Antioxidant Capacity of Proteins and Hydrolysates from the Liver of Newborn Piglets, and Their Inhibitory Effects on Steatosis in vitro.

RESEARCH BACKGROUND: Non-alcoholic steatohepatitis is a potentially progressive hepatic disorder that can lead to end-stage liver disease and hepatocellular carcinoma. The inhibitory effects of proteins and hydrolysates from the liver of newborn piglets on hepatic steatosis in oleic acid-induced hepatocellular carcinoma (HepG2) cells were investigated in vitro. EXPERIMENTAL APPROACH: The extracted proteins from the liver of newborn piglets were hydrolysed with papain, pepsin, trypsin and Alcalase. Based on the comparison of different enzyme digestion conditions, a protein hydrolysis protocol was established to obtain hydrolysates with lipid-lowering effect. RESULTS AND CONCLUSIONS: Trypsin-digested liver protein hydrolysate from newborn piglets exhibited strong antioxidant activity and good inhibitory effects against lipogenesis and cholesterol accumulation in HepG2 cells at the concentration of 150 µg/mL, with a triglyceride decrease of (43±3) % and cholesterol decrease of (31±5) %, compared with model group induced with 0.75 mM oleic acid. The addition of trypsin-digested liver protein hydrolysate from newborn piglets (300 µg/mL) decreased alanine aminotransferase and aspartate aminotransferase activities and increased superoxide dismutase activity. NOVELTY AND SCIENTIFIC CONTRIBUTION: This study demonstrated that the trypsin-digested liver protein hydrolysate from newborn piglets has a potential preventive effect against non-alcoholic fatty liver disease in its early stage, and a potential use as the modulator of lipid overaccumulation in form of food supplements.

Negative effects on newborn piglets caused by excess dietary tryptophan in the morning in sows.

BACKGROUND: This study investigated the effect of dynamic feeding models of dietary tryptophan on sows' performance during late pregnancy. RESULTS: The average piglet birth weight and live farrowing rate from sows consuming a high-low tryptophan diet (0.39% Trp in the morning and 0.13% Trp in the afternoon) were decreased compared with those fed a 2×tryptophan diet (0.26% Trp in the morning and afternoon). Compared with the 2×tryptophan group, sow serum kynurenic acid and the newborn liver n-6:n-3 polyunsaturated fatty acid ratio were significantly higher, and sow serum taurine and newborn serum taurine, phosphoserine, cysteine and proline were lower in the high-low tryptophan diet group. Eighty-eight genes were differentially expressed in newborn piglets' livers between the 2×tryptophan and high-low groups. Genes related to cytotoxic effector regulation (major histocompatibility complex class I proteins), NADH oxidation, reactive oxygen species (ROS) metabolism and tissue development were differentially expressed between these two groups. CONCLUSION: Together, the results provide information on new biomarkers in serum or liver and provide novel insights into variations in the fetal liver during exogenous stimulus response and biological processes of ROS metabolism in fetuses during late pregnancy caused by a single excessive tryptophan ingestion daily in the morning. © 2018 Society of Chemical Industry.

Co-occurrence of early gut colonization in neonatal piglets with microbiota in the maternal and surrounding delivery environments.

The early development of gut microbiota plays a fundamental role in host health; so far, the main origins of the first colonization in newborn piglets are largely unclear. This study aimed to investigate the early development of gut microbiota in newborn piglets during lactation and their co-occurrence with microbes in the maternal and surrounding environments by Illumina MiSeq sequencing of 16S ribosomal RNA genes. The results showed that the microbial richness and diversity in piglets' feces (PF) significantly increased from birth to weaning (21 d). The composition and function of microbiota in the feces of piglets after birth tended to be similar to those from the slatted floor (FL), sow's milk (SM) and nipple surface (SN), and lacter, the fecal microbial communities of piglets later during lactation were more similar to their mother's. SourceTracker analysis showed that the microbiota from the FL, SM and SN were most likely the earliest passengers to the neonatal gastrointestinal tract, but did not have a long stay during lactation. The sow's fecal microbiota were easier to colonize in newborn piglet's guts via the co-occurrence effect with former settlers. This study suggests that microbes from the maternal and surrounding environments may play an important role in the microbial succession of newborn piglets after birth.

