Transient Aortic Occlusion Augments Collateral Blood Flow and Reduces Mortality During Severe Ischemia due to Proximal M
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SHORT COMMUNICATION
Transient Aortic Occlusion Augments Collateral Blood Flow and Reduces Mortality During Severe Ischemia due to Proximal Middle Cerebral Artery Occlusion Gomathi Ramakrishnan 1,2 & Bin Dong 1 & Kathryn G. Todd 1,2 & Ashfaq Shuaib 2,3 & Ian R. Winship 1,2
Received: 13 July 2015 / Revised: 13 December 2015 / Accepted: 14 December 2015 # The Author(s) 2015. This article is published with open access at Springerlink.com
Abstract Cerebral collateral circulation provides alternative vascular routes for blood to reach ischemic tissues during stroke. Collateral therapeutics attempt to augment flow through these collateral channels to reduce ischemia and brain damage during acute ischemic stroke. Transient aortic occlusion (TAO) has pre-clinical data suggesting that it can augment collateral blood flow and clinical data suggesting a benefit for patients with moderate cortical strokes. By diverting blood from the periphery towards the cerebral circulation, TAO has the potential to augment primary collateral flow at the circle of Willis and thereby improve outcome even during large, hemispheric strokes. Using proximal middle and anterior cerebral artery occlusion in rats, we demonstrate that TAO reduces mortality and improves collateral blood flow in severely ischemic animals. As such, TAO may be an effective therapy to reduce early mortality during severe ischemia associated with proximal occlusions.
Keywords Stroke . Collateral blood flow . Ischemia . Neuroprotection . Collateral therapeutics . Cerebral blood flow
* Ian R. Winship [email protected]
1
Neurochemical Research Unit, Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
2
Neuroscience and Mental Health Institute, University of Alberta, 12-127 Clinical Sciences Building, Edmonton, AB, Canada T6G 2R3
3
Division of Neurology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
Collateral circulation refers to pre-existing vascular redundancies that provide a route for blood to reach a target tissue when a primary channel is blocked [1–5]. Primary cerebral arterial collaterals refer to short arterial segments in the circle of Willis that allow blood flow between the territories of the internal carotid arteries and the vertebrobasilar system or between cerebral hemispheres in the event of proximal occlusion. The secondary cerebral collaterals include the pial (or leptomeningeal) collaterals, which are anastomotic connections located on the surface of the cortex that connect distal branches of the anterior, middle, and posterior cerebral arteries (ACA, MCA, PCA). These collateral channels permit blood flow from the territory of an unobstructed artery into the territory of an occluded artery (e.g., retrograde filling of the MCA territory via anastomoses with the ACA after middle cerebral artery occlusion (MCAo)) [2–4, 6]. Collateral extent is crucial, as in both animal models and human stroke patients the degree of collateral perfusion
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