Mattingly Thomas K, McDavid Andrew, Wolf Amparo, Lieber Glen, Solar Ronald, Lee Donald, Lownie Stephen P
Department of Neurosurgery, University of Rochester, Rochester, NY, United States.
Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, United States.
Front Neurol. 2022 Apr 25;13:874701. doi: 10.3389/fneur.2022.874701. eCollection 2022.
Hypothermia remains the best studied neuroprotectant. Despite extensive positive large and small animal data, side effects continue to limit human applications. Selective hypothermia is an efficient way of applying neuroprotection to the brain without the systemic complications of global hypothermia. However, optimal depth and duration of therapeutic hypothermia are still unknown. We analyzed a large animal cohort study of selective hypothermia for statistical relationships between depth or duration of hypothermia and the final stroke volume.
A cohort of 30 swine stroke subjects provided the dataset for normothermic and selective hypothermic animals. Hypothermic parameters including duration, temperature nadir, and an Area Under the Curve measurement for 34 and 30°C were correlated with the final infarct volumes measured by MRI and histology.
Between group comparisons continue to demonstrate a reduction in infarct volume with selective hypothermia. Histologically-derived infarct volumes were 1.2 mm smaller in hypothermia-treated pigs ( = 0.04) and showed a similar, but non-significant reduction in MRI ( = 0.15). However, within the selective hypothermia group, more intense cooling, as measured through increased AUC 34 and decreased temperature nadir was associated with larger infarct proportions by MRI [Pearson's = 0.48 ( = 0.05) and = -0.59 ( = 0.01), respectively]. Reevaluation of the entire cohort with quadratic regression demonstrated a U-shaped pattern, wherein the average infarct proportion was minimized at 515 degree-minutes (AUC34) of cooling, and increased thereafter. In a single case of direct brain tissue oxygen monitoring during selective hypothermia, brain tissue oxygen strongly correlated with brain temperature reduction over the course of selective hypothermia to 23°C.
In a large animal model of selective hypothermia applied to focal ischemia, there is a non-monotone relationship between duration and depth of hypothermia and stroke volume reduction. This suggests a limit to depth or duration of selective hypothermia for optimal neuroprotection. Further research is required to delineate more precise depth and duration limits for selective hypothermia.
低温仍然是研究最为充分的神经保护剂。尽管在大型和小型动物实验中都获得了大量积极的数据，但副作用仍然限制了其在人类中的应用。选择性低温是一种在不产生全身低温并发症的情况下对大脑实施神经保护的有效方法。然而，治疗性低温的最佳深度和持续时间仍然未知。我们分析了一项关于选择性低温的大型动物队列研究，以探究低温的深度或持续时间与最终中风体积之间的统计关系。
30头猪中风实验对象组成的队列提供了正常体温和选择性低温动物的数据集。低温参数，包括持续时间、最低温度以及34°C和30°C时的曲线下面积测量值，与通过MRI和组织学测量的最终梗死体积相关。
组间比较继续表明选择性低温可减少梗死体积。经组织学得出的梗死体积在低温治疗的猪中要小1.2立方毫米（P = 0.04），在MRI测量中显示出类似但不显著的减少（P = 0.15）。然而，在选择性低温组内，通过增加的34°C曲线下面积和降低的最低温度所衡量的更强冷却与MRI显示的更大梗死比例相关[皮尔逊相关系数分别为0.48（P = 0.05）和 -0.59（P = 0.01）]。用二次回归对整个队列进行重新评估显示出一种U形模式，其中平均梗死比例在515度 - 分钟（34°C曲线下面积）的冷却时最小化，此后增加。在选择性低温期间直接进行脑组织氧监测的一个案例中，在选择性低温至23°C的过程中，脑组织氧与脑温降低密切相关。
在应用于局灶性缺血的选择性低温大型动物模型中，低温的持续时间和深度与中风体积减少之间存在非单调关系。这表明选择性低温的深度或持续时间对于最佳神经保护存在限制。需要进一步研究来确定选择性低温更精确的深度和持续时间限制。
