The Aeromedical Management of Allergic Rhinitis.

INTRODUCTION: Allergic rhinitis is a prevalent condition warranting special aeromedical consideration due to its potential for acute and painful manifestations involving the middle ear or paranasal sinuses during rapid barometric pressure changes. Although second generation antihistamines and intranasal steroids are safe and effective treatments for this common condition, aeromedical management varies. METHODS: An aeromedical policy review of 14 public access civil and military data repositories was undertaken. Policy within a convenience sample of nine countries (Australia, Canada, Croatia, France, New Zealand, Norway, Sweden, United Kingdom, and United States) was further ascertained through subject matter expert consultation. A convenience sample of recent primary care review articles and ENT guidelines were reviewed in order to substantiate the evidence basis for aeromedical practices. RESULTS: Policies range from disqualification of flight applicants with any history of allergic rhinitis to the authorization of short-term, select undeclared medication use for the management of mild symptoms, with military authorities applying a more conservative approach. A range of intranasal and oral therapies are approved and requirements for waiver vary across most authorities. DISCUSSION: Variation in practices must be considered when managing flight crews as part of military coalition peacetime and combat operations, as well as for international civil aviation missions conducted in support of natural disaster relief, rescue, and other stability efforts. Standardization of approved therapies for allergic rhinitis could be a useful starting point for the harmonization of aeromedical global policies in the future. Beneficial national specific policy updates may be undertaken on the basis of international experience.Powell-Dunford N, Reese C, Bushby A, Munkeby BH, Coste S, Pezer VL, Rosenkvist L. The aeromedical management of allergic rhinitis. Aerosp Med Hum Perform. 2018; 89(5):453-463.

Contrast-enhanced ultrasound identifies reduced overall and regional renal perfusion during global hypoxia in piglets.

OBJECTIVE: It is well known from both clinical experience and animal research that renal hypoxia may lead to temporary or permanent renal failure, the severity being dependent largely on the duration and grade of the hypoxia. The medulla is more susceptible to hypoxic injury than the cortex because approximately 90% of the renal blood flow supplies the cortex. Various methods have been applied to evaluate renal perfusion in both experimental and clinical settings, including magnetic resonance imaging, computed tomography, laser Doppler, and contrast-enhanced ultrasound (CEUS). PURPOSE: The aim of this study was to evaluate changes in overall and regional renal perfusion with CEUS in response to global hypoxia. MATERIAL AND METHODS: Twelve newborn anesthetized piglets were exposed to general hypoxia with a fraction of inspired oxygen of 8% of 30 minutes duration. Resuscitation was performed with either 100% oxygen (n = 6) or air (21% oxygen) (n = 6) for 30 minutes followed by 7 hours of reoxygenation with air. Before, during, and after hypoxia, the left kidney was examined with CEUS using 0.2 mL IV of SonoVue followed by 2 mL saline flush. Five additional piglets served as controls. The kidney was examined using a 9-MHz linear transducer with low mechanical index (0.21) and pulse inversion contrast program. One region of interest was drawn in the renal cortex and 1 in the medulla to obtain the corresponding time intensity curves (TICs). From these curves, the peak intensity (PI), time to peak (TTP), upslope of the curve, area under the curve, and mean transit time (MTT) were recorded. Also, the renal arteriovenous transit time (AVTT) was registered. The resistance index (RI) was repeatedly measured in the renal artery. Contrast-enhanced ultrasound was repeated at regular intervals until the animals were sacrificed 8 hours after the hypoxic period. RESULTS: In the group of 12 piglets subjected to hypoxia, RI increased from 0.69 ± 0.08 at baseline to 0.99 ± 0.09 during hypoxia (P < 0.01), indicating severe general renal vasoconstriction. The AVTT increased from 2.6 ± 0.5 seconds at baseline to 6.7 ± 2.8 seconds during hypoxia (P < 0.001). The PI in the cortex decreased from a mean value of 38.6 ± 6.1 dB at baseline to 30.3 ± 9.7 dB during hypoxia (P < 0.05). In the medulla, only a minor, nonsignificant reduction in PI was observed during hypoxia. In the medulla, TTP and MTT increased from 6.4 ± 1.5 and 9.2 ± 1.7 seconds at baseline to 14.6 ± 8.4 seconds (P < 0.01) and 15.2 ± 5.6 seconds (P < 0.01), respectively, during hypoxia. In the cortex, no statistically significant changes in TTP or MTT were observed during hypoxia. A return to near-baseline values was observed for TTP, PI in both the medulla and cortex, as well as for RI and AVTT within 1 to 3 hours after hypoxia, and they remained relatively constant for the duration of the experiment.Less than 1 hour after the hypoxia, PI both in the cortex and the medulla was significantly higher in the group resuscitated with air than in the group resuscitated with 100% oxygen, 36.0 ± 4.3 versus 27.2 ± 2.2 dB (P < 0.05) and 33.3 ± 8.2 versus 21.1 ± 2.0 dB (P < 0.01), respectively. CONCLUSION: Global hypoxia induced changes in overall and regional renal perfusion detectable with CEUS. Cortical and medullary flows were affected differently by hypoxia; a strong increase in medullary TTP and MTT was observed, indicating a reduction in medullary blood flow velocity. In the cortex, a significant reduction in PI was found, probably because of a reduction in cortical blood volume. A faster recovery of both medullary and cortical PI in the group resuscitated with air could indicate that air might be more beneficial for renal perfusion than hyperoxia during resuscitation after renal hypoxia.

