Simulated microgravity increases myocardial susceptibility to ischemia-reperfusion injury via a deficiency of AMP-activated protein kinase.
Gravitation is an important factor in maintaining cardiac contractility. Our study investigated whether simulated microgravity increases myocardial susceptibility to ischemia-reperfusion (IR) injury. Using the Langendorff-perfused heart model with 300 beats/min pacing, 4-week tail suspension (SUS) and control (CON) male Sprague-Dawley rats (n = 10 rats/group) were subjected to 60 min of left anterior descending coronary artery (LAD) occlusion followed by 120 min of reperfusion. Left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), creatine kinase (CK) and lactate dehydrogenase (LDH) activity, and infarct size were assessed. Data demonstrated that there were significantly increased LVEDP, CK, LDH, and infarct size in SUS compared with CON (P < 0.05), accompanied by decreased LVESP (P < 0.05). Furthermore, TUNEL-positive cardiomyocytes were higher in SUS than that in CON (P < 0.01), and AMP-activated protein kinase (AMPK) phosphorylation and Bcl-2/Bax in SUS were less compared with CON (P < 0.05). Similarly, isolated hearts pre-treated with A-769662 exhibited better recovery of cardiac function, increased AMPK phosphorylation, and reduced necrosis and apoptosis. Furthermore, AMPKα protein showed a significant suppression in 4-week hindlimb unweighting rats. These results suggest that AMPK deficiency increases myocardial susceptibility to IR injury in rats subjected to simulated microgravity.
a Department of Aerospace Physiology, Fourth Military Medical University, Key Laboratory of Aerospace Medicine, Ministry of China, Xi'an, 710032, China.
Yuan-Ming
YM
Lu
a Department of Aerospace Physiology, Fourth Military Medical University, Key Laboratory of Aerospace Medicine, Ministry of China, Xi'an, 710032, China.
Bo
B
Jiao
b Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Jun
J
Lee
a Department of Aerospace Physiology, Fourth Military Medical University, Key Laboratory of Aerospace Medicine, Ministry of China, Xi'an, 710032, China.
Lin
L
Zhang
a Department of Aerospace Physiology, Fourth Military Medical University, Key Laboratory of Aerospace Medicine, Ministry of China, Xi'an, 710032, China.
Zhi-Bin
ZB
Yu
D055372:AMP-Activated Protein Kinases / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D001713:Biphenyl Compounds; D001835:Body Weight; D003402:Creatine Kinase / Q000378:metabolism; D006439:Hemodynamics; D019417:Hindlimb Suspension / Q000009:adverse effects; D000067268:Isolated Heart Preparation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009336:Necrosis / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011753:Pyrones / Q000494:pharmacology; D051381:Rats; D013876:Thiophenes / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D018474:Weightlessness Simulation
D001713:Biphenyl Compounds; D011753:Pyrones; D013876:Thiophenes; D007770:L-Lactate Dehydrogenase; D055372:AMP-Activated Protein Kinases; D003402:Creatine Kinase; C512408:4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile
AMPK; apoptose; apoptosis; infarctus du myocarde; ischemia–reperfusion; ischémie–reperfusion; microgravité simulée; myocardial infarct; simulated microgravity