Multiparametric Monitoring of Early Pathophysiological Changes in a Porcine Model of Sequential Focal and Global Cerebral Ischemia

Abstract

Objective: Large animal models of cerebral ischemia have the potential to increase the translational value of stroke research. This study aims to measure early changes of brain tissue oxygen pressure (ptiO₂) and cerebral blood flow (CBF) to characterize a porcine model of sequential middle cerebral artery occlusion (MCAO) and common carotid artery occlusion (CCAO).

Methods: Eight juvenile German Landrace pigs received unilateral MCAO via a frontotemporal approach under continuous intraparenchymal multiparametric monitoring. Insufficient reduction (i.e., <50% in both ptiO₂ and CBF) was followed by additional bilateral CCAO. Neurodegenerative changes were detected by Fluoro-Jade B (FJB) staining.

Results: Only 1 of 8 animals demonstrated a decrease of >50% in both ptiO₂ and CBF after MCAO. Additional CCAO in 7 pigs led to a significant reduction of both ipsilateral and contralateral ptiO₂ (P < 0.01) but not of CBF. There was no difference in ptiO₂ and FJB positive area between hemispheres in this group. Measurement of ptiO₂ correlated negatively with the FJB positive area (P < 0.05).

Conclusions: Intraparenchymal multiparametric measurements of acute changes in ptiO₂ and CBF were variable after MCAO. Bilateral CCAO led to a consistent decrease in ptiO₂ and correlated with early degenerative histologic changes, but CBF did not. Real-time procedural ptiO₂ monitoring could provide useful guidance in large animal ischemia models. Feasibility in the context of global cerebral hypoperfusion is demonstrated.

Keywords: Cerebrovascular circulation; Infarction; Middle cerebral artery; Oxygen; Perfusion; Stroke; Swine.