Decreased brainstem function following cardiac arrest and resuscitation in aged rat

There is a high incidence of cardiac arrest and poorer post-resuscitation outcome in the elderly population. Cardiac arrest and resuscitation results in ischemia/reperfusion injury associated with oxidative stress, leading to post-resuscitation mortality and delayed selective neuronal cell loss. In this study we investigated recovery following cardiac arrest and resuscitation in the aged rat brain. Male Fischer 344 rats (6, 12 and 24 months old) underwent 7 minute cardiac arrest before resuscitation. Overall survival and hippocampal neuronal counts were determined at 4 days of recovery. Brainstem function was assessed by hypoxic ventilatory response (HVR). Mitochondria of brainstem, cortex and hippocampus were isolated and assessed for respiratory function. Effect of an antioxidant, alpha-phenyl-tert-butyl-nitrone (PBN) was used as a treatment strategy against oxidative stress in the 6 and 24-month old rats. The time course of mitochondrial function was established using 3-month old Wistar rats with 12-minute cardiac arrest. In the 24-month old rats, overall survival rate, hippocampal CA1 neuronal counts, HVR, and brain mitochondrial respiratory control ratio were significantly reduced following cardiac arrest and resuscitation compared to the younger rats, and PBN treatment improved outcome. The data suggest that (i) there was increased susceptibility to ischemia/reperfusion in aged rat brain; (ii) HVR was decreased in the aged rats; (iii) brain mitochondrial respiratory function related to coupled oxidation was decreased following cardiac arrest and resuscitation in rats, more so in the aged; and (iv) treatment with an antioxidant, such as PBN, reduced the oxidative damage following cardiac arrest and resuscitation.