Background
Myocardial infarction (MI) is a major risk factor for the development of heart failure with reduce ejection fraction (HFrEF). While previous studies have focused on HFrEF, the cardiovascular effects of ketone bodies in acute MI are unclear. We examined the effects of oral ketone supplementation as a potential treatment strategy in a swine acute MI model.
Conclusions
Oral KE supplementation induced ketosis and enhanced myocardial βHB extraction in both healthy and infarcted hearts. Acute oral supplementation with KE favorably altered cardiac substrate uptake and utilization, improved cardiac ATP levels, and reduced cardiac inflammation following MI.
Methods
Farm pigs underwent percutaneous balloon occlusion of the LAD for 80 min followed by 72 h reperfusion period. Oral ketone ester or vehicle was administered during reperfusion and continued during the follow-up period.
Results
Oral KE supplementation induced ketonemia 2-3 mmol/l within 30 min after ingestion. KE increased ketone (βHB) extraction in healthy hearts without affecting glucose and fatty acid (FA) consumption. During reperfusion, the MI hearts consumed less FA with no change in glucose consumption, whereas hearts from MI-KE-fed animals consumed more βHB and FA, as well as improved myocardial ATP production. A significant elevation of infarct T2 values indicative of inflammation was found only in untreated MI group compared to sham. Concordantly, cardiac expression of inflammatory markers, oxidative stress, and apoptosis were reduced by KE. RNA-seq analysis identified differentially expressed genes related to mitochondrial energy metabolism and inflammation. Conclusions: Oral KE supplementation induced ketosis and enhanced myocardial βHB extraction in both healthy and infarcted hearts. Acute oral supplementation with KE favorably altered cardiac substrate uptake and utilization, improved cardiac ATP levels, and reduced cardiac inflammation following MI.