Cerebrovascular Dysfunction Following Subfailure Axial Stretch

Details

• Personal Author:
  Bell DE ; Donato AJ ; Monson KL
• Description:
  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*lambdaIV or 1.3*lambdaIV at strain rates of 0.2 or 20 s-1. Following overstretch, SMC contractile behavior was measured again, both immediately and 60 min 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*lambdaIV. While the change in %C was only significantly different immediately after overstretch, the change to EC50 persisted for 60 min. 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. [Description provided by NIOSH]
• Subjects:
  Animals Biomechanical Phenomena Blood Occupational Health Safety
• Keywords:
  Animal Studies Author Keywords: Traumatic Brain Injury Autoregulatory Dysfunction Biomechanical Modeling Biomechanics Blood Vessels Damage Rat Cerebral Blood Vessels TBI Traumatic Brain Injury
• ISSN:
  1878-0180
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 8 ; Utah
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  65
• NIOSHTIC Number:
  nn:20067293
• Citation:
  J Mech Behav Biomed Mater 2017 Jan; 65:627-633
• Contact Point Address:
  Kenneth L. Monson, Laboratory of Head Injury and Vessel Biomechanics, Department of Mechanical Engineering, University of Utah, 1495 E. 100 S., MEK 1550, Salt Lake City, UT, US
• Email:
  ken.monson@utah.edu
• Federal Fiscal Year:
  2017
• Performing Organization:
  University of Utah
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Journal of the Mechanical Behavior of Biomedical Materials
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2dccecc151c8e3416f924cdfdcf792c12e0b26b774fbf298ea12aa7f52f9036d81144d1685848c5f3182bfe70be15b03dcf3a9bd5531fa4ee301d063f2ceb924
• Download URL:
  https://stacks.cdc.gov/view/cdc/231393/cdc_231393_DS1.pdf
• File Type:
  [PDF - 571.56 KB ]