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Decreased brainstem response in aged rat following transit global ischemia
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.90.3
Subject(s) - brainstem , resuscitation , lipid peroxidation , medicine , hypoxia (environmental) , anesthesia , ischemia , endocrinology , oxidative stress , chemistry , oxygen , organic chemistry
The age‐related changes in rat brainstem following transient global ischemia were investigated. In our model of cardiac arrest and resuscitation, the 4‐day survival rate is lower in old (24 months, 40%) than in young (6 months, 70%) rats. Decreased brainstem response in the aged may be a major factor for the higher post‐resuscitation mortality. Brainstem function was assessed by measuring hypoxic ventilatory response (HVR; minute volume ratio, hypoxia vs. normoxia) in 6‐ and 24‐month old Fischer 344 rats after cardiac arrest and resuscitation. Brainstem mitochondria were isolated and assayed for respiratory function. Levels of 4‐hydroxy‐2‐nonenal (HNE) modified proteins were assayed for lipid peroxidation. The effect of an antioxidant, alpha ‐phenyl‐ tert ‐butyl‐nitrone (PBN) was also tested. Results indicated a significant decrease (27%) in HVR in the old compared to the young rats. At 1h recovery, a significantly lower respiratory control ratio (RCR; State 3/State 4) was observed in the aged. PBN treatment improved the decreased HVR and RCR and also reduced the elevated HNE production. These data suggest that increased mortality in the aged is associated with brainstem dysfunction. The antioxidant treatment results in improved brainstem mitochondrial function, decreased mitochondrial lipid peroxidation and increased survival rates in the older rats following cardiac arrest and resuscitation.