Rate and extent of leakage of a magnetic resonance contrast agent tend to be lower under isoflurane anesthesia in comparison to halothane in a rat model of embolic stroke

Abstract

Cerebral blood flow (CBF) and blood–brain barrier (BBB) permeability by arterial spin labeling (ASL)- and dynamic contrast enhanced (DCE)-magnetic resonance imaging (MRI), respectively were repeatedly measured under either halothane (N  =  5) or isoflurane (N  =  5) anesthesia in a rat stroke model of embolic occlusion of middle cerebral artery (MCA). Cerebral blood flow measurements were made after MCA embolization, following intravenous recombinant tissue plasminogen activator (rtPA) treatment at 3 hours post-ictus and again at 48 hours. Blood–brain barrier opening was examined after rtPA infusion and again at 48 hours. Data were analyzed using paired t-tests and significance considered at P < 0·05. The extent and magnitude of CBF reduction due to stroke did not differ between the two groups. Blood-to-brain forward rate constant, K^trans, a measure of BBB permeability, for an MRI contrast agent gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), was elevated in the ipsilateral hemisphere in both cohorts. However, isoflurane-anesthetized rats exhibited a trend of lower K^trans values at 48 hours (P  =  0·06) indicating reduced BBB damage in the ipsilateral hemisphere. The area of BBB opening followed a similar trend with the isoflurane-anesthetized group exhibiting a smaller area of BBB damage acutely and at 48 hours compared to the halothane-anesthetized group.

Keywords:

• ASL-MRI
• Blood–brain barrier
• DCE-MRI
• Inhalational anesthetics
• K^trans
• Middle cerebral artery

Acknowledgements

The authors thank Jun Xu for technical assistance and Dr J. D. Fenstermacher for helpful suggestions. Research reported in this publication was supported by American Heart Association – Scientist Development Grant (0635403N). Recombinant tissue plasminogen activator was a kind gift from Genentech, Inc. (San Francisco, CA, USA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the American Heart Association.