[Show abstract][Hide abstract] ABSTRACT: To examine fetal brain injury in the Göttingen minipig following intrauterine asphyxia and infection/inflammation induced at 3/4 of gestational length.
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.
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.
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.
Journal of Perinatal Medicine 02/2006; 34(3):226-34. DOI:10.1515/JPM.2006.041 · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to assess whether inflammation increases vulnerability to hypoxia, and influences the effect of 100% O(2) and 21% O 2 reoxygenation on brain.
Newborn piglets (n = 31) were randomized to 4 interventional groups: pretreatment with saline or endotoxin. After hypoxia they were reoxygenated with 21% or 100% oxygen for 30 minutes, followed by 21% oxygen for all groups. To assess brain injury we measured extracellular brain tissue glucose, glycerol, and lactate/pyruvate by microdialysis, brain tissue oxygen tension, and laser Doppler flow.
Administration of endotoxin reduced the time to reach base excess (BE) -20 mmol/L by median 32 minutes compared with saline ( P < .05). We found no differences in changes in biochemical markers, brain tissue microcirculation, or oxygen tension between piglets in the 4 groups.
Endotoxin and hypoxia acted synergistically in inducing metabolic acidosis. In the presence of experimental inflammation, 21% oxygen seems as effective as 100% O(2) in reoxygenating piglets.
American Journal of Obstetrics and Gynecology 04/2005; 192(4):1172-8. DOI:10.1016/j.ajog.2004.11.058 · 4.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Biology of the Neonate 02/2005; 87(3):207-16. DOI:10.1159/000083131 · 1.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Occasionally, an obstetrician can experience conflicts between the mother and her fetus. In a situation where the life of the fetus is in danger, religious, cultural, or other convictions may cause the mother to refuse the physician's recommendations for delivery. When there is a medical indication to perform cesarean section, but the mother refuses, has the obstetrician then a right to perform a cesarean section to save the fetus from possible death or serious injury? In 1987, The Norwegian Directorate of Health made a statement on cesarean section without consent, but later, new legislation on patient rights has been introduced. In Norway, no scientific medical articles have been published on this topic, and no cases have yet been brought to court. Cases of court-ordered cesarean section have been reported from the UK and the USA. In this report, we discuss some of the ethical, moral, and legal aspects of forced cesarean sections.
[Show abstract][Hide abstract] ABSTRACT: Objective: To assess if endotoxin increases vulnerability to hypoxia and if resuscitation with 100% O2 increases brain damage in the presence of inflammation.Method: After anaesthesia and surgery, newborn piglets (n=31) were randomized to four interventional groups. Two groups received pretreatment with saline for 60 min followed by hypoxia and resuscitation with 21% (Group I, n=8) or 100% oxygen (Group II, n=8). The other two groups received pretreatment with endotoxin for 60 min followed by hypoxia and resuscitation with 21% (Group III, n=7) or 100% oxygen (Group IV, n=8). Hypoxia was administered until base excess (BE) reached –20 mmol/L. Reoxygen with either 21% oxygen or 100% oxygen was administered for the first 30 minutes, followed by 21% oxygen for 150 min for all groups. During the experiment, we measured extracellular brain tissue glucose, glycerol, and lactate/pyruvate by microdialysis, brain tissue oxygen tension and laser doppler flow.Results: Administration of endotoxin caused a reduction in the time to reach BE –20 by median 31.5 minutes compared with saline (p<0.05). We found no differences in biochemical markers, brain tissue microcirculation or brain tissue oxygen tension between piglets pretreated with saline or endotoxin and resuscitated with room air or 100% oxygen in the four groupsConclusion: Endotoxin and hypoxia acted synergistically in inducing arterial acidosis. In the presence of experimental inflammation, 21% seems as safe as 100% O2 in reoxygenating newborn piglets.
Pediatric Research 09/2004; 56(3). DOI:10.1203/00006450-200409000-00189 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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).
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.
Journal of Magnetic Resonance Imaging 07/2004; 20(1):8-15. DOI:10.1002/jmri.20084 · 3.21 Impact Factor