Temporal Changes in Caspase-1 and Caspase-8 Activities Following Brain Hypoxia With and Without Src kinase Inhibition in a Piglet Animal Model.

The Src family kinases are a family of intracellular, non-receptor tyrosine kinases that are involved in a variety of cellular functions including the regulation of inflammation and apoptosis after brain hypoxia. Caspase-1 (C1) activates IL-1ß through the formation of complex structures, the inflammasomes, while caspase-8 (C8) is part of the extrinsic apoptotic pathway. C8 has been found to directly activate the production of IL-1ß. Previously, we observed that C1 and IL-1ß are increased in the acute phase after hypoxia in the brain of piglets, but they follow a different pattern long term, with C1 remaining activated throughout the period of observation, while IL-1ß returning to baseline at 15 days. Src kinase inhibition ameliorated the activation of C1 and IL-1ß early, but did not appear to have any effect long term. Prompted by these findings, we assessed the changes that occur over time (1 h and 15 days) in C1 and C8 activities after brain hypoxia as well as the effect of pretreatment with a Src kinase inhibitor, PP2 on these biochemical markers. Enzymatic activities were determined by spectrophotometry with measurements of C1 and C8 in each cytosolic brain sample (N = 4 in each group). We found that C1 and C8 activities increase in the acute phase following hypoxia in the brain of newborn piglets, with C8 relatively more than C1 (C8/C1 ratio increased from 2:1 as baseline to 3:1 in hypoxia). Fifteen days after hypoxia C8/C1 ratio decreased to about 1:1. In piglets that were pretreated with a Src kinase selective inhibitor (PP2) and then subjected to hypoxia, the C8/C1 ratio early increase was not observed. Immediately after hypoxia C8 and C1 follow a similar pattern of increase while long term this appears to dissociate. We propose that following this experimental methodology, the previously observed IL-1ß production after hypoxia might be associated with C8 rather than C1 and that Src kinase is involved in the above process.

Benefits of maternal pectin supplementation in gestation diet on vaginal microbiota of sows and intestinal health of newborn piglets.

Pectin is a proven prebiotic and widely used in human health products. This study aims to assess the impact of dietary pectin supplementation during gestation on sow vaginal microbiota and the offspring's intestinal composition. Thirty sows were randomly allocated to two groups and fed a standard diet (CON) or a standard diet supplemented with 3 g/kg pectin (PEC). Blood, feces, and vaginal swab samples from the sows and blood, intestines issue, and colonic content samples from the offspring were collected and analyzed. The results indicate that the relative abundance of vaginal Lactobacillus was notably enhanced in the PEC group and fecal ß-glucuronidase (ß-G) activity and plasma 17ß-estradiol (E2) concentration were also significantly increased in the PEC group. Newborn piglets were found to host different microbial communities as well. At the phylum level, Proteobacteria dominated in the CON group, and Firmicutes was predominant in the PEC group. Newborn piglets in the PEC group had a lower interleukin-6 (IL-6) concentration in their plasma. The expression of intestinal cytokines of offspring was improved as well. Villus height and villus height/crypt depth (V/C) in the PEC group were extremely higher than those in the CON group. In conclusion, dietary pectin supplementation can be of benefit to both sows and newborn piglets.

Disrupted Microbiota of Colon Results in Worse Immunity and Metabolism in Low-Birth-Weight Jinhua Newborn Piglets.

