Pial Collateral Reactivity During Hypertension and Aging

Abstract

Background and Purpose We investigated vasoactive properties of leptomeningeal arterioles (LMAs) under normotensive conditions and during hypertension and aging that are known to have poor collateral flow and little salvageable tissue. Methods LMAs, identified as distal anastomotic arterioles connecting middle and anterior cerebral arteries, were studied isolated and pressurized from young (18 weeks) or aged (48 weeks) normotensive Wistar Kyoto (WKY18, n=14; WKY48, n=6) and spontaneously hypertensive (SHR18, n=16; SHR48, n=6) rats. Myogenic tone and vasoactive responses to pressure as well as endothelial function and ion channel activity were measured. Results LMAs from WKY18 had little myogenic tone at 40 mm Hg (8±3%) that increased in aged WKY48 (30±6%). However, LMAs from both WKY groups dilated to increased pressure and demonstrated little myogenic reactivity, a response that would be conducive to collateral flow. In contrast, LMAs from both SHR18 and SHR48 displayed considerable myogenic tone (56±8% and 43±7%; p<0.01 vs. WKY) and constricted to increased pressure. LMAs from both WKY and SHR groups had similar basal endothelial NO and IK channel activity that opposed tone. However, dilation to sodium nitroprusside, diltiazem and 15 mmol/L KCl was impaired in LMAs from SHR18. Conclusion This study shows for the first time that LMAs from young and aged SHR are vasoconstricted and have impaired vasodilatory responses that may contribute to greater perfusion deficit and little penumbral tissue. These results also suggest that therapeutic opening of pial collaterals is possible during MCAO to create penumbral tissue and prevent infarct expansion.

Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies

“…We are not aware of previous studies of P t O 2 in SHRs during MCAo. This probably reflects this strain’s poor leptomeningeal collaterals and impaired cerebrovascular autoregulation, resulting from increased vessel stiffness, thicker wall and reduced lumen [ 39 , 41 – 45 ].…”

“…To test this hypothesis, we assessed not only brain tracer retention at the standard 2-3hrs post-administration time, but also FMISO kinetic rate constants, specifically the irreversible trapping constant thought to reflect tissue hypoxia, by dynamically acquiring FMISO brain data since administration time and applying our previously reported quantitative kinetic model [ 32 ]. In addition, to assess the effects of hyperoxia on FMISO uptake in distinct tissue situations, we used both Wistar rats and their spontaneously hypertensive counterparts (SHRs), whose tissue vulnerability to focal cerebral ischemia, namely rate of demise of the severely hypoxic but viable tissue (i.e., the penumbra) [ 33 – 35 ] and final infarct volume [ 33 , 36 – 40 ], widely differ as a result of underlying differences in functionality and structure of the pial vascular tree [ 39 , 41 – 45 ], in turn mimicking clinical heterogeneity. In parallel to testing the effects of hyperoxia on FMISO uptake, and to inform the findings thereof, we also assessed its effects on tissue oxygen tension in both ischemic and non-ischemic cortex in a different group of animals.…”

Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

“…A recent study found that myogenic tone and reactivity are quite different in collateral versus non-collateral arterioles. 174 During hypertension for example, collaterals have increased tone and impaired vasodilation which may result in lower levels of collateral-dependent blood flow, contributing to greater infarct size in response to ischemia. 174 …”

Clinical and Imaging Determinants of Collateral Status in Patients With Acute Ischemic Stroke in MR CLEAN Trial and Registry

“…high systolic blood pressure, location of the occlusion, presence of extracranial internal carotid artery (ICA) stenosis and poor hydration status are related to worse collateral status. [13][14][15][16][17][18] Further research on potential determinants for poor collateral status could improve our understanding of the collateral system. Possibly, this might help to find ways to improve collateral status during acute ischemic stroke and thus increase chances of a better clinical outcome.…”