Pulsed ultrasound attenuates the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury

Eric J. Charles, Yikui Tian, Aimee Zhang, Di Wu, J. Hunter Mehaffey, Joseph C. Gigliotti, Alexander L. Klibanov, Irving L. Kron, Zequan Yang

Research output: Contribution to journalArticle

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Abstract

Objective: Acute hyperglycemia during myocardial infarction worsens outcomes in part by inflammatory mechanisms. Pulsed ultrasound has anti-inflammatory potential in bone healing and neuromodulation. We hypothesized that pulsed ultrasound would attenuate the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury via the cholinergic anti-inflammatory pathway. Methods: Acute hyperglycemia was induced in wild-type C57BL6 or acetylcholine-receptor knockout (α7nAChR-/-) mice by intraperitoneal injection of glucose. Pulsed ultrasound (frequency 7 MHz, bursting mechanical index 1.2, duration 1 second, repeated every 6 seconds for 2 minutes, 20-second total exposure) was performed at the spleen or neck after glucose injection. Separate mice underwent vagotomy before treatment. The left coronary artery was occluded for 20 minutes, followed by 60 minutes of reperfusion. The primary end point was infarct size in explanted hearts. Results: Splenic pulsed ultrasound significantly decreased infarct size in wild-type C57BL6 mice exposed to acute hyperglycemia and myocardial ischemia–reperfusion injury (5.2% ± 4.4% vs 16.9% ± 12.5% of risk region, P = .013). Knockout of α7nAChR abrogated the beneficial effect of splenic pulsed ultrasound (22.2% ± 12.1%, P = .79 vs control). Neck pulsed ultrasound attenuated the hyperglycemic exacerbation of myocardial infarct size (3.5% ± 4.8%, P = .004 vs control); however, the cardioprotective effect disappeared in mice that underwent vagotomy. Plasma acetylcholine, β2 adrenergic receptor, and phosphorylated Akt levels were increased after splenic pulsed ultrasound treatment. Conclusions: Pulsed ultrasound treatment of the spleen or neck attenuated the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury leading to a 3-fold decrease in infarct size. Pulsed ultrasound may provide cardioprotection via the cholinergic anti-inflammatory pathway and could be a promising new nonpharmacologic, noninvasive therapy to reduce infarct size during acute myocardial infarction and improve patient outcomes.

Original languageEnglish (US)
JournalJournal of Thoracic and Cardiovascular Surgery
DOIs
StateAccepted/In press - Jan 1 2019

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Wounds and Injuries
Hyperglycemia
Anti-Inflammatory Agents
Neck
Vagotomy
Myocardial Infarction
Cholinergic Agents
Spleen
Ultrasonic Waves
Glucose
Cholinergic Receptors
Therapeutics
Intraperitoneal Injections
Knockout Mice
Adrenergic Receptors
Acetylcholine
Reperfusion
Coronary Vessels
Bone and Bones
Injections

Keywords

  • cholinergic anti-inflammatory pathway
  • myocardial ischemia-reperfusion injury
  • pulsed ultrasound

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Pulsed ultrasound attenuates the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury. / Charles, Eric J.; Tian, Yikui; Zhang, Aimee; Wu, Di; Mehaffey, J. Hunter; Gigliotti, Joseph C.; Klibanov, Alexander L.; Kron, Irving L.; Yang, Zequan.

In: Journal of Thoracic and Cardiovascular Surgery, 01.01.2019.

Research output: Contribution to journalArticle

Charles, Eric J. ; Tian, Yikui ; Zhang, Aimee ; Wu, Di ; Mehaffey, J. Hunter ; Gigliotti, Joseph C. ; Klibanov, Alexander L. ; Kron, Irving L. ; Yang, Zequan. / Pulsed ultrasound attenuates the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury. In: Journal of Thoracic and Cardiovascular Surgery. 2019.
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abstract = "Objective: Acute hyperglycemia during myocardial infarction worsens outcomes in part by inflammatory mechanisms. Pulsed ultrasound has anti-inflammatory potential in bone healing and neuromodulation. We hypothesized that pulsed ultrasound would attenuate the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury via the cholinergic anti-inflammatory pathway. Methods: Acute hyperglycemia was induced in wild-type C57BL6 or acetylcholine-receptor knockout (α7nAChR-/-) mice by intraperitoneal injection of glucose. Pulsed ultrasound (frequency 7 MHz, bursting mechanical index 1.2, duration 1 second, repeated every 6 seconds for 2 minutes, 20-second total exposure) was performed at the spleen or neck after glucose injection. Separate mice underwent vagotomy before treatment. The left coronary artery was occluded for 20 minutes, followed by 60 minutes of reperfusion. The primary end point was infarct size in explanted hearts. Results: Splenic pulsed ultrasound significantly decreased infarct size in wild-type C57BL6 mice exposed to acute hyperglycemia and myocardial ischemia–reperfusion injury (5.2{\%} ± 4.4{\%} vs 16.9{\%} ± 12.5{\%} of risk region, P = .013). Knockout of α7nAChR abrogated the beneficial effect of splenic pulsed ultrasound (22.2{\%} ± 12.1{\%}, P = .79 vs control). Neck pulsed ultrasound attenuated the hyperglycemic exacerbation of myocardial infarct size (3.5{\%} ± 4.8{\%}, P = .004 vs control); however, the cardioprotective effect disappeared in mice that underwent vagotomy. Plasma acetylcholine, β2 adrenergic receptor, and phosphorylated Akt levels were increased after splenic pulsed ultrasound treatment. Conclusions: Pulsed ultrasound treatment of the spleen or neck attenuated the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury leading to a 3-fold decrease in infarct size. Pulsed ultrasound may provide cardioprotection via the cholinergic anti-inflammatory pathway and could be a promising new nonpharmacologic, noninvasive therapy to reduce infarct size during acute myocardial infarction and improve patient outcomes.",
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AU - Charles, Eric J.

