Zibly Zion, Fein Lory, Sharma Mayur, Assaf Yaron, Wohl Anton, Harnof Sagi
Department of Neurosurgery, The Chaim Sheba Medical Center, Tel Hashomer, Israel.
Rose-Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, Ohio, 44195, USA.
Neurol India. 2017 Sep-Oct;65(5):1035-1042. doi: 10.4103/neuroindia.NI_357_16.
One of the most serious complications following subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI) secondary to symptomatic vasospasm. An animal model mimicking post SAH vasospasm is essential for enabling the translation of newer technologies from the conceptual phase to animal studies, and eventually to clinical trials. Various animal models of DCI following SAH have been reported, with canine models being the most common. Due to the similarity of the swine cardiovascular system and its dimensions to the human's system, the main objective of this study was to establish a consistent and quantitatively representative model of SAH-induced vasospasm in swine.
Twelve female swines (57 ± 3 kg) were injected twice (with a 2-day interval between injections) with autologous blood into the subarachnoid space at the level of C2-3 vertebrae. Different volumes were injected to identify clinical and radiological changes. The effect of volume variations on hematoma size and vasospasm intensity in the circle of Willis arteries were studied 7-14 days after the first injection using ascending pharyngeal angiographic measurements of vessel diameter. Neurological outcome using a modified scoring table based on clinical parameters (e.g., appetite, behavior, walking, posture, and eye movement) was recorded.
Our results demonstrate that between volume combinations, intrathecal injection of 12 ml followed by 15 ml, with a 2-day interval in between, resulted in the most extensive angiographically-assessed vasospasm 12 ± 2 days following the first injection. The degree of vasospasm in the intracranial internal carotid artery was 22% and 16% for the left and right sides, respectively. Vasoconstriction of the anterior cerebral artery was 34% and 27% for the left and right sides, respectively. The vasoconstriction was not associated with either overt clinical signs or clinical outcome, which is indicative of an ischemic event.
The relative scarcity of swine models for SAH-induced vasospasm motivated us to develop and quantify a straightforward protocol for producing consistent mild-to-moderate vasospasm following SAH. As swine is commonly used in translational cardiovascular research, we believe that this study constitutes an important phase in the study of SAH and in developing pharmacological agents and medical devices for interventions.
蛛网膜下腔出血（SAH）后最严重的并发症之一是继发于症状性血管痉挛的迟发性脑缺血（DCI）。一种模拟SAH后血管痉挛的动物模型对于使新技术从概念阶段转化为动物研究，并最终转化为临床试验至关重要。已经报道了各种SAH后DCI的动物模型，其中犬类模型最为常见。由于猪的心血管系统及其尺寸与人类系统相似，本研究的主要目的是建立一种在猪身上诱导SAH后血管痉挛的一致且具有定量代表性的模型。
12只雌性猪（体重57±3千克）在C2-3椎体水平的蛛网膜下腔分两次（注射间隔2天）注射自体血。注射不同体积以确定临床和影像学变化。在首次注射后7-14天，使用咽升动脉血管造影测量血管直径，研究体积变化对Willis动脉环血肿大小和血管痉挛强度的影响。使用基于临床参数（如食欲、行为、行走、姿势和眼球运动）的改良评分表记录神经学结果。
我们的结果表明，在不同体积组合中，鞘内注射12毫升后间隔2天再注射15毫升，在首次注射后12±2天导致血管造影评估的最广泛血管痉挛。颅内颈内动脉左侧和右侧的血管痉挛程度分别为22%和16%。大脑前动脉左侧和右侧的血管收缩分别为34%和27%。血管收缩与明显的临床体征或临床结果均无关，这表明存在缺血事件。
用于SAH诱导血管痉挛的猪模型相对较少，促使我们开发并量化一种简单的方案，以在SAH后产生一致的轻度至中度血管痉挛。由于猪常用于转化心血管研究，我们认为本研究是SAH研究以及开发用于干预的药物和医疗器械的重要阶段。