The Jinhua pig is well known in China due to its delicious meat. However, because of large litter size, low birth weight always happens. This experiment used this breed as a model to research bacterial evidence leading to growth restriction and provide a possible solution linked to probiotics. In this experiment, the differences in organs indexes, colonic morphology, short chain fatty acid (SCFA) concentrations, microbiome, and transcriptome were detected between piglets in the standard-birth-weight group (SG) and low-birth-weight group (LG) to find potential evidence leading to low birth weight. We found that LG piglets had a lower liver index (p < 0.05), deeper colonic crypt depth (p < 0.05), fewer goblet cells (p < 0.05), and more inflammatory factor infiltration. In addition, differentially expressed genes (DEGs) were mainly enriched in B-cell immunity and glucose metabolism, and LG piglets had lower concentrations of SCFAs, especially butyrate and isobutyrate (p < 0.05). Finally, most of the significantly differentially abundant microbes were fewer in LG piglets, which affected DEG expressions and SCFA concentrations further resulting in worse energy metabolism and immunity. In conclusion, colonic disrupted microbiota may cause worse glucose metabolism, immunity, and SCFA production in LG piglets, and beneficial microbes colonized in SG piglets may benefit these harmful changes.

Caffeine Administration in Piglets with Low Birthweight and Low Vitality Scores, and Its Effect on Physiological Blood Profile, Acid-Base Balance, Gas Exchange, and Infrared Thermal Response.

Intrapartum asphyxia, fetal hypoxia, and their consequences (e.g., acidosis, hypercapnia, hypoglycemia, and hypothermia) are the main factors related to physio-metabolic imbalances that increase neonatal mortality in piglets, particularly in piglets with low birthweight and low vitality scores. This study aimed to evaluate the effect of three different doses of caffeine (10, 20, and 30 mg/kg) administered orally to 480 newborn piglets with low birthweight and low vitality scores. Blood gas parameters (pH, pO2, pCO2, and HCO3-), physio-metabolic profile (Ca++, glucose, and lactate), and the thermal response assessed through infrared thermography in four thermal windows (ocular, auricular, snout, and hindlimb) and rectal temperature were evaluated during the first 24 h of life. Doses of 30 mg/kg resulted in significant differences at 24 h for all evaluated parameters, suggesting that caffeine administration improved the cardiorespiratory function and metabolic activity of piglets by reducing acidosis, restoring glycemia, and increasing surface and rectal temperature. In conclusion, caffeine at 30 mg/kg could be suggested as an appropriate dose to use in piglets with low birthweight and low vitality scores. Future research might need to study the presentation of adverse effects due to higher caffeine concentrations.

Effect of increasing dietary methionine-to-lysine ratio during early gestation on fetal development and piglet birth weight.

It was hypothesized that increasing dietary methionine (Met) for sows in early gestation would have a positive effect on fetal and placental growth and development, thereby also increasing the birth weight of piglets. The objective of the study was to investigate the effect of increasing the total dietary methionine-to-lysine ratio (Met:Lys) from 0.29 (Control diet) to 0.41 (Met diet) from mating to day 50 of gestation. A total of 349 multiparous sows were allocated to either the Control or Met diet group. The sows' backfat thickness was measured pre-farrowing, post-farrowing, and at weaning in the previous cycle and on days 14, 50 and 112 of gestation in the current cycle. On day 50, three Control and six Met sows were slaughtered. In 116 litters, piglets were weighed and measured individually at farrowing. The dietary treatment did not affect the sows' backfat thickness before or during gestation (P > 0.05). The number of liveborn and stillborn piglets at farrowing were similar in both groups (P > 0.05) and no differences in average piglet birth weight, total litter weight at birth or within-litter variation in birth weight (P > 0.05) were observed. In conclusion, increasing the dietary Met:Lys ratio for sows in early gestation had no effect on piglet birth weight.

Evaluation of post-colostrum ingestion changes in the protein composition of peripheral blood of newborn piglets: A pilot study.

