Short-term remote ischemic conditioning may protect monkeys after ischemic stroke

Ann Clin Transl Neurol. 2019 Jan 15;6(2):310-323. doi: 10.1002/acn3.705. eCollection 2019 Feb.

Abstract

Objective: We aimed to evaluate the safety and effectiveness of short-term remote ischemic postconditioning (RIPC) in acute stroke monkey models.

Methods: Acute stroke monkeys were allocated to four groups based on the number of limbs exposed to RIPC. RIPC was initiated by 5-min cuff inflation/deflation cycles of the target limb(s) for 5-10 bouts. Vital signs, skin integrity, brain MRI, and serum levels of cardiac enzymes (myoglobin, creatine kinase [CK], CK-muscle/brain [CK-MB]), one inflammatory marker (high-sensitivity C-reactive protein [hsCRP], and one endothelial injury marker (von Willebrand factor [vWF]) were assessed. Spetzler scores were used to assess neurological function.

Results: No significant differences in vital signs or local skin integrity were found. Short-term RIPC did not reduce infarct volume under any condition at the 24th hour after stroke. However, neurological function improved in multi-limb RIPC compared with sham and single-limb RIPC at the 30th day follow-up after stroke. Myoglobin, CK, and CK-MB levels were reduced after multi-limb RIPC, regardless of the number of bouts. Moreover, multi-limb RIPC produced a greater diminution in CK-MB levels, whereas two-limb RIPC was more effective in reducing serum CK levels at the 24th hour after stroke. hsCRP increased after 5 bouts of multi-limb RIPC before decreasing below baseline and single-limb RIPC levels. Serum vWF was decreased at later time points after RIPC in all RIPC groups.

Conclusions: Stroke monkeys in hyperacute stage may benefit from short-term RIPC; however, whether this intervention can be translated into clinical use in patients with acute ischemic stroke warrants further study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Brain Ischemia / physiopathology*
  • Creatine Kinase, MB Form / blood
  • Extremities / physiopathology*
  • Haplorhini
  • Ischemia / physiopathology
  • Ischemic Postconditioning*
  • Male
  • Myocardial Reperfusion Injury / blood
  • Myocardial Reperfusion Injury / physiopathology
  • Stroke / physiopathology*

Substances

  • Biomarkers
  • Creatine Kinase, MB Form

Grants and funding

This work was funded by National Key R&D Program grant 2017YFC1308401; National Natural Science Foundation grant 81371289; Project of Beijing Municipal Top Talent for Healthy Work grant 2014‐2‐015.