Meconium aspiration induces neuronal injury in piglets
Corresponding Author
Minna Aaltonen
Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), University Hospital of Turku, Turku, Finland
Department of Paediatrics, University Hospital of Turku, Turku, Finland
M. Aaltonen, Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), Kiinamyllynkatu 10, FIN-20520 Turku, Finland. Tel: +358 2 3337558. Fax: +358 2 2331126. E-mail: [email protected]Search for more papers by this authorHanna Soukka
Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), University Hospital of Turku, Turku, Finland
Department of Paediatrics, University Hospital of Turku, Turku, Finland
Search for more papers by this authorLauri Halkola
Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), University Hospital of Turku, Turku, Finland
Search for more papers by this authorHannu Kalimo
Department of Neuropathology, University of Turku, Turku, Finland
Search for more papers by this authorIrma E Holopainen
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland
Search for more papers by this authorPekka O Kääpä
Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), University Hospital of Turku, Turku, Finland
Department of Paediatrics, University Hospital of Turku, Turku, Finland
Search for more papers by this authorCorresponding Author
Minna Aaltonen
Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), University Hospital of Turku, Turku, Finland
Department of Paediatrics, University Hospital of Turku, Turku, Finland
M. Aaltonen, Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), Kiinamyllynkatu 10, FIN-20520 Turku, Finland. Tel: +358 2 3337558. Fax: +358 2 2331126. E-mail: [email protected]Search for more papers by this authorHanna Soukka
Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), University Hospital of Turku, Turku, Finland
Department of Paediatrics, University Hospital of Turku, Turku, Finland
Search for more papers by this authorLauri Halkola
Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), University Hospital of Turku, Turku, Finland
Search for more papers by this authorHannu Kalimo
Department of Neuropathology, University of Turku, Turku, Finland
Search for more papers by this authorIrma E Holopainen
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland
Search for more papers by this authorPekka O Kääpä
Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), University Hospital of Turku, Turku, Finland
Department of Paediatrics, University Hospital of Turku, Turku, Finland
Search for more papers by this authorAbstract
Aim: Meconium aspiration-induced hypertensive lung injury, especially when connected with perinatal asphyxia, has been associated with brain damage. We aimed to determine the neuronal injury induced by pulmonary meconium contamination alone and with concurrent asphyxia. Methods: 36 anaesthetized and ventilated newborn piglets were haemodynamically monitored for 6 h. Seven piglets without concurrent asphyxia and seven piglets with asphyxia were instilled with a bolus of human meconium intratracheally. Seven piglets had only asphyxia and 15 piglets served as controls. The brains were studied histologically. Results: Meconium aspiration did not change systemic haemodynamics acutely, while its combination with asphyxia diminished the abrupt postasphyxic systemic hypertensive peak and resulted in a transient increase in carotid artery flow, not seen after isolated asphyxia. Systemic pressure declined after 4 h in all insulted groups, but only isolated asphyxia was associated with a sustained decrease in carotid artery flow. Arterial oxygenation remained normal, except during the acute insults. Brain examination after meconium instillation indicated neuronal injury, especially in the CA3 region of the hippocampus. Asphyxia resulted in neuronal injury in the cortical, cerebellar and hippocampal hilus regions.
Conclusion: Severe meconium aspiration itself may result in hippocampal neuronal injury.
