Gooneratne Thushan Dhananja, Homer-Vanniasinkam Shervanthi, Wijeyaratne Serosha Mandika
Department of Vascular Surgery, University of Colombo, Colombo, Sri Lanka.
Department of Vascular Surgery, The General Infirmary at Leeds, Leeds, UK, 3Department of Surgery, University of Colombo, Colombo, Sri Lanka.
Vasc Specialist Int. 2022 Sep 30;38:28. doi: 10.5758/vsi.220018.
Exaggerated leucocyte activity is a crucial step in the pathophysiology of skeletal muscle ischemia-reperfusion injury (IRI). We tested the hypothesis that insulin, via its' anti-leukocyte activity, attenuates skeletal muscle IRI in humans.
This randomized, blinded, placebo-controlled trial was conducted in patients with skeletal muscle ischemia who required revascularization. Treatment protocols were similar among them except for the insulin group, which received an infusion of insulin at 2.5 U/h. The degree of endothelial adhesiveness; leukocyte activity and pro-inflammatory status via P-selectin, tumor necrosis factor (TNF)-alpha, and myeloperoxidase (MPO) levels in the venous effluent; and clinical outcomes were measured.
Twenty-four consenting patients were randomized to the insulin or control group. There were no significant differences between the two groups except for the median serum insulin level, which was higher in the insulin group (P<0.01). No serious intervention-related adverse events were observed. P-selectin (55.04-99.86 pg/mL; P<0.001), MPO (110.8-160.6 pg/mL; P<0.001), and TNF-alpha (12.16-36.01 pg/mL; P<0.001) levels demonstrated a significant increase post-reperfusion in the 'control' group, reaching a peak value at 2 hours post-reperfusion. The increase in all three markers from baseline was significantly diminished in the insulin group at the two-hour (P-selectin, P=0.001; MPO, P=0.001; TNF-alpha, P=0.005) and four-hour (P-selectin, P=0.003; MPO, P=0.002; TNF-alpha, P=0.01) intervals. The differences in clinical outcomes between the insulin and control groups were not statistically significant.
In clinical practice, insulin has the potential to attenuate the severity of skeletal muscle IRI inhibiting P-selectin, MPO, and TNF-alpha levels.
白细胞活性过度增强是骨骼肌缺血再灌注损伤（IRI）病理生理学中的关键步骤。我们检验了如下假设：胰岛素通过其抗白细胞活性减轻人类骨骼肌IRI。
本随机、双盲、安慰剂对照试验在需要血管重建的骨骼肌缺血患者中进行。除胰岛素组以2.5 U/h的速度输注胰岛素外，各治疗方案相似。测量内皮黏附程度；通过静脉流出液中P-选择素、肿瘤坏死因子（TNF）-α和髓过氧化物酶（MPO）水平评估白细胞活性和促炎状态；并评估临床结局。
24名同意参与的患者被随机分为胰岛素组或对照组。除胰岛素组的血清胰岛素中位数水平较高外（P<0.01），两组之间无显著差异。未观察到严重的干预相关不良事件。“对照组”中，再灌注后P-选择素（55.04 - 99.86 pg/mL；P<0.001）、MPO（110.8 - 160.6 pg/mL；P<0.001）和TNF-α（12.16 - 36.01 pg/mL；P<0.001）水平显著升高，在再灌注后2小时达到峰值。胰岛素组在两小时（P-选择素，P = 0.001；MPO，P = 0.001；TNF-α，P = 0.005）和四小时（P-选择素，P = 0.003；MPO，P = 0.002；TNF-α，P = 0.01）时，这三种标志物从基线的升高幅度均显著减小。胰岛素组和对照组之间的临床结局差异无统计学意义。
在临床实践中，胰岛素有可能通过抑制P-选择素、MPO和TNF-α水平来减轻骨骼肌IRI的严重程度。
