three slices, with
 an additional slice reserved for the prefrontal cortex, and all sections
 were embedded in paraffin. For histological analysis, 10-μm sections were
 stained with hematoxylin and eosin. The examination was conducted under
 oil immersion at 1000× magnification by a researcher blinded to the
 treatment details. Viable neurons were identified as round or oval cell
 bodies with a thin rim of cytoplasm, an open nucleus, and evident
 nucleolus. Neurons were considered to have an ischemic morphology if they
 had a shrunken, pyknotic nucleus with eosinophilic cytoplasm. Neuron
 counts were obtained in seven nonoverlapping fields in the putamen and in
 nine nonoverlapping fields per slide in layers II-VI of the sensorimotor
 cortical gyrus. Three slides representing the entire length of the putamen
 were used. A similar process was applied to the prefrontal cortex, where
 neurons were counted in nine nonoverlapping fields on the para-sagittal
 cortical gyrus. Additionally, in the most caudal block, viable neurons in
 the ventrolateral posterior thalamus were counted in seven distinct
 fields. Data are presented as the number of neurons with a viable
 morphology per mm^2 area.
description: # Neuroprotection provided by hypothermia initiated with high transnasal
 flow with ambient air in a model of pediatric cardiac arrest This study
 examined whether two techniques for inducing therapeutic hypothermia
 (standard body surface cooling and a novel technique in which high airflow
 through the nostrils to produce evaporative cooling of blood draining the
 nasal mucosa) after resuscitation from hypoxic-asphyxic cardiac arrest
 improves the survival of neurons in four brain regions (putamen,
 sensorimotor cortex, thalamus, and prefrontal cortex) in an infant swine
 model. For each cooling technique, separate groups were studied in which
 cooling commenced at either 10 or 120 minutes after resuscitation. The
 trial had 6 arms: Group 1 = Sham surgery and anesthesia Group 2 = Cardiac
 arrest + normothermia recovery Group 3 = Cardiac arrest + surface cooling
 from 10 minutes through 20 hours Group 4 = Cardiac arrest + transnasal
 cooling from 10 minutes through 120 minutes followed by surface cooling
 from 120 minutes through 20 hours through 20 hours Group 5 = Cardiac
 arrest + surface cooling from 120 minutes through 20 hours Group 6 =
 Cardiac arrest + transnasal cooling from 120 minutes through 240 minutes
 followed by surface cooling from 240 minutes through 20 hours For each
 particular measurement domain (neuronal counts, rectal temperature, mean
 arterial blood pressure, heart rate, and arterial blood measurements of
 the partial pressure of oxygen (PO2) and carbon dioxide (PCO2), percent
 oxyhemoglobin saturation, and pH), the datasheet is structured such that
 repeated measurements from the same subject appear in multiple columns
 across the same row. For histological measurements, different columns
 represent different brain regions, as indicated by the column headings
 putamen, sensorimotor cortex, thalamus, and prefrontal cortex. For
 physiologic measurements, different columns represent measurements taken
 at different times during the protocol. The column headings define the
 times during the periods of hypoxia, asphyxia, and the first 24 hours of
 recovery (including the first 4 hours of slow rewarming in the hypothermic
 groups). For each type of measurement, a new set of rows are made rows for
 each subject (the same animal will appear on different rows for each type
 of measurement). The same unique animal identification number (ranging
 from 1 to 45) is used for each type of measurement. The 6 treatment arms
 are denoted in the column with the heading Group (numbered 1-6). Missing
 data are denoted with blanks.