Intermittent hypoxia promotes fatty acid metabolism and improves myocardial energy homeostasis potentially via AMPKα1 pathway

Myocardial infarction (MI) disrupts cardiac energy metabolism and mitochondrial function. Intermittent hypoxia (IH) may confer cardioprotection. This study investigated whether IH improves myocardial fatty acid metabolism via the adenosine monophosphate-activated protein kinase alpha 1 (AMPKα1) pathway. To evaluate the effects of IH on myocardial energy metabolism, mitochondrial function, and cardiac performance in rats after myocardial infarction. Forty-two male Sprague-Dawley rats were randomly assigned to the sham operation, myocardial infarction with sedentary normoxia (MI-SED), or myocardial infarction with intermittent hypoxia (MI-IH) group. IH (fraction of inspired oxygen [FiO2] 13 % alternating with normoxia, 4 h/day, 5 days/week for 4 weeks) was initiated 1 week post-MI. Body weight, exercise capacity, echocardiography, serum biomarkers (cardiac troponin I [cTnI], creatine kinase [CK], creatine kinase–myocardial band [CK-MB], lactate dehydrogenase, free fatty acids [FFA]), myocardial fibrosis, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, citrate synthase (CS) activity, protein expression of AMPKα1, cluster of differentiation 36 (CD36), long-chain acyl-CoA dehydrogenase (LCAD), and acyl-CoA oxidase 1 (ACOX1) were measured. At 1 week, MI-IH rats showed reduced serum injury markers (cTnI: P = 0.03, CK: P = 0.011, CK-MB: P = 0.008) and FFA ( P < 0.001); increased MMP ( P = 0.003), ATP ( P = 0.041), and CS activity ( P = 0.049); and elevated expression levels of AMPKα1, CD36, LCAD, and ACOX1 compared with MI-SED rats. At 4 weeks, MI-IH rats exhibited greater body weight ( P <0.001), exercise capacity ( P < 0.001), and left ventricular ejection fraction (LVEF) (mean difference: 15.33 %; 95 % confidence interval [CI]: 11.21–19.44; P < 0.001); reduced myocardial fibrosis (mean difference: −11.43 %; 95 % CI: −14.69 to −8.17; P < 0.001); and improved mitochondrial number and ultrastructure, with sustained protein upregulation. IH intervention enhances fatty acid metabolism, improves mitochondrial tricarboxylic acid cycle efficiency, promotes ATP synthesis, preserves mitochondrial ultrastructure, reduces fibrosis, and improves cardiac function in MI rats, potentially through AMPKα1 pathway activation.