Putatively, colostral proteins are partly absorbed and transferred to blood circulation in newborn piglets, which suggests that colostrum ingestion alters the protein composition of their blood. Here, we conducted a pilot study to estimate the changes in the protein composition of piglet blood. Plasma collected from piglets pre- and post-ingestion of colostrum (PreC and PostC) was analyzed by shotgun proteomics. Proteins in colostrum were also analyzed. We identified 393 and 427 proteins in PreC and PostC plasma, respectively, and 596 colostral proteins. Whereas 202 unique proteins were identified in PostC, PreC and PostC commonly shared 225 proteins. By contrast, when compared with PreC, 54 proteins in PostC had their emPAI values increased >2-fold. Notably, using plasma samples collected from a separate experiment, the concentrations of growth differentiation factor 8 and haptoglobin were higher in PostC than in PreC, which was validated by ELISA. Approximately 60% of the uniquely identified or highly concentrated proteins in PostC were also found in colostrum, which were likely, at least partly, transferred from colostrum. The present study demonstrated that the protein composition of plasma of newborn piglets drastically changed post-colostrum ingestion, partly due to transfer of colostral proteins.

Maternal nucleotide supplementation improves the intestinal morphology and immune function in lipopolysaccharide-challenged newborn piglets.

This study aimed to evaluate the effects of maternal nucleotide (NT) supplementation on intestinal morphology and immune function in lipopolysaccharide-challenged newborn piglets. At 85 d gestation, 12 sows were selected and assigned to two groups: the CON group (basal diet, n = 6) and the NT group (basal diet with 1 g/kg NT mixture, n = 6). After parturition, newborn piglets were collected without suckling. Piglets from the CON group were intraperitoneally injected with sterile saline or lipopolysaccharide (LPS, 10 mg/kg body weight), and divided into the C-CON (n = 6) and C-LPS groups (n = 6). Piglets from the NT group received the same treatment and were divided into the N-CON (n = 6) and N-LPS groups (n = 6). The blood and small intestinal samples of piglets were collected 1 h after injection. The results showed that: (1) maternal NT supplementation increased the concentrations of serum complement C3 and C4 (P < 0.05), and suppressed the increase in serum hypersensitive C-reactive protein in LPS-challenged newborn piglets (P < 0.05); (2) maternal NT supplementation increased the villus height and the ratio of villus height to crypt depth in the duodenum of newborn piglets (P < 0.05) and inhibited the LPS-induced decrease in the villus height in the jejunum and ileum (P < 0.05). (3) The LPS-induced increased levels of interleukin-6 in the jejunum and tumor necrosis factor-α in the ileum of newborn piglets were suppressed by maternal NT supplementation (P < 0.05). (4) In the jejunum of newborn piglets, maternal NT supplementation inhibited the LPS-induced increase in toll-like receptor 4 (TLR4) mRNA and protein expression (P < 0.05) and the decrease of nuclear factor-κB inhibitor α (IκBα) protein expression (P < 0.05). In the ileum, piglets had a lower nuclear factor-κB (NFκB) mRNA expression in the NT groups than the CON groups (P < 0.05), and maternal NT supplementation suppressed the decrease of IκBα mRNA in LPS-treated piglets (P < 0.05). In conclusion, maternal NT supplementation could promote the intestinal development and immune function of newborn piglets, and may improve LPS-induced intestinal inflammatory responses via the TLR4/IκBα/NFκB pathway.

Ventilation With or Without Endotracheal Tube Leak in Prolonged Neonatal Asphyxia.

