Frank W. Sellke, MD
Central Message
Hyperglycemia in acute MI is associated with reduced survival, but we do not know why. Pulsed ultrasound may possibly lessen infarct size in this setting but will need verification in clinical trials.
See Article page e297.
Diabetes 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. It may just be a marker of illness. Indeed, there are other studies that have not found an injurious effect of hyperglycemia in the setting of myocardial infarction, and there are some studies that find a reduction in infarct size in the setting of hyperglycemia3
related to increased expression of cell survival proteins. It is therefore clear that we really do not have a good handle on the effects of hyperglycemia on myocardial infarction, except that hyperglycemia is a marker of poor outcome in the setting of myocardial infarction.In this issue of the Journal, Charles and colleagues
4
report their examination of a novel method that potentially could reduce the hyperglycemia-induced exacerbation of myocardial ischemia reperfusion injury, pulsed ultrasound. In a previous study by this group, Gigliotti and colleagues5
found that acute hyperglycemia induced splenic leukocytes and that pulses ultrasound inhibited this effect. Gigliotti and colleagues5
concluded that there was a causal relationship between splenic leukocytes and infarct size, and that the pulsed ultrasound-induced reduction in infarction was mediated by an anti-inflammatory mechanism acting on the splenic leukocytes. In the current study, Charles and colleagues4
found that the application of pulsed ultrasound, either in the area of the spleen or in the neck, reduced infarct size by two-thirds. In mice that had undergone vagotomy, the benefit disappeared, and it was not evident in knockout mice for the acetylcholine receptor, suggesting that the effect is related to a cholinergic mechanism.This is an interesting and well-executed study, but there are several pieces of information that are missing. First, what is the role of splenic leukocytes in infarct size? The mechanisms of myocardial injury in the setting of ischemia-reperfusion include complement, oxygen-derived free radicals, protein denaturation, and many other mechanisms, including activation of leukocytes. There have been many trials attempting to reduce infarct size, but nearly all have had negative results. Second, the study was performed in mice, which are known to be different from larger animals and certainly from human patients. Third, the model was somewhat artificial, in that the ischemic period was 30 minutes, followed by a very brief period of reperfusion. Patients presenting with an acute myocardial infarction generally have had pain for a longer period. Another consideration is the utility of pulsed ultrasound in limiting infarct size in patients. I am personally skeptical that this will show any benefit in patients, but ultrasound is noninvasive and associated with little risk of injury, so why not give it a try. After all, there are other methods to reduce myocardial ischemia, such as external lower extremity compression, that probably work and are used in parts of Asia, and we certainly do not have all the answers there either.
References
- Relation of admission glucose levels, short- and long-term (20-year) mortality after acute myocardial infarction.Am J Cardiol. 2013; 112: 1306-1310
- Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity.Eur Heart J. 2005; 26: 650-661
- Is hyperglycemia bad for the heart during acute ischemia?.J Thorac Cardiovasc Surg. 2010; 140: 1345-1352
- Pulsed ultrasound attenuates the hyperglycemic exacerbation of myocardial ischemia-reperfusion injury.J Thorac Cardiovasc Surg. 2021; 161: e297-e306
- Ultrasound modulates the splenic neuroimmune axis in attenuating AKI.J Am Soc Nephrol. 2015; 26: 2470-2481
Article info
Publication history
Published online: October 31, 2019
Accepted:
October 18,
2019
Received in revised form:
October 18,
2019
Received:
October 18,
2019
Footnotes
Funding was provided by grants RO1 HL46716, P20 GM 103652, and RO1 HL128831.
Disclosures: Author has nothing to disclose with regard to commercial support.
Identification
Copyright
© 2019 by The American Association for Thoracic Surgery
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- Pulsed ultrasound attenuates the hyperglycemic exacerbation of myocardial ischemia–reperfusion injuryThe Journal of Thoracic and Cardiovascular SurgeryVol. 161Issue 4
- PreviewAcute 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.
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