Preventing ischemia-reperfusion injury by acousto-mechanical local oxygen delivery

Yi Ju Ho*, Hui Ching Hsu, Bing Huan Wu, Yu Chun Lin, Lun De Liao, Chih Kuang Yeh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Ischemia-reperfusion (I/R) injury is a pathological process that causes vascular damage and dysfunction which increases recurrence and/or mortality in myocardial infarction, ischemic stroke, and organ transplantation. We hypothesized that ultrasound-stimulated oxygen-loaded microbubble (O2-MB) cavitation would enhance mechanical force on endothelium and simultaneously release oxygen locally at the targeted vessels. This cooperation between biomechanical and biochemical stimuli might modulate endothelial metabolism, providing a potential clinical approach to the prevention of I/R injury. Murine hindlimb and cardiac I/R models were used to demonstrate the feasibility of injury prevention by O2-MB cavitation. Increased mechanical force on endothelium induced eNOS-activated vasodilation and angiogenesis to prevent re-occlusion at the I/R vessels. Local oxygen therapy increased endothelial oxygenation that inhibited HIF-1α expression, increased ATP generation, and activated cyclin D1 for cell repair. Moreover, a decrease in interstitial H2O2 level reduced the expression of caspase3, NFκB, TNFα, and IL6, thus ameliorating inflammatory responses. O2-MB cavitation showed efficacy in maintaining cardiac function and preventing myocardial fibrosis after I/R. Finally, we present a potential pathway for the modulation of endothelial metabolism by O2-MB cavitation in relation to I/R injury, wound healing, and vascular bioeffects.

Original languageEnglish
Pages (from-to)481-492
Number of pages12
JournalJournal of Controlled Release
Volume356
DOIs
StatePublished - Apr 2023

Keywords

  • Ischemia-reperfusion injury
  • Mechanical force
  • Oxygen microbubble
  • Oxygen therapy
  • Ultrasound

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