Background Severe and prolonged asphyxia can result in either intrauterine fetal death and stillbirth or multiorgan failure in surviving neonates. Establishing effective ventilation is the primary aim of resuscitation in newborns with asphyxia. The objective of this study was to compare the outcome of resuscitation by applying an endotracheal tube (ETT) with less, an ETT with moderate, and an ETT with high leakage during mechanical ventilation in swine neonates after prolonged perinatal asphyxia. Materials and methods A prospective, randomized controlled laboratory study was performed. Thirty Landrace/large white pigs, aged one to four days and weighted 1.754±218 gr, were randomly allocated into three groups depending on the ETT size: Group C (less leak: ETT no 4.0, n=10); Group A (high leak: ETT no 3.0, n=10); and Group B (moderate leak: ETT no 3.5, n=10). Mechanical asphyxia was performed until their heart rate was less than 60 bpm or their mean arterial pressure was below 15 mmHg. All animals with return of spontaneous circulation (ROSC) were monitored for four hours for their hemodynamic parameters, arterial oxygen saturation, and lactate acid levels. Results We demonstrate that 70% of the surviving animals were ventilated with an ETT with a leak (no. 3.5 and 3). A statistically significant difference was noted in PO2 (p=0.032) between Group B (126.4±53.4 mmHg) compared to Group A (72.28±29.18 mmHg) and Group C (94.28±20.46 mmHg) as well as in the right atrial pressure (p<0.001) between Group C (4.5 mmHg) vs Groups A (2 mmHg) and B (2 mmHg) during ROSC time. Lactate levels were statistically significantly lower (p=0.035) in Group C (mean=0.92 ± 0.07mmol/L) as compared to Group A (mean=1.13 ± 0.1 mmol/L) and Group B (mean= 1.08 ± 0.07 mmol /L; p = 0.034) at 4h post-ROSC. Conclusion We provide preliminary evidence that ventilation with ETT with moderate leakage improves survival after 2h of ROSC, along with oxygenation and hemodynamic parameters, in a porcine model of neonatal asphyxia and resuscitation, compared to less leakage ETT.

Ventilation with 18, 21, or 100% Oxygen during Cardiopulmonary Resuscitation of Asphyxiated Piglets: A Randomized Controlled Animal Trial.

BACKGROUND: In previous piglet experiments of profound asphyxia and cardiac arrest, recovery was similar when 21 and 100% oxygen were used for positive pressure ventilation (PPV). There was no consistent reduction in inflammation and oxidative stress in piglets ventilated with 21 or 100% oxygen. OBJECTIVES: We aimed to investigate hypoxic resuscitation, i.e., PPV with 18% oxygen, in profoundly asphyxiated piglets with cardiac arrest. We hypothesized that resuscitation with 18% oxygen would result in less inflammation and oxidative stress compared to 21 or 100% oxygen. METHOD: Twenty-four piglets were exposed to 30 min of normocapnic hypoxia followed by asphyxia until asystole. The piglets were randomized to PPV with 18% oxygen (n = 8), 21% oxygen (n = 8), or 100% oxygen (n = 8), and resuscitated with chest compressions and intravenous epinephrine. Return of spontaneous circulation (ROSC) was defined as an unassisted heart rate ≥100 bpm for 15 s. Lactate, GSH (total glutathione), GSSG (oxidized glutathione), and GSSG/GSH ratio were measured in myocardial and frontoparietal cortex homogenates. Interleukin (IL)-8, IL-6, IL-1ß and tumor necrosis factor α were measured in frontoparietal cortex homogenates. RESULTS: There was no difference in time to ROSC or inflammation and oxidative stress in the 3 oxygen groups. CONCLUSIONS: Resuscitation with 18% oxygen did not result in differences in inflammation and oxidative stress when compared to 21 or 100% oxygen.

Learning Curves for Training in Ultrasonography-Based Examination of Umbilical Catheter Placement: A Piglet Study.

BACKGROUND: The training required for accurate assessment of umbilical catheter placement by ultrasonography (US) is unknown. OBJECTIVE: To describe the learning curve and provide an estimate of the accuracy of physicians' US examinations (US skills) and self-confidence when examining umbilical catheter tip placement. METHODS: Twenty-one physicians with minimal experience in US completed a 1.5-hour eLearning module. Ten piglets with catheters inserted in the umbilical vessels were used as training objects. Following eLearning each physician performed up to twelve 10-min US examinations of the piglets. Expert examinations were reference standards. Sensitivity and specificity of physicians' skills in detecting catheter tip placement by US was used to describe the learning curve. Self-confidence was reported by Likert scale after each examination. RESULTS: Physicians' detection of a correctly placed and misplaced umbilical artery catheter tip increased by an odds ratio of 1.6 (95% CI: 1.1, 2.3) and 3.6 (95% CI: 1.7, 7.8) per examination performed. A sensitivity of 0.97 (95% CI: 0.80, 0.99) and specificity of 0.95 (95% CI: 0.84, 0.99) was reached after 6 examinations. For the venous catheter, US skills in detecting a misplaced catheter tip increased with an odds ratio of 2.4 (95% CI: 1.2, 4.8) per US examination. Overall, performance and self-confidence plateaus were reached after 6 examinations. CONCLUSION: We found steep learning curves for targeted US examination of umbilical catheter placement. eLearning followed by 6 examinations was found to be adequate training to perform with a sufficiently high accuracy and self-confidence to allow for point-of-care use.

