CLOSED-LOOP BLOOD PRESSURE CONTROL BY NEURAL STIMULATION FOR CARDIAC CARE ENVIRONMENT

 描述(申请人提供)：心脏护理环境中的血压调节，如高血压急症或心脏围手术期，主要依靠药理学方法。随着抗高血压药物的显著改进和可获得性，不受控制的血压(BP)可以在几分钟内迅速调整。然而，这些药物的适当剂量的特点是患者反应的高度变异性和较窄的可接受范围。此外，在药物引起的低血压和患者出现不想要的副作用的情况下，很难逆转药物的降压效果；因此，药物的使用受到严格的控制，并由熟练的医生监督。为了寻求新的方法来减少药物溶液的并发症，最近专注于神经刺激的研究引起了广泛的兴趣，研究和改进神经刺激策略作为控制BP的替代疗法。在我们正在进行的研究中，我们已经证明，电刺激单一的腓总神经腹侧束(VCPN)可以显著降低高血压大鼠的血压，而不会显著影响心率和呼吸。我们还注意到，刺激参数，如强度、脉冲数量和频率显著影响血压下降的幅度。基于我们有希望的初步结果，本研究的目的是研究神经刺激参数对血压的影响，以开发一种闭环控制系统。使用我们的可植入/可拆卸柔性聚合物微通道电极阵列(FlexµCEA)，我们计划通过电刺激坐骨神经或其分支(Cpn或vCPn)实现可持续的降压。为了实现这一目标，我们有两个目标：目标1.利用高血压动物模型建立可靠调节血压的神经刺激参数。将建立以下刺激参数与BP之间的定量关系：频率、脉宽、强度和各种刺激配置。这些数据将为我们提供闭环式血压控制系统所需的设计参数，从而为高血压控制提供新的治疗方式；目的2.开发一种具有实时血压监测和神经刺激的自适应闭环控制系统，以准确地调节血压。利用AIM 1的数据，将设计一个控制系统，通过FlexµCEA对目标神经实施特定的刺激方案，以保持较低的血压。在成功应用神经刺激以获得可持续降压的基础上，该项目可能实现新的高血压控制策略，有可能避免药物治疗中已知的全身副作用。

 DESCRIPTION (provided by applicant): Blood pressure modulation in a cardiac care environment such as in a hypertensive emergency or during a cardiac perioperative procedure mainly relies on pharmacological approaches. With significant improvements and availabilities in antihypertensive drugs, uncontrolled blood pressure (BP) can be rapidly modulated within minutes. However, appropriate dosing of these drugs is characterized by high variability in patient response and a narrow acceptable range. Additionally, it is very difficult to reverse the antihypertensive effect of drugs in the case of drug-induced hypotension and when patients suffer from unwanted side effects; thus, pharmaceuticals are administered under strict control with the supervision of a skilled practitioner. Seeking new approaches to reduce the complications of the pharmacological solution, recent studies focusing on nerve stimulation have generated widespread interest in investigating and refining nerve stimulation strategies as an alternative therapy for controlling BP. In our ongoing investigation, we have demonstrated that electrical stimulation of a single ventral fascicle of the common peroneal nerve (vCPN) can significantly reduce the BP of hypertensive rats without significantly effecting heart rate and respiration. We further notice that stimulation parameters such as intensity, number of pulses, and frequency significantly influence the magnitude of the BP reduction. Based on our promising initial results, the objective of this research is to investigate the effect of nerve stimulation parameters on BP in order to develop a closed-loop control system. Using our implantable/removable Flexible polymer microchannel electrode array (FlexµCEA), we plan to achieve sustainable BP reduction via electrical stimulation at the Sciatic nerve or its branch (CPN or vCPN). Towards this goal, we have two aims: Aim 1. Establish nerve stimulation parameters for reliably modulating BP using an animal model of hypertension. A quantitative relationship between the following stimulation parameters and BP will be established: frequency, pulse width, intensity, and various stimulation configurations. This data will provide for us the design parameters necessary for a closed-loop BP control system leading to new therapeutic modalities for hypertension control; Aim 2. Develop an adaptive closed-loop control system with real-time BP monitoring and neural stimulation to accurately modulate BP. Using Aim 1 data, a control system will be designed to apply a specified stimulation scheme to the target nerve through the FlexµCEA for maintaining a reduced BP. Based on the success of a closed-loop application of neural stimulation to elicit sustainable BP reduction, this project may realize new strategies for hypertension control with the potential to avoid systemic side effects known in drug-based therapies.