Modeling and Assessment of Cerebrovascular Autoregulation

描述(申请人提供)：头部损伤患者容易发生继发性并发症，可能包括脑肿胀、脑循环障碍和脑缺血。这项工作的目标是模拟脑血流主动和被动调节的生物力学机制。该模型将为持续评估脑损伤患者脑血管自动调节的方法提供基础，从而允许改进重症监护管理和治疗。当自我调节完整时，脑血管床会因脑灌流压(CPP)的升高和降低而收缩和扩张。当自我调节受损时，脑血管床内血管管径的变化被动地跟随CPP的变化。最近，我们将系统辨识建模技术应用于实验室和临床记录的颅内压和动脉血压(ABP)，以检测脑血管压力传递的最高模式频率(HMF)的变化。根据对这些压力记录的分析结果，提出了以下假设：当自我调节完整时，HMF的变化与脑灌流压(CPP)和动脉-小动脉床阻力的变化成反比。相反，当脑血管张力处于被动状态时，HMF的变化与CPP和动脉-小动脉床阻力的变化直接相关。为了验证这一假设，将使用仔猪来实现以下三个具体目标。以开颅窗的仔猪为研究对象，测定动脉血气调节正常和压力调节受损时小动脉内径的变化、激光多普勒和氢清除法测定脑血流量、CPP与HMF的关系。此外，我们将确定在人工升高的ABP过程中不适当的血管扩张引起的变化的这些相同的关系。采用三阶Windkesel颅内压动力学模型模拟颅内压，研究脑血流主动和被动调节的生物力学机制。

DESCRIPTION (provided by applicant): Patients with head-injury tend to develop secondary complications that may include brain swelling, impaired cerebral circulation, and cerebral ischemia. The goal of this work is to model the biomechanical mechanisms underlying active and passive regulation of cerebral blood flow. This model will provide the basis for a method to continuously assess cerebrovascular autoregulation of patients with brain injury, thereby permitting improved intensive care management and therapy. When autoregulation is intact, the cerebrovascular bed constricts and dilates in response to increases and decreases of cerebral perfusion pressure (CPP). When autoregulation is impaired, changes in the caliber of vessels within the cerebrovascular bed passively follow changes of CPP. Recently, we have applied system identification modeling techniques to laboratory and clinical recordings of ICP and arterial blood pressure (ABP) to examine changes in the highest modal frequency (HMF) of cerebrovascular pressure transmission. From findings based on an analysis of these pressure recordings, the following hypothesis has been developed: When autoregulation is intact, changes of the HMF are inversely related to changes of cerebral perfusion pressure (CPP) and resistance of the arterial-arteriolar bed. In contrast, when cerebrovascular tension is passive, changes of HMF are directly related to changes of CPP and resistance of the arterial-arteriolar bed. To test this hypothesis, the following three specific aims will be addressed using piglets. Using the piglet equipped with a cranial window, we will determine the relationships between changes of arteriolar diameter, cerebral blood flow measured by laser Doppler and by hydrogen clearance method, CPP, and the HMF during intact and impaired pressure regulation induced by manipulation of arterial blood gases. Furthermore, we will determine these same relationships for changes induced by inappropriate vasodilation during artificially elevated ABP. Simulation of ICP with a third order windkessel model of intracranial pressure dynamics will be used to examine the biomechanical mechanisms underlying active and passive regulation of cerebral blood flow.