Dynamic FDG PET for assessing early effects of cerebral hypoxia and resuscitation in new-born pigs.

PURPOSE: Changes in cerebral glucose metabolism may be an early prognostic indicator of perinatal hypoxic-ischaemic injury. In this study dynamic ¹8F-FDG PET was used to evaluate cerebral glucose metabolism in piglets after global perinatal hypoxia and the impact of the resuscitation strategy using room air or hyperoxia. METHODS: New-born piglets (n = 16) underwent 60 min of global hypoxia followed by 30 min of resuscitation with a fraction of inspired oxygen (FiO2) of 0.21 or 1.0. Dynamic FDG PET, using a microPET system, was performed at baseline and repeated at the end of resuscitation under stabilized haemodynamic conditions. MRI at 3 T was performed for anatomic correlation. Global and regional cerebral metabolic rates of glucose (CMRgl) were assessed by Patlak analysis for the two time-points and resuscitation groups. RESULTS: Global hypoxia was found to cause an immediate decrease in cerebral glucose metabolism from a baseline level (mean ± SD) of 21.2 ± 7.9 to 12.6 ± 4.7 µmol/min/ 100 g (p <0.01). The basal ganglia, cerebellum and cortex showed the greatest decrease in CMRgl but no significant differences in global or regional CMRgl between the resuscitation groups were found. CONCLUSION: Dynamic FDG PET detected decreased cerebral glucose metabolism early after perinatal hypoxia in piglets. The decrease in CMRgl may indicate early changes of mild cerebral hypoxia-ischaemia. No significant effect of hyperoxic resuscitation on the degree of hypometabolism was found in this early phase after hypoxia. Cerebral FDG PET can provide new insights into mechanisms of perinatal hypoxic- ischaemic injury where early detection plays an important role in instituting therapy.

Cerebral perfusion in perinatal hypoxia and resuscitation assessed by transcranial contrast-enhanced ultrasound and 3 T MRI in newborn pigs.

