Objective: We used a piglet model with different mechanisms of bypass-related brain injury to study (1) neuronal vulnerability, (2) relation between cerebral microcirculation and regional neuronal damage and (3) accuracy of intra-operative monitoring in predicting damage.
Methods: Eighty piglets assigned to bypass groups with different ischemic insults: ultra-low flow at 25oC (control), circulatory arrest at 25oC (hypo-oxygen supply stress), and ultra-low flow at 34oC (high-oxygen consumption stress). Near-infrared spectroscopy (NIRS) was used to measure tissue-oxygenation index (TOI) and oxyhemoglobin (HbO2) nadir time. Functional capillary density (FCD) and leukocyte activation in cortex was assessed by intravital micrsocopy. Histological neuronal damage scores was the primary outcome. Secondary measures included functional outcome.
Results: Significant neuronal damage was observed in cortex, hippocampus, caudate nucleus, and Purkinje cells. Histological score correlated with impaired FCD and leukocyte activation. TOI and HbO2 nadir time predicted degree of injury. Histological damage in cortex and Purkinje cells was not different between bypass states, while the caudate nucleus was vulnerable to hypoxic supply stress and the hippocampus was vulnerable to high-oxygen consumption stress. Neurological recovery was lower under hypo-oxygen supply stress than high-consumption stress. Neurological recovery was significantly correlated with neuronal damage in cortex, Purkinje cells, and caudate nucleus but did not correlate with damage in the hippocampus.
Conclusion: Vulnerability of neurons depends on the mechanism of the bypass-related ischemic insult. NIRS can predict injury. Injury to hippocampal neurons which are critical to memory may not be apparent in assessing acute neurological recovery but is important for long-term brain function.