Polak Anna, Kloth Luther C, Paczula Malgorzata, Nawrat-Szoltysik Agnieszka, Kucio Ewa, Manasar Ahmed, Blaszczak Edward, Janikowska Grazyna, Mazurek Urszula, Malecki Andrzej, Kucio Cezary
Academy of Physical Education, Katowice, Poland.
Marquette University, Milwaukee, WI.
Wound Manag Prev. 2019 Nov;65(11):19-32.
It remains unclear whether electrical currents can affect biological factors that determine chronic wound healing in humans.
The aim of this study was to determine whether anodal and cathodal high-voltage monophasic pulsed currents (HVMPC) provided to the area of a pressure injury (PI) change the blood level of cytokines (interleukin [IL]-1β, IL-10, and tumor necrosis factor [TNF]-α) and growth factors (insulin-like growth factor [IGF]-1 and transforming growth factor [TGF]-β1) in patients with neurological injuries and whether the level of circulatory cytokines and growth factors correlates with PI healing progression.
This study was part of a randomized clinical trial on the effects of HVMPC on PI healing. All patients with neurological injuries (spinal cord injury, ischemic stroke, and blunt trauma to the head) and a stage 2, stage 3, or stage 4 PI of at least 4 weeks' duration hospitalized in one rehabilitation center were eligible to participate if older than 18 years of age and willing to consent to donating blood samples. Exclusion criteria included local contraindications to electrical stimulation (cancer, electronic implants, osteomyelitis, tunneling, necrotic wounds), PIs requiring surgical intervention, patients with poorly controlled diabetes mellitus (HbA1C > 7%), critical wound infection, and/or allergies to standard wound treatment. Participants were randomly assigned to 1 of 3 groups: anodal (AG) or cathodal (CG) HVMPC treatment (154 μs; 100 Hz; 360 µC/sec; 1.08 C/day) or a placebo (PG, sham) applied for 50 minutes a day, 5 days per week, for 8 weeks. TNF-α, IL-1β, IL-10, TGF-β1, and IGF-1 levels in blood serum were assessed using the immunoenzyme method (ELISA) and by chemiluminescence, respectively, at baseline and week 4. Wound surface area measurements were obtained at baseline and week 4 and analyzed using a digitizer connected to a personal computer. Statistical analyses were performed using the maximum-likelihood chi-squared test, the analysis of variance Kruskal-Wallis test, the Kruskal-Wallis post-hoc test, and Spearman's rank order correlation; the level of significance was set at P ≤.05.
Among the 43 participants, 15 were randomized to AG (mean age 53.87 ± 13.30 years), 13 to CG (mean age 51.08 ± 20.43 years), and 15 to PG treatment (mean age 51.20 ± 14.47 years). Most PIs were located in the sacral region (12, 74.42%) and were stage 3 (11, 67.44%). Wound surface area baseline size ranged from 1.00 cm2 to 58.04 cm2. At baseline, none of the variables were significantly different. After 4 weeks, the concentration of IL-10 decreased in all groups (AG: 9.8%, CG: 38.54%, PG: 27.42%), but the decrease was smaller in the AG than CG group (P = .0046). The ratio of pro-inflammatory IL-10 to anti-inflammatory TNF-α increased 27.29% in the AG and decreased 26.79% in the CG and 18.56% in the PG groups. Differences between AG and CG and AG and PG were significant (AG compared to CG, P = .0009; AG compared to PG, P = .0054). Other percentage changes in cytokine and growth factor concentration were not statistically significant between groups. In the AG, the decrease of TNF-α and IL-1β concentrations correlated positively with the decrease of PI size (P <.05).
Anodal HVMPC elevates IL-10/TNF-α in blood serum. The decrease of TNF-α and IL-1β concentrations in blood serum correlates with a decrease of PI wound area. More research is needed to determine whether the changes induced by anodal HVMPC improve PI healing and to determine whether and how different electrical currents affect the activity of biological agents responsible for specific wound healing phases, both within wounds and in patients' blood. In clinical practice, anodal HVMPC should be used to increase the ratio of anti-inflammatory IL-10 to pro-inflammatory TNF-α , which may promote healing.
电流是否会影响决定人类慢性伤口愈合的生物学因素尚不清楚。
本研究的目的是确定施加于压力性损伤（PI）区域的阳极和阴极高压单相脉冲电流（HVMPC）是否会改变神经损伤患者细胞因子（白细胞介素[IL]-1β、IL-10和肿瘤坏死因子[TNF]-α）和生长因子（胰岛素样生长因子[IGF]-1和转化生长因子[TGF]-β1）的血液水平，以及循环中的细胞因子和生长因子水平是否与PI愈合进程相关。
本研究是关于HVMPC对PI愈合影响的随机临床试验的一部分。所有在一个康复中心住院、年龄大于18岁且愿意同意捐献血样的神经损伤（脊髓损伤、缺血性中风和头部钝器伤）患者，且患有持续至少4周的2期、3期或4期PI者均符合参与条件。排除标准包括电刺激的局部禁忌证（癌症、电子植入物、骨髓炎、窦道形成、坏死性伤口）、需要手术干预的PI、糖尿病控制不佳（糖化血红蛋白>7%）的患者、严重伤口感染和/或对标准伤口治疗过敏。参与者被随机分配到3组中的1组：阳极（AG）或阴极（CG）HVMPC治疗（154微秒；100赫兹；360微库仑/秒；1.08库仑/天）或安慰剂（PG，假刺激），每天应用50分钟，每周5天，共8周。在基线和第4周时，分别使用免疫酶法（ELISA）和化学发光法评估血清中TNF-α、IL-1β、IL-10、TGF-β1和IGF-1的水平。在基线和第4周时获取伤口表面积测量值，并使用连接到个人计算机的数字化仪进行分析。使用最大似然卡方检验、方差分析的Kruskal-Wallis检验、Kruskal-Wallis事后检验和Spearman等级相关进行统计分析；显著性水平设定为P≤0.05。
在43名参与者中，15人被随机分配到AG组（平均年龄53.87±13.30岁），13人被随机分配到CG组（平均年龄51.08±20.43岁），15人被随机分配到PG治疗组（平均年龄51.20±14.47岁）。大多数PI位于骶尾部（12处，74.42%），且为3期（11处，67.44%）。伤口表面积基线大小范围为1.00平方厘米至58.04平方厘米。在基线时，所有变量均无显著差异。4周后，所有组中IL-10的浓度均下降（AG组：9.8%，CG组：38.54%，PG组：27.42%），但AG组的下降幅度小于CG组（P = 0.0046）。促炎IL-10与抗炎TNF-α的比值在AG组中增加了27.29%，在CG组中下降了26.79%，在PG组中下降了18.56%。AG组与CG组以及AG组与PG组之间的差异具有显著性（AG组与CG组相比，P = 0.0009；AG组与PG组相比，P = 0.0054）。细胞因子和生长因子浓度的其他百分比变化在组间无统计学意义。在AG组中，TNF-α和IL-1β浓度的下降与PI大小的减小呈正相关（P<0.05）。
阳极HVMPC可提高血清中IL-10/TNF-α的水平。血清中TNF-α和IL-1β浓度的下降与PI伤口面积减小相关。需要更多研究来确定阳极HVMPC引起的变化是否能改善PI愈合，以及确定不同电流是否以及如何影响负责特定伤口愈合阶段的生物因子在伤口内和患者血液中的活性。在临床实践中，应使用阳极HVMPC来提高抗炎IL-10与促炎TNF-α的比值，这可能促进愈合。