OBJECTIVE: Cerebrovascular factors are crucially involved in the early injury after perinatal asphyxia. With magnetic resonance imaging (MRI) and ultrasonography (US), this study aimed to quantify microvascular perfusion changes due to hypoxia and resuscitation, by comparing contrast-enhanced ultrasound (CEUS) to dynamic susceptibility contrast-enhanced (DSC)-MRI and diffusion-weighted MRI. MATERIAL AND METHODS: Newborn piglets (n = 12/17) were reoxygenated with 21% (n = 6) or 100% O2 (n = 6) after global hypoxia. Five piglets served as controls. CEUS and MRI were performed before, during, and up to 7 hours after hypoxia. Following are the perfusion parameters for CEUS: peak intensity (PI), area under the curve (AUC), time to peak (TTP), and upslope a and perfusion/diffusion parameters for MRI: relative cerebral blood volume, relative cerebral blood flow, mean transit time, and apparent diffusion coefficient were compared between different regions in the brain across time points and also compared with histology at the end. RESULTS: In CEUS, compared with the control group, perfusion changed significantly over time, in the hyperoxic group in all regions for PI, AUC in all regions of interests. The changes presented mainly as decreased perfusion during and shortly after resuscitation: for PI in the basal ganglia (BG), cortex, and the whole brain with 50 to 60% (P ≤ 0.001); for AUC in the BG and cortex with 90% (P ≤ 0.02) and in the whole brain with 70% (P = 0.004). In the injured brains (confirmed by histology), significant changes over time were seen in TTP and AUC with mainly increased perfusion during hypoxia: for TTP in the cortex, AUC in the BG and whole brain with 90 to 100% (P ≤ 0.04), and for TTP in the whole brain with 50% (P = 0.02). DSC-MRI showed the same trends in perfusion with regard to relative cerebral blood volume as CEUS. In all pigs exposed to hypoxia, perfusion returned toward baseline values at 7 hours after hypoxia in both methods. Apparent diffusion coefficient decreased significantly after 7 hours in the injured brains in the BG from 114.6 ± 1.2 × 10mm/s to 90.3 ± 24 × 10 mm/s (P = 0.03). CONCLUSIONS: CEUS and DSC-MRI can detect an early temporal evolution of cerebral perfusion in perinatal hypoxia and resuscitation, reversible after 7 hours. Hyperoxic resuscitation caused early decreased cerebral perfusion, not present in the normoxic group. The combined use of CEUS and DSC-MRI can provide important diagnostic information and give new insights into perinatal vascular hypoxia mechanisms.

Ejection time-corrected systolic velocity improves accuracy in the evaluation of myocardial dysfunction: a study in piglets.

This study aimed to assess the effect of correcting for the impact of heart rate (HR) or ejection time (ET) on myocardial velocities in the long axis in piglets undergoing hypoxia. The ability to eject a higher volume at a fixed ET is a characteristic of contractility in the heart. Systolic velocity of the atrioventricular annulus displacement is directly related to volume changes of the ventricle. Both ET and systolic velocity may be measured in a single heartbeat. In 29 neonatal pigs, systolic velocity and ET were measured with tissue Doppler techniques in the mitral valve annulus, the tricuspid valve annulus, and the septum. All ejection time corrected velocities (S((ET)), mean ± SEM, cm/s) decreased significantly during hypoxia (S(mva(ET)) 15.5 ± 0.2 to 13.2 ± 0.3 (p < 0.001), S(septal(ET)) 9.9 ± 0.1 to 7.8 ± 0.2 (p < 0.001), S(tva(ET)) 12.1 ± 0.2 to 9.8 ± 0.3 (p < 0.001)). The magnitude of change from baseline to hypoxia was greater for ejection time corrected systolic velocities than for RR-interval corrected velocities (mean ± SEM, cm/s); ΔS(mva(ET)) 2.3 ± 2.0 vs. ΔS(mva(RR)) 1.6 ± 1.1 (p = 0.02), ΔS(septal(ET)) 2.1 ± 1.0 vs. ΔS(septal(RR)) 1.6 ± 1.0 (p < 0.01), ΔS(tva(ET)) 2.3 ± 1.1 vs. ΔS(tva(RR)) 1.8 ± 1.3 (p = 0.04). The receiver operator characteristic (ROC) showed superior performance of S((ET)) compared with uncorrected velocities. The decrease in S((ET)) during hypoxia was not influenced by important hemodynamic determinants. ET-corrected systolic velocity improves accuracy and decreases variability in the evaluation of systolic longitudinal function and contractility during global hypoxia in neonatal pigs compared with systolic velocity alone. It is robust toward hemodynamic changes. This novel method has the potential of becoming a useful tool in clinical practice.

