title: Cerebrovascular dysfunction following subfailure axial stretch.
abstract: Cerebral blood vessels are vital to maintaining the health of the brain. Traumatic brain injury (TBI) commonly results in autoregulatory dysfunction and associated failure of cerebral vessels to maintain homeostasis in the brain. While post-injury changes to brain biochemistry are known to contribute to this dysfunction, tissue deformation may also directly alter vascular smooth muscle cell (SMC) function. As a first step toward understanding stretch-induced dysfunction, this study investigates the effect of overstretch on the contractile behavior of SMCs in middle cerebral arteries (MCAs). We hypothesized that vessel function is altered above a threshold of stretch and strain rate. Twenty-four MCAs from Sprague Dawley rats were tested. Following development of basal SMC tone, vessels were subjected to increasing levels of isosmotic extracellular potassium (K+). Samples were then subjected to an axial overstretch of either 1.2*λIVor 1.3*λIVat strain rates of 0.2 or 20s-1. Following overstretch, SMC contractile behavior was measured again, both immediately and 60min after overstretch. Control vessels were subjected to the same protocol but without overstretch. SMC contractile behavior was characterized using both percent contraction (%C) relative to the fully dilated inner diameter and the K+dose required to evoke the half maximal contractile response (EC50). Control vessels exhibited increased sensitivity to K+in successive characterization tests, so all effects were quantified relative to the time-matched control response. Samples exhibited the typical biphasic response to extracellular K+, dilating and contracting in response to small and large K+concentrations, respectively. As hypothesized, axial overstretch altered SMC contractile behavior, as seen in a decrease in %C for sub-maximal contractile K+doses (p<0.05) and an increase in EC50 (p<0.01), but only for the test group stretched rapidly to 1.3*λIV. While the change in %C was only significantly different immediately after overstretch, the change to EC50 persisted for 60min. These results indicate that deformation can alter SMC contractile behavior and thus potentially play a role in cerebrovascular autoregulatory dysfunction independent of the pathological chemical environment in the brain post-TBI.
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT, USA; Laboratory of Head Injury and Vessel Biomechanics, Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, USA.
authors.forename: E David
authors.initials: ED
authors.lastname: Bell
authors.affiliation: Department of Internal Medicine, Division of Geriatrics, University of Utah, Salt Lake City, UT, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.affiliation: Department of Bioengineering, University of Utah, Salt Lake City, UT, USA; Laboratory of Head Injury and Vessel Biomechanics, Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, USA. Electronic address: ken.monson@utah.edu.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Monson
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000503:physiopathology*; D006706:Homeostasis; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Autoregulatory dysfunction; Damage; Rat cerebral blood vessels; Traumatic brain injury