Regional Dependence of Cerebral Reperfusion after Circulatory Arrest in Rats

Abstract

The severity of neurologic dysfunction after circulatory arrest depends on cerebral reperfusion during and after resuscitation. The objective of current study was to investigate the temporal and spatial patterns of the cerebral perfusion immediately after resuscitation. Precise control of circulatory arrest was achieved in rats by combination of asphyxia and transient blockage of cardiac-specific β-adrenergic receptors with esmolol, an ultra-short-acting β-blocker. Animals were randomized into 3 groups with resuscitation starting 0.5 (sham group, no asphyxia, n = 5), 4 (Group 2, n = 5), or 12 minutes (Group 3, n = 8) later by retrograde intraarterial infusion of donor blood along with a resuscitation mixture. Cerebral perfusion was measured by magnetic resonance imaging (MRI) using arterial spin labeling. The average perfusion before arrest was 163 ± 27 mL 100 g−1 min−1 under isoflurane anesthesia. Resuscitation led to transient perfusion increase, which started from thalamus and hypothalamus and later shifted to the cortex. Severe hypoperfusion to as low as 6% to 20% of the normal level developed in the first 10 to 20 minutes of reperfusion and lasted for at least 2 hours. On the fifth day after circulatory arrest, all animals showed a normal level of perfusion (159 ± 57 mL 100 g−1 min−1) and minimal neurologic deficit. Nevertheless, histologic examination revealed extensive changes in the CA1 region of the hippocampus consistent with global ischemia and reperfusion damage. The combination of an improved circulatory arrest model and noninvasive MRI cerebral perfusion measurements provides a powerful tool for investigations of circulatory arrest and resuscitation, allowing for evaluation of therapies aimed at modulating cerebral reperfusion.