Early protective effect of hypothermia in newborn pigs after hyperoxic, but not after normoxic, reoxygenation.

Abstract Mild hypothermia can attenuate the development of brain damage after asphyxia. Supplemental oxygen during resuscitation increases generation of reactive oxygen species, compared to room air. It is unknown if supplemental oxygen affects hypothermic neuroprotection. We studied the early effects of hyperoxic reoxygenation and subsequent hypothermia on tissue oxygenation, microcirculation, inflammation and brain damage after global hypoxia. Anesthetized newborn pigs were randomized to control (n=6), or severe global hypoxia (n=46). Three pigs died during hypoxia or reoxygenation. After 20-min reoxygenation with room air (n=22) or 100% oxygen (n=21), pigs were randomized to normothermia (deep rectal temperature 39 degrees C, n=22) or total body cooling (35 degrees C, n=21) for 6.5 h before the experiment was terminated. We demonstrated a differential effect of post-hypoxic hypothermia between animals reoxygenated with 100% oxygen and with room air, with reduced damage only in hypothermic animals reoxygenated with 100% oxygen (P=0.001). Hyperoxic reoxygenation resulted in a significant overshoot in striatal oxygen tension, without affecting microcirculation. Inflammatory response after the insult did not differ between groups. The results indicate an early protective effect of hypothermia which may vary with oxygen level used during reoxygenation.

Resuscitation of hypoxic newborn piglets with supplementary oxygen induces dose-dependent increase in matrix metalloproteinase-activity and down-regulates vital genes.

The optimal oxygen concentration for newborn resuscitation is still discussed. Oxygen administration during reoxygenation may induce short- and long-term pathologic changes via oxidative stress and has been associated to later childhood cancer. The aim was to study changes in oxidative stress-associated markers in liver and lung tissue of newborn pigs after acute hypoxia followed by reoxygenation for 30 min with 21, 40, or 100% oxygen compared with room air or to ventilation with 100% oxygen without preceding hypoxia. Nine hours after resuscitation, we found a dose-dependent increase in the matrix metalloproteinase gelatinase activity in liver tissue related to percentage oxygen supply by resuscitation (100% versus 21%; p = 0.002) pointing at more extensive tissue damage. Receiving 100% oxygen for 30 min without preceding hypoxia decreased the expression of VEGFR2 and TGFBR3 mRNA in liver tissue, but not in lung tissue. MMP-, VEGF-, and TGFbeta-superfamily are vital for the development, growth, and functional integrity of most tissues and our data rise concern about both short- and long-term consequences of even a brief hyperoxic exposure.

Nicotine in a small-to-moderate dose does not cause a significant increase in plasma catecholamine levels in newborn piglets.

BACKGROUND: Nicotine has a wide range of effects. Several studies are being undertaken investigating the positive effects on inflammation and apoptosis. Recently, nicotine has been investigated in a piglet model of perinatal asphyxia, where the question has been raised whether nicotine's effect on the sympathetic nervous system can explain some of the positive effects. OBJECTIVES: We hypothesized that nicotine in small-to-moderate doses would not cause a significant increase in plasma catecholamine levels, whereas a higher dose would give a significant effect, confirming the believed dose-dependent matter in which nicotine exerts its effect on the sympathetic nervous system. METHODS: Seventeen anesthetized newborn piglets were randomized to one of three doses of nicotine (130, 260 or 1,000 microg/kg/h) that was given intravenously for 1 h. Blood samples for catecholamine analyzes were drawn at baseline and at the end of the infusion. Catecholamines were determined using HPLC. RESULTS: No significant increase in catecholamines was detected in the animals treated with the small or moderate nicotine doses, whereas the higher dose gave a significant increase in adrenaline (p = 0.019). CONCLUSION: Nicotine in small-to-moderate doses does not cause significant increase in plasma catecholamines, thus indicating that the positive effects of nicotine in studies using these doses most likely cannot be explained by the systemic release of catecholamines.

