scholarly journals Late Exercise Preconditioning Promotes Autophagy against Exhaustive Exercise-Induced Myocardial Injury through the Activation of the AMPK-mTOR-ULK1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Hong-Tao Liu ◽  
Shan-Shan Pan
Keyword(s):  
Myocardial Protection ◽  
Myocardial Injury ◽  
Troponin I ◽  
Picric Acid ◽  
Exhaustive Exercise ◽  
Class Iii ◽  
Hypoxic Injury ◽  
Exercise Preconditioning ◽  
Exercise Induced ◽  
The Relationship

Accumulating evidence shows that the AMPK-mTOR pathway modulates autophagy via coordinated phosphorylation of ULK1. The aim of the present study was to investigate the relationship between AMPK, mTOR, and ULK1 during late exercise preconditioning (LEP), and to explore whether LEP-induced myocardial protection is related to the autophagy. The exercise preconditioning (EP) protocol was as follows: rats were instructed to for run four repeated in duration of 10 minutes (including 10 minutes rest between each period) on a treadmill. Exhaustive exercise (EE) after LEP pretreatment and administration of wortmannin (an autophagy inhibitor that suppresses Class III PI3K-kinase (PI3KC3) activity) were added to test the protective effect. Cardiac troponin I (cTnI), and transmission electron microscopy (TEM), along with hematoxylin-basic fuchsin-picric acid (HBFP) staining, were used to evaluate the myocardial ischemic-hypoxic injury and protection. Western blot was used to analyze the relationship of autophagy-associated proteins. Exhaustive exercise caused severe myocardial ischemic-hypoxic injury, which led to an increase in cTnI levels, changes of ischemia–hypoxia, and cells ultrastructure. Compared with the EE group, LEP significantly suppressed exhaustive exercise-induced myocardial injury. However, wortmannin attenuated LEP-induced myocardial protection by inhibiting autophagy. Compared with the C group, AMPK was increased in the LEP, EE, and LEP+EE groups, but phosphorylation of AMPK at Thr172 was not significantly changed. Exercise did not have any effect on mTOR expression. Compared with the C group, ULK1 was increased and the ULK1ser757/ULK1 ratio was decreased in the LEP and LEP+EE groups. ULK1 was not significantly affected in the EE group, however, phosphorylation of ULK1 at Ser757 was remarkably decreased. To sum up, our results suggested that LEP promoted autophagy through the activation of AMPK-mTOR-ULK1 pathway, and that activated autophagy was partially involved in myocardial protection against EE-induced myocardial ischemic-hypoxic injury.

Nicorandil reduces myocardial injury and improves cardiac function in valve replacement surgery.

2019 ◽  
Vol 1 (4) ◽  
pp. 120-126
Author(s):  
Wael Elfeky ◽  
Mohamed Aboelnasr ◽  
Ayman Sallam ◽  
Wael Haseeb ◽  
Dalia R El-Afify
Keyword(s):  
Valve Replacement ◽  
Myocardial Protection ◽  
Myocardial Injury ◽  
Troponin I ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Replacement Surgery ◽  
Tnf Α ◽  
Valve Replacement Surgery

Background: Myocardial injury during cardiac surgery is associated with increased morbidity and mortality, and proper myocardial protection improves surgical outcomes. We aimed to study the role of preoperative nicorandil in myocardial protection during valve replacement surgery. Methods: The study included 40 patients who were randomized into two groups: control group, and nicorandil group. Preoperative, intraoperative, and postoperative data were collected. Creatine kinase- MB (CK-MB), troponin I, malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured 24-hours before surgery then 4, 12 and 48 hours after aortic cross-clamp removal. Results: Nicorandil significantly decreased MDA (p=0.005 and 0.036), TNF-α (p< 0.001), IL-6 (p<0.001 and 0.003) 4 and 12 hours following the removal of aortic clamp compared to the control group. Additionally, It significantly reduced CK-MB (p< 0.0001 and 0.0002) and troponin-I (p= 0.0002 and < 0.0001) 4 and 12 hours after the removal of the aortic clamp, respectively. However, there was no significant difference in MDA, TNF-α, IL-6, CK-MB, and troponin-I levels between the nicorandil and the control group after 48 hours following the removal of aortic clamping (p= 0.084; 0.64; 0.12; 0.12; 0.75; respectively). Conclusions: Nicorandil reduced myocardial injury significantly in valve replacement surgery. Nicorandil decreased CK-MB and troponin I and improved postoperative left ventricular ejection fraction.