AU - Tian, Yikui

AU - Zhang, Aimee

AU - Wu, Di

AU - Mehaffey, J. Hunter

AU - Gigliotti, Joseph C.

AU - Klibanov, Alexander L.

AU - Kron, Irving L.

AU - Yang, Zequan

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N2 - Objective: Acute hyperglycemia during myocardial infarction worsens outcomes in part by inflammatory mechanisms. Pulsed ultrasound has anti-inflammatory potential in bone healing and neuromodulation. We hypothesized that pulsed ultrasound would attenuate the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury via the cholinergic anti-inflammatory pathway. Methods: Acute hyperglycemia was induced in wild-type C57BL6 or acetylcholine-receptor knockout (α7nAChR-/-) mice by intraperitoneal injection of glucose. Pulsed ultrasound (frequency 7 MHz, bursting mechanical index 1.2, duration 1 second, repeated every 6 seconds for 2 minutes, 20-second total exposure) was performed at the spleen or neck after glucose injection. Separate mice underwent vagotomy before treatment. The left coronary artery was occluded for 20 minutes, followed by 60 minutes of reperfusion. The primary end point was infarct size in explanted hearts. Results: Splenic pulsed ultrasound significantly decreased infarct size in wild-type C57BL6 mice exposed to acute hyperglycemia and myocardial ischemia–reperfusion injury (5.2% ± 4.4% vs 16.9% ± 12.5% of risk region, P = .013). Knockout of α7nAChR abrogated the beneficial effect of splenic pulsed ultrasound (22.2% ± 12.1%, P = .79 vs control). Neck pulsed ultrasound attenuated the hyperglycemic exacerbation of myocardial infarct size (3.5% ± 4.8%, P = .004 vs control); however, the cardioprotective effect disappeared in mice that underwent vagotomy. Plasma acetylcholine, β2 adrenergic receptor, and phosphorylated Akt levels were increased after splenic pulsed ultrasound treatment. Conclusions: Pulsed ultrasound treatment of the spleen or neck attenuated the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury leading to a 3-fold decrease in infarct size. Pulsed ultrasound may provide cardioprotection via the cholinergic anti-inflammatory pathway and could be a promising new nonpharmacologic, noninvasive therapy to reduce infarct size during acute myocardial infarction and improve patient outcomes.

AB - Objective: Acute hyperglycemia during myocardial infarction worsens outcomes in part by inflammatory mechanisms. Pulsed ultrasound has anti-inflammatory potential in bone healing and neuromodulation. We hypothesized that pulsed ultrasound would attenuate the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury via the cholinergic anti-inflammatory pathway. Methods: Acute hyperglycemia was induced in wild-type C57BL6 or acetylcholine-receptor knockout (α7nAChR-/-) mice by intraperitoneal injection of glucose. Pulsed ultrasound (frequency 7 MHz, bursting mechanical index 1.2, duration 1 second, repeated every 6 seconds for 2 minutes, 20-second total exposure) was performed at the spleen or neck after glucose injection. Separate mice underwent vagotomy before treatment. The left coronary artery was occluded for 20 minutes, followed by 60 minutes of reperfusion. The primary end point was infarct size in explanted hearts. Results: Splenic pulsed ultrasound significantly decreased infarct size in wild-type C57BL6 mice exposed to acute hyperglycemia and myocardial ischemia–reperfusion injury (5.2% ± 4.4% vs 16.9% ± 12.5% of risk region, P = .013). Knockout of α7nAChR abrogated the beneficial effect of splenic pulsed ultrasound (22.2% ± 12.1%, P = .79 vs control). Neck pulsed ultrasound attenuated the hyperglycemic exacerbation of myocardial infarct size (3.5% ± 4.8%, P = .004 vs control); however, the cardioprotective effect disappeared in mice that underwent vagotomy. Plasma acetylcholine, β2 adrenergic receptor, and phosphorylated Akt levels were increased after splenic pulsed ultrasound treatment. Conclusions: Pulsed ultrasound treatment of the spleen or neck attenuated the hyperglycemic exacerbation of myocardial ischemia–reperfusion injury leading to a 3-fold decrease in infarct size. Pulsed ultrasound may provide cardioprotection via the cholinergic anti-inflammatory pathway and could be a promising new nonpharmacologic, noninvasive therapy to reduce infarct size during acute myocardial infarction and improve patient outcomes.

KW - cholinergic anti-inflammatory pathway

KW - myocardial ischemia-reperfusion injury

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