Sow environment during gestation: part II. Influence on piglet physiology and tissue maturity at birth.

Sow environment during gestation can generate maternal stress which could alter foetal development. The effects of two group-housing systems for gestating sows on piglet morphological and physiological traits at birth were investigated. During gestation, sows were reared in a conventional system on a slatted floor (C, 18 sows), demonstrated as being stressful for sows or in an enriched system in larger pens and on deep straw bedding (E, 19 sows). On gestation day 105, sows were transferred into identical individual farrowing crates on a slatted floor. Farrowing was supervised to allow sampling from piglets at birth. In each litter, one male piglet of average birth weight was euthanized immediately after birth to study organ development and tissue traits. Blood samples were collected from 6 or 7 piglets per litter at birth and 2 piglets per litter at 4 days of lactation (DL4). At birth, mean piglet BW did not differ between groups (P > 0.10); however, the percentage of light ( 0.10) between C and E piglets, but the insulin to glucose ratio was greater (P = 0.02) in C than in E piglets. Compared with E piglets, C piglets had a lighter gut at birth (P = 0.01) and their glycogen content in longissimus muscle was lower (P < 0.01). In this muscle, messenger RNA levels of PAX7, a marker of satellite cells and of PPARGC1A, a transcriptional coactivator involved in mitochondriogenesis and mitochondrial energy metabolism, were greater (P < 0.05), whereas the expression level of PRDX6, a gene playing a role in antioxidant pathway, was lower (P = 0.03) in C than in E piglets. Other studied genes involved in myogenesis did not differ between C and E piglets. No system effect was observed on target genes in liver and subcutaneous adipose tissue. On DL4, C piglets exhibited a lower plasma antioxidant capacity than E piglets (P = 0.002). In conclusion, exposure of sows to a stressful environment during gestation had mild negative effects on the maturity of piglets at birth.

Biomarker Discovery by Mass Spectrometry in Cerebrospinal Fluid and Plasma after Global Hypoxia-Ischemia in Newborn Piglets.

BACKGROUND: Biomarkers may qualify diagnosis, treatment allocation, and prognostication in neonatal encephalopathy. Biomarker development is challenged by competing etiologies, inter-individual genetic variability, and a lack of specific neonatal markers. To address these challenges, we used a standardized neonatal hypoxic-ischemic (HI) encephalopathy model with pre- and post-HI sampling of cerebrospinal fluid (CSF) and plasma. OBJECTIVES: The study aimed to identify novel candidate protein biomarkers of HI encephalopathy in a newborn piglet model in CSF and plasma. METHODS: FiO2 was lowered to 4% in 6 newborn piglets, then adjusted over a 45-min period keeping the amplitude integrated-EEG < 7 µV to induce HI encephalopathy. CSF and plasma was sampled pre-HI and 2 h after HI, protein levels were then analyzed by mass spectrometry. RESULTS: Protein levels after HI changed significantly for 18 CSF proteins and 37 plasma proteins. CSF and plasma data showed distinct information, although peptidyl-prolyl cis-trans isomerase A had elevated levels in both fluids. HI regulation involved functional groups such as the antioxidant system, cell proliferation, cell structure, and apoptosis. S100-A8, which increased the most in CSF (9.5 fold), is known to be involved in inflammatory and immune response and to be highly regulated during injury. In plasma, increased proteins included FABP1 (31.8 fold) and proteins with antioxidant (SOD1, GPX3) and lectin function (REG3A, LGALS3). CONCLUSIONS: In this exploratory study, we have identified candidate biomarkers for HI in CSF and plasma, many not previously associated with HI. Identified proteins are promising candidates for further validation in time series experiments and clinical studies.

