Naraoka Masato, Shimamura Norihito, Ohkuma Hiroki
Department of Advanced Emergency and Disaster Medical Center, Hirosaki University School of Medicine & Hospital, 53 Honcho, Hirosaki, 036-8563, Japan.
Department of Neurosurgery, Hirosaki General Medical Center, Hirosaki, Japan.
Transl Stroke Res. 2024 Nov 20. doi: 10.1007/s12975-024-01308-y.
Cilostazol, a phosphodiesterase 3 (PDE3) inhibitor that exerts antiplatelet effects, has therapeutic potential for delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, its mechanism of action remains unclear. We hypothesized that cilostazol alleviates DCI by improving cerebral microcirculatory dysfunction, which is a component of early brain injury. To test this hypothesis, we analyzed the intracerebral circulation time (iCCT) in 256 patients with aSAH from two randomized controlled trials (74 received cilostazol, 54 received pitavastatin, and 128 were controls). A minority of patients (n = 72, 28%) developed severe angiographic vasospasm (aVS) and DCI (n = 42, 16%) and had poor outcomes (n = 35, 14%). We measured iCCT as the time to peak in the ultraearly phase (baseline) and the subacute phase or at DCI onset (follow-up). The cilostazol group had shorter follow-up iCCT and larger iCCT differences than the other groups, indicating improved microcirculatory function, particularly in patients with DCI and poor outcomes. Multivariate analysis revealed that cilostazol treatment is a significant predictor of favorable outcomes, whereas DCI occurrence, a decrease in iCCT differences, and high clinical severity (Hunt & Hess grades 3-4) were associated with poor outcomes. Diminished microcirculatory dysfunction may alleviate DCI and improve outcomes among patients with aSAH following cilostazol treatment. Further research is warranted to confirm these findings and explore the dose-dependent effects of cilostazol on the microcirculatory function.
西洛他唑是一种具有抗血小板作用的磷酸二酯酶3（PDE3）抑制剂，对动脉瘤性蛛网膜下腔出血（aSAH）后的迟发性脑缺血（DCI）具有治疗潜力。然而，其作用机制尚不清楚。我们假设西洛他唑通过改善脑微循环功能障碍来缓解DCI，而脑微循环功能障碍是早期脑损伤的一个组成部分。为了验证这一假设，我们分析了来自两项随机对照试验的256例aSAH患者的脑内循环时间（iCCT）（74例接受西洛他唑治疗，54例接受匹伐他汀治疗，128例为对照组）。少数患者（n = 72，28%）发生严重血管造影血管痉挛（aVS）和DCI（n = 42，16%），预后较差（n = 35，14%）。我们将iCCT测量为超早期（基线）和亚急性期或DCI发作时（随访）达到峰值的时间。与其他组相比，西洛他唑组的随访iCCT更短，iCCT差异更大，表明微循环功能得到改善，尤其是在发生DCI和预后较差的患者中。多变量分析显示，西洛他唑治疗是良好预后的重要预测因素，而DCI的发生、iCCT差异的减小和高临床严重程度（Hunt & Hess 3 - 4级）与不良预后相关。微循环功能障碍的减轻可能会缓解DCI，并改善西洛他唑治疗后aSAH患者的预后。有必要进行进一步的研究来证实这些发现，并探索西洛他唑对微循环功能的剂量依赖性效应。