Resuscitation with 21 or 100% oxygen in hypoxic nicotine-pretreated newborn piglets: possible neuroprotective effects of nicotine.

BACKGROUND: Perinatal asphyxia is a major concern in perinatal medicine. Resuscitation and ways to prevent and minimize adverse outcomes after perinatal asphyxia are subject to extensive research. OBJECTIVES: In this study we hypothesized that, prior to hypoxia, intravenously administered nicotine might have an effect on how newborn piglets tolerate hypoxia, with regard to the time and degree of damage inflicted, due to its suggested neuroprotective abilities, and further that resuscitation with 21 compared with 100% oxygen in nicotine-pretreated animals would cause less cerebral damage. METHODS: Thirty anesthetized newborn piglets were randomized to either hypoxia or control groups, and pretreatment with either saline or nicotine. In addition, the nicotine/hypoxia group was randomized to resuscitation with either 21 or 100% oxygen for 15 min following hypoxia. RESULTS: We found significantly more necrosis in the striatum and cortex combined (p = 0.036), and in the striatum alone (p = 0.026), in the animals pretreated with nicotine and resuscitated with 100% when compared to 21% oxygen. There was no significant difference in the cerebellum. We also found significantly increased tolerance to hypoxia as measured by the time interval that the animals endured hypoxia: 103.8 +/- 28.2 min in the nicotine-pretreated animals vs. 66.5 +/- 19.5 min in the saline-pretreated animals (p = 0.035). CONCLUSION: Nicotine enhances newborn piglets' ability to endure hypoxia, and resuscitation with 21% oxygen inflicts less necrosis than 100% oxygen. The potential neuroprotective effects of nicotine in the newborn brain should be further investigated.

Magnetic resonance imaging of the Harderian gland in piglets.

The main purpose of the present study was to investigate the value and effectiveness of functional and morphological magnetic resonance imaging (MRI), in order to assess the extent of brain injury in a hypoxic-ischaemic piglet model, and further to validate that the ischaemic injury was successfully induced. In this way, we also characterized the Harderian gland. MRI was performed at 1.5 T in anaesthetized piglets (n = 10, 12-36 h of age). Magnetic resonance perfusion and diffusion imaging were performed at different time points, before, during and after the induction of hypoxia-ischaemia. The effects following bilateral clamping of the carotid arteries were also assessed by contrast-enhanced magnetic resonance angiography. Morphological assessment included T1- and T2-weighted imaging, and fat-suppressed T1-weighted imaging before and after contrast medium enhancement. Morphological MRI revealed a prominent, well-defined structure located at the eyeball. Magnetic resonance angiography reconstructed with volume rendering showed this structure to be partially enclosed by large venous sinuses. At dissection, when compared with the magnetic resonance images, the deep gland of the third eyelid, the Harderian gland, corresponded to this structure both in topography and in size. By contrast, the lacrimal gland proper presented as a small, soft and pale structure that was difficult to distinguish from the surrounding connective tissue. At histological examination, the Harderian gland consisted mainly of compact areas of tubuloacinar glands with abundant eosinophilic granules. The present MRI demonstration of the Harderian gland was an accidental finding during an investigation to assess the extent of brain injury in a hypoxic-ischaemic piglet model. The combination of MRI and histology made it possible to detect and describe the Harderian gland in pig. It has generally been studied in rodents and lower vertebrates and is reported to possess various endocrine and exocrine functions.

Fetal brain injury in experimental intrauterine asphyxia and inflammation in Göttingen minipigs.

