Abstract
ObjectiveRecent studies have demonstrated the positive roles of remote ischemic conditioning (RIC) in patients with cerebrovascular diseases; however, the mechanisms remain unclear. This study aimed to explore the effect of serial RIC on dynamic cerebral autoregulation (dCA) and serum biomarkers associated with brain injury, both of which are related to the prognosis of cerebrovascular disease.MethodsThis was a self-controlled interventional study in healthy adults. The RIC was conducted twice a day for 7 consecutive days (d1–d7) and comprised 4 × 5-min single arm cuff inflation/deflation cycles at 200 mmHg. All participants underwent assessments of dCA ten times, including baseline, d1, d2, d4, d7, d8, d10, d14, d21, and d35 of the study. Blood samples were collected four times (baseline, d1, d7, and d8) immediately after dCA measurements. The transfer function parameters [phase difference (PD) and gain] were used to quantify dCA. Four serum biomarkers associated with brain injury, ubiquitin C-terminal hydrolase-L1, neuron-specific enolase, glial fibrillary acidic protein, and S100β were tested.ResultsTwenty-two healthy adult volunteers (mean age 25.73 ± 1.78 years, 3 men [13.6%], all Asian) were enrolled in this study. Bilateral PD values were significantly higher since four times of RIC were completed (d2) compared with PD values at baseline (left: 53.31 ± 10.53 vs. 45.87 ± 13.02 degree, p = 0.015; right: 54.90 ± 10.46 vs. 45.96 ± 10.77 degree, p = 0.005). After completing 7 days of RIC, the significant increase in dCA was sustained for at least 28 days (d35, left: 53.11 ± 14.51 degree, P = 0.038; right: 56.95 ± 14.57 degree, p < 0.001). No difference was found in terms of different serum biomarkers related to brain injury before and after RIC.ConclusionThe elevation in dCA was detected immediately after four repeated times of RIC, and 7-day consecutive RIC induced a sustained increase in dCA for at least 28 days and did not affect blood biomarkers of brain injury in healthy adults. These results will help us to formulate detailed strategies for the safe and effective application of RIC in patients with cerebrovascular disease.
Highlights
Remote ischemic conditioning (RIC) refers to an intervention that offers remote tissues and organs a resistance capacity to ischemia/reperfusion injury through small doses of reversible episodes of ischemia and reperfusion (Hess et al, 2015; Heusch et al, 2015) that activate neurogenic pathways, humoral factors, and the immune system (Anrather and Hallenbeck, 2013)
Thirty-six healthy adult volunteers were assessed for eligibility, and six participants who declined to participate, met the exclusion criteria, or were intolerant to RIC were excluded
Phase difference (PD) values were significantly higher since four times of RIC were completed compared with PD values at baseline
Summary
Remote ischemic conditioning (RIC) refers to an intervention that offers remote tissues and organs a resistance capacity to ischemia/reperfusion injury through small doses of reversible episodes of ischemia and reperfusion (Hess et al, 2015; Heusch et al, 2015) that activate neurogenic pathways, humoral factors, and the immune system (Anrather and Hallenbeck, 2013). Recent studies have demonstrated that RIC could increase cerebral perfusion, promote hematoma resolution, facilitate recovery of nerve function, and improve the clinical prognosis of patients with cerebrovascular diseases (Meng et al, 2012; An et al, 2020; Zhao et al, 2021). Our previous study found that dynamic cerebral autoregulation (dCA), an important indicator of cerebrovascular function which related to the prognosis of cerebrovascular disease (Xiong et al, 2017) was improved after once round of RIC (Guo et al, 2019); the exact effect of serial RIC on dCA was unclear. The dCA alteration period after serial RIC remains unknown. Solving these problems will help us to formulate detailed strategies for the safe and effective application of RIC in patients with cerebrovascular disease
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