References
- [1] Cleary GMWiswell TE Meconium-stained amniotic fluid and the meconium aspiration syndrome. An update Pediatr Clin North Am 1998 45 511–29
- [2] Davey AMBecker JDDavis JM Meconium aspiration syndrome: physiological and inflammatory changes in a newborn piglet model Pediatr Pulmonol 1993 16 101–8
- [3] Sell EJGaines JAGluckman CWilliams E Persistent fetal circulation. Neurodevelopmental outcome Am J Dis Child 1985 139 25–8
- [4]
Wiswell TE Meconium staining and the meconium aspiration syndrome Fetal and neonatal brain injury. Mechanisms, management and the risks of practice 3rd ed D Stevenson WE Benitz P Sunshine
Cambridge University Press
Cambridge
UK
2003 612–35
10.1017/CBO9780511544774.033 Google Scholar
- [5] Naeye RL Can meconium in the amniotic fluid injure the fetal brain Obstet Gynecol 1995 86 720–4
- [6] Montgomery LDBelfort MA Can meconium in the amniotic fluid injure the fetal brain Obstet Gynecol 1996 87 320
- [7] Thibeault DWHall FKSheehan MBHall RT Postasphyxial lung disease in newborn infants with severe perinatal acidosis Am J Obstet Gynecol 1984 150 393–9
- [8] Perlman JMTack EDMartin TShackelford GAmon E Acute systemic organ injury in term infants after asphyxia Am J Dis Child 1989 143 617–20
- [9] Carter BSHaverkamp ADMerenstein GB The definition of acute perinatal asphyxia Clin Perinatol 1993 20 287–304
- [10] Klesh KWMurphy TFScher MSBuchanan DEMaxwell EPGuthrie RD Cerebral infarction in persistent pulmonary hypertension of the newborn Am J Dis Child 1987 141 852–7
- [11] Aaltonen MSoukka HHalkola LJalonen JHolopainen IEKero P Asphyxia aggravates systemic hypotension but not pulmonary hypertension in piglets with meconium aspiration Pediatr Res 2003 53 473–8
- [12] Deshpande JBergstedt KLinden TKalimo HWieloch T Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia: evidence against programmed cell death Exp Brain Res 1992 88 91–105
- [13] Nakajima WIshida ALange MSGabrielson KLWilson MAMartin LJ Apoptosis has a prolonged role in the neurodegeneration after hypoxic ischemia in the newborn rat J Neurosci 2000 20 7994–8004
- [14] Holopainen RAho HLaine JPeuravuori HSoukka HKaapa P Human meconium has high phospholipase A2 activity and induces cellular injury and apoptosis in piglet lungs Pediatr Res 1999 46 626–32
- [15] Martin LJBrambrink AMPrice ACKaiser AAgnew DMIchord RN Neuronal death in newborn striatum after hypoxia-ischemia is necrosis and evolves with oxidative stress Neurobiol Dis 2000 7 169–91
- [16] Northington FJFerriero DMGraham EMTraystman RJMartin LJ Early Neurodegeneration after hypoxia-ischemia in neonatal rat is necrosis while delayed neuronal death is apoptosis Neurobiol Dis 2001 8 207–19
- [17] Haas KZSperber EFOpanashuk LAStanton PKMoshe SL Resistance of immature hippocampus to morphologic and physiologic alterations following status epilepticus or kindling Hippocampus 2001 11 615–25
- [18] Humphrey WMDong HCsernansky CACsernansky JG Immediate and delayed hippocampal neuronal loss induced by kainic acid during early postnatal development in the rat Brain Res Dev Brain Res 2002 137 1–12
- [19] Marks JDFriedman JEHaddad GG Vulnerability of CA1 neurons to glutamate is developmentally regulated Brain Res Dev Brain Res 1996 97 194–206
- [20] Holmes GLBen-Ari Y The neurobiology and consequences of epilepsy in the developing brain Pediatr Res 2001 49 320–5
- [21] Roohey TRaju TNMoustogiannis AN Animal models for the study of perinatal hypoxic-ischemic encephalopathy: a critical analysis Early Hum Dev 1997 47 115–46
- [22] Haworth SGHislop AA Adaptation of the pulmonary circulation to extra-uterine life in the pig and its relevance to the human infant Cardiovasc Res 1981 15 108–19
- [23] Sie LTvan der Knaap MSOosting Jde Vries LSLafeber HNValk J MR patterns of hypoxic-ischemic brain damage after prenatal, perinatal or postnatal asphyxia Neuropediatrics 2000 31 128–36
- [24] Walther FJSiassi BRamadan NAWu PY Cardiac output in newborn infants with transient myocardial dysfunction J Pediatr 1985 107 781–5
- [25] Hansen NBBrubakk AMBratlid DOh WStonestreet BS The effects of variations in PaCO2 on brain blood flow and cardiac output in the newborn piglet Pediatr Res 1984 18 1132–6
- [26] Kusuda SShishida NMiyagi NHirabayashi MKim TJ Cerebral blood flow during treatment for pulmonary hypertension Arch Dis Child Fetal Neonatal Ed 1999 80 F30–3
- [27] Ballot DERothberg ADDavies VASmith JKirsten G Does hypoxemia prevent brain damage in birth asphyxia Med Hypotheses 1993 41 344–7
- [28] Soukka HViinikka LKaapa P Involvement of thromboxane A2 and prostacyclin in the early pulmonary hypertension after porcine meconium aspiration Pediatr Res 1998 44 838–42
- [29] Soukka HRAhotupa MRuutu MKaapa PO Meconium stimulates neutrophil oxidative burst Am J Perinatol 2002 19 279–84
- [30] Beligere NRao R Neurodevelopmental outcome of infants with meconium aspiration syndrome (MAS) Pediatr Res 2002 51 293A