OBJECTIVE: To examine fetal brain injury in the Göttingen minipig following intrauterine asphyxia and infection/inflammation induced at 3/4 of gestational length. METHODS: We performed laparotomy after anesthesia in six pregnant sows. We randomized 29 fetuses to one of four groups: pretreatment with saline or endotoxin followed by 30 min of umbilical cord occlusion or no occlusion. After 48 h we performed a re-laparotomy and examined the fetal brains. RESULTS: After total asphyxia, brain stem injury was present in the group pretreated with saline (P < 0.01 vs. controls) and with endotoxin (P < 0.005 vs. controls). Microglia activation was more marked in the brain stem (P < 0.05) and posterior white matter (P < 0.05) in the asphyxia group than in controls. Two of five fetuses in the asphyxia group had white matter injury, while no white matter lesions were found in the asphyxia/inflammation or endotoxin only groups. CONCLUSIONS: In this Göttingen minipig model, a species closer to humans than animals commonly used in experimental studies of perinatal brain injuries, intrauterine asphyxia following pretreatment with saline caused brain stem and white matter injury. This model can be further developed to study the impact of other intrauterine exposures on brain injury.

Effect of interleukin-10 on newborn piglet brain following hypoxia-ischemia and endotoxin-induced inflammation.

OBJECTIVE: Previous animal studies indicated that interleukin (IL)-10 attenuates the inflammatory response to a challenge by inflammation and hypoxia-ischemia, but the effect of IL-10 administration after onset of inflammation has not been studied. We wanted to assess (1) whether IL-10 had a beneficial effect on brain metabolism and microcirculation in newborn piglets after an inflammatory, hypoxic and ischemic challenge, and (2) whether IL-10 had any harmful effects per se. METHODS: Anesthetized piglets were randomized to control (n = 8), IL-10 (n = 10), endotoxin (ETX) (n = 10), or ETX and IL-10 (ETX/IL-10) (n = 10) groups. IL-10 was administered after pretreatment with saline in the IL-10 group or ETX in the ETX/IL-10 group. Then, cerebral hypoxia and ischemia was induced by bilateral clamping of the common carotid arteries and ventilation with 8% O(2) for 30 min, followed by 4 h of reoxygenation and reperfusion. Extracellular levels of lactate, pyruvate, and glycerol were measured with microdialysis in periventricular white matter and parasagittal subcortical tissue, and tissue oxygenation and microcirculation were measured with Doppler technique. We compared the areas under the concentration-time and flow-time curves and maximum concentrations between (1) the ETX/IL-10 and ETX groups, and (2) the control and IL-10 groups. RESULTS: We found no differences between (1) the ETX/IL-10 and ETX groups, and also no differences between (2) the control and IL-10 groups. CONCLUSION: We could not show that the treatment with IL-10 after onset of inflammation had neuroprotective effects in the newborn piglet brain. IL-10 did not attenuate metabolism in the absence of ETX-induced inflammation.

Resuscitation with 100% O2 increases cerebral injury in hypoxemic piglets.

Perinatal asphyxia is a major cause of immediate and postponed brain injury in the newborn. We hypothesized that resuscitation with 100% O2 compared with ambient air is detrimental to the cerebral tissue. We assessed cerebral injury in newborn piglets that underwent global hypoxia and subsequent resuscitation with 21 or 100% O2 by extracellular glycerol, matrix metalloproteinase (MMP) expression levels, and oxidative stress. Extracellular glycerol was sampled by cerebral microdialysis. MMP levels were analyzed in cerebral tissue by gelatin zymography, broad matrix degrading capacity, and real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity assay. Extracellular glycerol increased 50% after resuscitation with 100% O2 compared with 21% O2. Total MMP activity was doubled in resuscitated animals at endpoint compared with baseline (p=0.018), and the MMP-2 activity was significantly increased in piglets that were resuscitated with 21% O(2) (p=0.003) and 100% O2 (p=0.001) compared with baseline. MMP-2 mRNA level was 100% increased in piglets that were resuscitated with 100% O2 as compared with 21% O2 (p < 0.05). Oxygen radical absorbance capacity values in piglets that were resuscitated with 100% O2 were considerably reduced compared with both baseline (p=0.001) and piglets that were resuscitated with 21% O2 (p=0.001). In conclusion, our data show increased MMP-2 activity at both gene and protein levels, accompanied with cerebral leakage of glycerol, presumably triggered by augmented oxidative stress. Our findings suggest that resuscitation of asphyxiated piglets with 100% O2 is detrimental to the piglet brain compared with resuscitation with 21% O2.

