Extraocular Muscle (EOM) Responses to Bupivacaine Injection

布比卡因注射的眼外肌 (EOM) 反应

基本信息

批准号：
8327823
负责人：
ALAN B SCOTT
金额：
$ 60.66万
依托单位：
SMITH-KETTLEWELL EYE RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8327823
关键词：
Adult Adverse effects Affect Agonist Anesthesia procedures Anesthetics Animal Experiments Animals Bilateral Biomechanics Blepharoptosis Botox Bupivacaine Cell Nucleus Cells Characteristics Cicatrix Clinical Clinical Research Connective Tissue Contralateral Data Denervation Dimensions Disease Dose Edema Effectiveness Elasticity Electric Stimulation Electromyography Electrons Enrollment Esotropia Event Excision Eye Eye Movements Fiber Fibrosis Generations Goals Growth Factor Health Histologic Hour Human Hypertrophy Impairment In Situ In Vitro Inflammatory Injection of therapeutic agent Intramuscular Injections Laboratory Study Lead Left Length Light Local Anesthetics Longevity Magnetic Resonance Imaging Maintenance Measurement Measures Methods Microscopic Modeling Molecular Monitor Muscle Muscle Fibers Muscle function Myofibrils Myopathy Natural regeneration New Zealand Ocular orbit Operative Surgical Procedures Ophthalmology Oryctolagus cuniculus Outcome Outcome Measure Paralysed Paresis Patients Pattern Pharmaceutical Preparations Photography Plant Resins Positioning Attribute Posture Process Rattus Recovery Reporting Saccades Safety Saline Sarcomeres Secondary to Site Strabismus Stretching Surgical sutures Techniques Testing Time Tissue Preservation Tissues cell motility clinical application design dosage experience gaze human subject inclusion criteria interest muscle degeneration muscle hypertrophy nerve supply orbit muscle pilot trial prevent randomized trial repaired response satellite cell secondary outcome simulation superior rectus muscle tool trial comparing volunteer

项目摘要

Description (provided by applicant): Most existing treatments for strabismus rely on compensatory impairment of extraocular muscles (EOMs); we are developing an alternative to strengthen EOMs and alter their stiffnesses and lengths in controllable ways. Hypertrophy of fast muscle, such as EOM, is a consistent consequence of intramuscular injection of bupivacaine (BUP) in animals. BUP is a locally acting myotoxin that causes muscle fiber degeneration, satellite cell activation, and muscle fiber regeneration, continuing to hypertrophy. Inadvertent injection of BUP into human EOM during retrobulbar anesthesia causes a pattern of strabismus that modeling suggests is due to significantly increased contractility in the muscle's field of action and slightly increased stiffness affecting the opposite field. We also have preliminary results suggesting that muscles are regenerated at a length determined by eye posture during regeneration. This project aims to explore the types, amount, persistence, and mechanisms of changes in EOM after BUP injection by means of biomechanical and histological studies in rabbits, and by clinical, MR imaging, muscle force, and simulation studies in strabismus patients. We will inject BUP into normal and experimentally paralyzed rabbit eye muscles, with some eyes held in predetermined postures during regeneration. We will measure changes in muscle dimensions, elasticity, and contractile force. We will histologically assess muscle fiber counts, sizes and separations, and structural and ultrastructural changes, including scarring and fibrosis. We will vary injected volume and concentration to determine the dosage of BUP needed to safely produce beneficial effects. We have begun a pilot trial of BUP injection into EOMs of adult strabismus patients with very encouraging results in comitant horizontal cases. This will be extended to vertical and oblique muscles and to paretic disorders. We will use magnetic resonance imaging (MRI) before and at intervals after injection to verify injection sites and measure changes in muscle size. We will measure and compare binocular alignment, ocular motility, saccadic velocities, and muscle forces before and after injection, and note any side effects or complications. As data on dosage, injection technique, and safety become available and standardized, we will design a randomized trial comparing BUP injection and strabismus surgery for horizontal strabismus. Controlled muscle strengthening by BUP injection appears poised to provide a powerful and valuable new tool for strabismus management. Regenerating muscles at reduced lengths would mimic the effects of surgical resection. Regenerating muscles at increased lengths would produce effects unobtainable with surgery. Fully understanding the basic muscle changes in animal experiments and accurately documenting muscle size changes and function in patients with various disorders are both essential to this end. BUP injection also holds promise for treatment of eyelid ptosis and for muscle disorders beyond ophthalmology. PUBLIC HEALTH RELEVANCE: Injection of the local anesthetic bupivacaine can increase the size and strength, and alter the lengths of muscles. We will develop this finding as an alternative to surgical treatment for strabismus, or crossed eyes. Extension of this approach holds great promise for treatment of many muscle disorders.

描述（由申请人提供）：大多数现有的斜视治疗方法都依赖于眼外肌肉（EOM）的补偿性障碍；我们正在开发一种以可控的方式增强EOM并改变其刚度和长度的替代方法。快速肌肉（例如EOM）的肥大是动物肌内注射布比卡因（BUP）的一致结果。 BUP是一种局部作用的肌毒素，可导致肌肉纤维变性，卫星细胞活化和肌肉纤维再生，继续肥大。在骨后麻醉期间，无意将BUP注射到人EOM中会引起斜视模式，这表明建模是由于肌肉作用领域的收缩性显着增加，并且稍微增加的刚度会影响相反的场。我们还有初步的结果，表明肌肉是在再生过程中由眼姿势确定的长度再生的。该项目旨在探索通过兔子的生物力学和组织学研究以及通过临床，MR成像，肌肉力和斜视患者的仿真研究，通过生物力学和组织学研究来探索bup注射后EOM变化的类型，数量，持久性和机制。我们将将BUP注入正常和实验性瘫痪的兔眼肌，在再生过程中，有些眼睛固定在预定的姿势中。我们将衡量肌肉维度，弹性和收缩力的变化。我们将在组织学上评估肌肉纤维计数，大小和分离，以及结构和超微结构的变化，包括疤痕和纤维化。我们将改变注入的体积和浓度，以确定安全产生有益效果所需的BUP剂量。我们已经开始对成年斜视患者的EOM注射BUP的试点试验，并在水平病例中取得了非常令人鼓舞的结果。这将扩展到垂直和倾斜的肌肉以及偏向性疾病。我们将在注射后和间隔使用磁共振成像（MRI）来验证注射部位并测量肌肉大小的变化。我们将测量和比较注射前后的双眼比对，眼运动性，saccadic速度和肌肉力，并注意任何副作用或并发症。随着有关剂量，注射技术和安全性的数据，我们将设计一项随机试验，以比较BUP注射和斜视手术的水平斜视手术。通过注射BUP的控制肌肉加强似乎有望为斜视管理提供强大而有价值的新工具。减少长度的再生肌肉会模仿手术切除的作用。长度增加的肌肉再生会产生手术无法获得的影响。充分了解动物实验的基本肌肉变化，并准确地记录各种疾病患者的肌肉大小的变化和功能，这对于这一目的都是必不可少的。 BUP注射还有望治疗眼睑ptosis和眼科以外的肌肉疾病。公共卫生相关性：注射局部麻醉二维卡因可以增加大小和力量，并改变肌肉的长度。我们将开发这一发现，以替代斜视或越眼睛的手术治疗。这种方法的扩展对治疗许多肌肉障碍有很大的希望。