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.
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.
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.
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.
Abbreviations and Acronyms:BUS (B-mode ultrasound), CAP (cholinergic anti-inflammatory pathway), GEJ (gastroesophageal junction), HG (hyperglycemia), IRI (ischemia–reperfusion injury), LCA (left coronary artery), MI (myocardial infarction), pUS (pulsed ultrasound), WT (wild-type)
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Published online: November 02, 2019
Accepted: October 17, 2019
Received in revised form: October 15, 2019
Received: May 6, 2019
This work was supported by National Heart, Lung, and Blood Institute Grants T32HL007849, UM1HL088925, and R01HL130082. The authors had full control of the design of the study, methods used, results, data analysis, and production of the written manuscript.
© 2019 Published by Elsevier Inc. on behalf of The American Association for Thoracic Surgery
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- Commentary: The new kid in town: Pulsed ultrasound to prevent ischemia–reperfusion injuryThe Journal of Thoracic and Cardiovascular SurgeryVol. 161Issue 4
- PreviewIschemia–reperfusion injury (IRI) is a major clinical problem in all fields of medicine, especially in cardiac surgery and cardiology. Major improvements in understanding the pathophysiology, the causes, and the consequences have been achieved over the last decades.1-3 Charles and colleagues4 from Irving Kron's group in Charlottesville are to be congratulated for drawing our attention to a new nonpharmacologic, noninvasive therapy option to reduce infarct size during acute myocardial infarction (MI).
- Commentary: Hyperglycemia during myocardial infarction: Can sound waves improve outcomes?The Journal of Thoracic and Cardiovascular SurgeryVol. 161Issue 4
- PreviewDiabetes is increasing not only in North America but across the world. It is well-known that diabetes is associated with an increased incidence of myocardial infarction and both cardiovascular and all-cause mortalities. In the setting of either ST-segment or non–ST segment myocardial infarction, poor glycemic control in patients with diabetes and stress hyperglycemia in patients without diabetes is associated with worse outcomes.1 It is not clear whether tight glycemic control during acute myocardial infarction improves outcome,2 however, or even whether hyperglycemia leads to increased ischemic injury or is truly a cause of the worse outcome.