Morphological and hemodynamic magnetic resonance assessment of early neonatal brain injury in a piglet model.

PURPOSE: To investigate the utility of functional and morphological magnetic resonance imaging (MRI) to assess the extent of brain injury in a hypoxia-ischemia (HI) piglet model and further to validate that the desired ischemic injury was successfully induced. MATERIALS AND METHODS: MRI was performed at 1.5 T in anesthetized piglets (N = 10, age = 12-36 hours). Relative cerebral blood flow (rCBF), time-to-peak (TTP) contrast, and apparent diffusion coefficient (ADC) were estimated at different time points pre-, during, and post-HI. The effect following bilateral clamping of the carotid arteries was assessed by contrast-enhanced MR angiography (MRA) and phase contrast MR angiography (PCA) (N = 4). RESULTS: A linear correlation was observed between relative cerebral perfusion reduction and cerebral ADC during HI (r(2) = 0.85, P < 0.05). There was no correlation between rCBF reduction during 30 minutes of HI and cerebral ADC after 30 or 150 minutes of reperfusion/reoxygenation (RR). CONCLUSION: The combination of morphological and functional (perfusion and diffusion) MRI enabled consistent assessment of both the presence and absence of complete occlusion as well as the functional significance of the occlusion.

Interleukin-10 reverses acute detrimental effects of endotoxin-induced inflammation on perinatal cerebral hypoxia-ischemia.

UNLABELLED: Perinatal brain injuries and the subsequent development of cerebral palsy are closely associated with intrauterine infections and inflammatory response. Antibiotics have proven futile in reducing perinatal brain injuries. We tested whether treatment with the anti-inflammatory cytokine IL-10 could have beneficial effects during a concomitant endotoxin and cerebral hypoxic-ischemic challenge. Thirty-three newborn piglets were randomized to pretreatment with: CONTROLS: placebo, Endotoxin: 2 kU/kg bolus and infusion of 1 kU/kg per h of endotoxin, or Endotoxin+IL-10: endotoxin in addition to 50 microg/kg of porcine recombinant IL-10. We induced cerebral hypoxia-ischemia by bilateral clamping of the common carotid arteries and ventilation with 8% oxygen for 20 min followed by 3 h of reoxygenation/reperfusion. Extracellular lactate, pyruvate, glycerol and glutamate, microcirculation and tissue oxygenation were monitored in the striatum by microdialysis, laser Doppler flow and oxygen tension probe, respectively. During and/or after cerebral hypoxia-ischemia, Endotoxin caused marked deterioration of the cerebral metabolic situation with higher lactate/pyruvate ratio (P=0.003), compared to CONTROLS and Endotoxin+IL-10. This was caused mainly by very low levels of pyruvate (P=0.001). During the following reoxygenation, Endotoxin compromised cerebral microcirculation (P=0.038) and tissue oxygenation (P=0.012) compared to CONTROLS and Endotoxin+IL-10. After a period of remission, a secondary energy failure and a new rise in the lactate/pyruvate ratio was seen in Endotoxin (P=0.002), but not in CONTROLS or Endotoxin+IL-10. At the end of observation, only the Endotoxin+IL-10 group had regained their baseline values in all variables. Thus IL-10 counteracts acute effects of endotoxin on cerebral metabolism, microcirculation and oxygen tension during hypoxia-ischemia in the perinatal brain.