High-Dose Cannabidiol Induced Hypotension after Global Hypoxia-Ischemia in Piglets.

BACKGROUND: Cannabidiol (CBD) is considered a promising neuroprotectant after perinatal hypoxia-ischemia (HI). We have previously studied the effects of CBD 1 mg/kg in the early phase after global HI in piglets. In contrast to prior studies, we found no evidence of neuroprotection and hypothesized that higher doses might be required to demonstrate efficacy in this animal model. OBJECTIVE: To assess the safety and potential neuroprotective effects of high-dose CBD. METHODS: Anesthetized newborn piglets underwent global HI by ventilation with 8% O2 until the point of severe metabolic acidosis (base excess -20 mmol/L) and/or hypotension (mean arterial blood pressure ≤20 mm Hg). Piglets were randomized to intravenous treatment with vehicle (n = 9) or CBD (n = 13). The starting dose, CBD 50 mg/kg, was reduced if adverse effects occurred. The piglets were euthanized 9.5 h after HI and tissue was collected for analysis. RESULTS: CBD 50 mg/kg (n = 4) induced significant hypotension in 2 out of 4 piglets, and 1 out of 4 piglets suffered a fatal cardiac arrest. CBD 25 mg/kg (n = 4) induced significant hypotension in 1 out of 4 piglets, while 10 mg/kg (n = 5) was well tolerated. A significant negative correlation between the plasma concentration of CBD and hypotension during drug infusion was observed (p < 0.005). Neuroprotective effects were evaluated in piglets that did not display significant hypotension (n = 9) and CBD did not alter the degree of neuronal damage as measured by a neuropathology score, levels of the astrocytic marker S100B in CSF, magnetic resonance spectroscopy markers (Lac/NAA and Glu/NAA ratios), or plasma troponin T. CONCLUSIONS: High-dose CBD can induce severe hypotension and did not offer neuroprotection in the early phase after global HI in piglets.

Hypoxia/reoxygenation-induced myocardial lesions in newborn piglets are related to interindividual variability and not to oxygen concentration

OBJECTIVE: Evaluation of myocardial histological changes in an experimental animal model of neonatal hypoxiareoxygenation. METHODS: Normocapnic hypoxia was induced in 40 male Landrace/Large White piglets. Reoxygenation was initiated when the animals developed bradycardia (HR <60 beats/min) or severe hypotension (MAP <15 mmHg). The animals were divided into four groups based on the oxygen (O2) concentration used for reoxygenation; groups 1, 2, 3, and 4 received 18%, 21%, 40%, and 100% O2, respectively. The animals were further classified into five groups based on the time required for reoxygenation: A: fast recovery (<15 min); B: medium recovery (15-45 min); C: slow recovery (45-90 min); D: very slow recovery (>90 min), and E: nine deceased piglets. RESULTS: Histology revealed changes in all heart specimens. Interstitial edema, a wavy arrangement, hypereosinophilia and coagulative necrosis of cardiomyocytes were observed frequently. No differences in the incidence of changes were observed among groups 1-4, whereas marked differences regarding the frequency and the degree of changes were found among groups A-E. Coagulative necrosis was correlated with increased recovery time: this condition was detected post-asphyxia in 14%, 57%, and 100% of piglets with fast, medium, and slow or very slow recovery rates, respectively. CONCLUSIONS: The significant myocardial histological changes observed suggest that this experimental model might be a reliable model for investigating human neonatal cardiac hypoxia-related injury. No correlation was observed between the severity of histological changes and the fiO2 used during reoxygenation. Severe myocardial changes correlated strictly with recovery time, suggesting an unreported individual susceptibility of myocardiocytes to hypoxia, possibly leading to death after the typical time-sequence of events.