Department of Neurology, Dubrava University Hospital, Zagreb, Croatia.
Department of Physiology and Immunology, Faculty of Medicine Osijek, University Josip, Juraj Strossmayer, Osijek, Croatia.
Diabetes Res Clin Pract. 2013 Jul;101(1):81-7. doi: 10.1016/j.diabres.2013.04.004. Epub 2013 May 15.
Impaired cerebral vasoreactivity to endothelium-dependent stimuli were described in type 2 diabetes mellitus (T2DM), but the mechanisms underlying that impairment are still unclear. The aim of this study was to investigate the role of cyclooxygenases' metabolites in response to acute hypercapnic stimulus in cerebral vessels, in patients with T2DM.
Vascular responses in the breath-holding test (BHT) were assessed in the absence/presence of a non-selective, reversible-inhibitor of cyclooxygenases, indomethacin (INDO), by functional transcranial Doppler sonography of the middle cerebral artery (N of patients=50; 33 men and 17 women). The functional hemodynamic parameter mean flow velocity (MFV) was assessed at rest, before and 90min after 100mg of INDO, and during the BHT. Breath holding index (BHI) [(MFV at the end of BHT minus MFV at rest)/MFV at rest)×100/s of breath-holding] was calculated after BHT performed before and 90min after INDO.
MFV at rest significantly decreased after INDO administration compared with a control condition before INDO (at rest before INDO from 49.36±15.09 to 36.72±8.45 after INDO, p<0.001) However, overall cerebral vessel vasoreactivity to hypercapnia, evaluated with BHI, was significantly improved after INDO administration compared with the BHI before INDO administration (from 0.68±0.4 to 1.27±0.42, p<0.001).
The improvement in cerebral vasoreactivity in response to BHT after INDO administration suggests that the production of a vasoconstrictor metabolite of cyclooxygenase in diabetic patients was reduced by indomethacin consumption.
在 2 型糖尿病(T2DM)患者中,描述了内皮依赖性刺激物引起的脑血管反应性受损,但这种损伤的机制尚不清楚。本研究旨在探讨环氧化酶代谢物在 T2DM 患者急性高碳酸血症刺激下对脑血管反应的作用。
通过功能 transcranial 多普勒超声检查大脑中动脉(患者 N=50;33 名男性和 17 名女性),在无/存在非选择性、可逆性环氧化酶抑制剂吲哚美辛(INDO)的情况下,评估呼吸暂停试验(BHT)中的血管反应。在 INDO 之前和之后的 90 分钟,评估休息时、之前和之后的平均血流速度(MFV),并在 BHT 期间评估。在 INDO 之前和之后的 90 分钟进行 BHT 后,计算呼吸暂停指数(BHI)[(BHT 结束时的 MFV-休息时的 MFV)/MFV 休息时×100/s 呼吸暂停]。
与 INDO 之前的对照条件相比,INDO 给药后休息时的 MFV 显著降低(INDO 之前的休息时从 49.36±15.09 降至 INDO 后的 36.72±8.45,p<0.001)。然而,与 INDO 给药前的 BHI 相比,通过 INDO 给药后整体脑血管对高碳酸血症的反应性(通过 BHI 评估)显著改善(从 0.68±0.4 增加至 1.27±0.42,p<0.001)。
INDO 给药后 BHT 引起的脑血管反应性改善表明,糖尿病患者中环氧化酶缩血管代谢物的产生因吲哚美辛的消耗而减少。