Bell E David, Donato Anthony J, Monson Kenneth L
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.
Department of Internal Medicine, Division of Geriatrics, University of Utah, Salt Lake City, UT, USA.
J Mech Behav Biomed Mater. 2017 Jan;65:627-633. doi: 10.1016/j.jmbbm.2016.09.028. Epub 2016 Sep 22.
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 1.2λ or 1.3λ at strain rates of 0.2 or 20s. 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*λ. 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.
脑血管对于维持大脑健康至关重要。创伤性脑损伤（TBI）通常会导致自动调节功能障碍以及脑血管无法维持大脑内的稳态。虽然已知损伤后脑生物化学变化会导致这种功能障碍，但组织变形也可能直接改变血管平滑肌细胞（SMC）的功能。作为理解拉伸诱导功能障碍的第一步，本研究调查了过度拉伸对大脑中动脉（MCA）中SMC收缩行为的影响。我们假设血管功能在拉伸和应变率阈值以上会发生改变。对来自Sprague Dawley大鼠的24条MCA进行了测试。在基础SMC张力形成后，血管接受等渗细胞外钾（K）水平的增加。然后将样本以0.2或20s的应变率进行1.2λ或1.3λ的轴向过度拉伸。过度拉伸后，立即和过度拉伸60分钟后再次测量SMC收缩行为。对照血管接受相同的方案，但不进行过度拉伸。使用相对于完全扩张内径的收缩百分比（%C）和引发半数最大收缩反应所需的K剂量（EC50）来表征SMC收缩行为。对照血管在连续的表征测试中对K的敏感性增加，因此所有效应均相对于时间匹配的对照反应进行量化。样本对细胞外K表现出典型的双相反应，分别对小和大的K浓度做出舒张和收缩反应。如假设的那样，轴向过度拉伸改变了SMC收缩行为，表现为亚最大收缩K剂量的%C降低（p<0.05）和EC50增加（p<0.01），但仅在快速拉伸至1.3*λ的测试组中。虽然%C的变化仅在过度拉伸后立即有显著差异，但EC50的变化持续了60分钟。这些结果表明，变形可改变SMC收缩行为，因此可能在与TBI后脑内病理化学环境无关的脑血管自动调节功能障碍中起作用。