scholarly journals Is cardiac troponin elevation following strenuous exercise clinically relevant in healthy subjects?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Orn ◽  
T.H Melberg ◽  
T Omland ◽  
O Skadberg ◽  
M.F Bjorkavoll-Bergseth ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Healthy Subjects ◽  
Myocardial Injury ◽  
Troponin I ◽  
University Hospital ◽  
Strenuous Exercise ◽  
Funding Source ◽  
Increased Risk ◽  
Exercise Induced

Abstract Background Exercise causes an increase in cardiac troponin (cTn) levels. Exercise-induced myocardial injury (cTn &gt; the 99th percentile) has been associated with adverse cardiovascular (CV) outcomes in older subjects with CV risk factors. The long-term clinical implications of exercise-induced cardiac troponin elevations in healthy individuals has not been determined. Purpose To assess the association between exercise-induced cardiac troponin increase above the 99th percentile and all-cause death, myocardial infarction, revascularization, sudden cardiac arrest, heart failure admission and stroke during 5-years follow-up in a large cohort of healthy recreational athletes. Methods 1002 healthy subjects that completed a 91-km bike race in 2014 were eligible. Follow-up data was available for 991 subjects (99%). High-sensitivity cardiac troponin I (cTnI) and T (cTnT) were obtained 24h prior to the race, and at 3h and 24h after the race in 2014. Results Median age was 46 (25th-75th percentile: 40–53) years at inclusion, and 776 (78%) were male. Race duration was 3.8 (3.4–4.3) hours. At 3-hours following the race 821 (82.8%) of subjects exceeded the sex-specific 99th percentile of the cTnI assay and 910 (91.8%) of the cTnT assay. At 24-hours following the race 168 (17%) of subjects exceeded the sex-specific 99th percentile of the cTnI assay and 263 (27%) of the cTnT assay. During 5 years of follow-up 12 subjects (1.2%) suffered a CV event. Exercise-induced cardiac troponin increase above the 99th percentile was not associated with increased risk of adverse CV events, neither at 3-hours nor at 24-hours following the race (Figure 1). This finding was further supported by no significant relationship between adverse CV events and cTnI or cTnT at any time-point, assessed as continuous variables. Conclusion Myocardial injury, defined as a cardiac troponin level above the 99th percentile, occurs frequently following strenuous exercise. In the present study, however, healthy subjects with cardiac troponin increase above the 99th percentile following strenuous exercise were not found to have an increased five-year risk of cardiovascular events. frequent occurrence following strenuous exercise. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Stavanger University Hospital, Abbott Diagnostics

P4425The exercise-induced troponin I elevation is highly correlated with power output during exercise in recreational cyclists with coronary atherosclerosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Bjorkavoll-Bergseth ◽  
O Kleiven ◽  
K M Aakre ◽  
T Wiktorski ◽  
C Erevik ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Coronary Atherosclerosis ◽  
Troponin I ◽  
Average Power ◽  
Strenuous Exercise ◽  
Significant Difference ◽  
Highly Correlated ◽  
Exercise Induced ◽  
The Relationship

Abstract Background Following strenuous exercise there is an increase cardiac Troponins (cTn) elevation considered being a physiological response. During prolonged strenuous physical activity, high work-loads may induce demand myocardial ischemia due to an oxygen demand/supply mismatch in susceptible subjects, causing an excessive cTn elevation. Purpose This study aimed to assess the relationship between exercise-induced cTnI elevation and direct measurement of work performed during prolonged strenuous exercise in subjects with and without atherosclerotic CAD. Methods Work during a 91 km mountain bike race was quantified by Stages™ power meters. Power (Watt) and heart rate data were stored in Garmin™ Forerunner 935 monitors. Coronary computed tomography angiography was performed after the race. Blood pressure was measured 4 times during the race. Blood samples (hs-cTnI from Abbot Diagnostics) were obtained one day prior to the race and at 3 and 24 h after the race. Data are presented as mean±SD or median (25th and 75th percentile). Results 40 subjects (10 women) were included in the final analysis. 15 Participants (4 women) had atherosclerosis, none had obstructive CAD. These participants were significantly older (55±8 years vs. 46±8 years p=0.007) and had higher training volumes (METS: 69 (64–102) hrs/week) compared with normal subjects (METS: 51 (33–88) hrs/week) (p=0.03). Baseline cTnI was higher (p=0.04) in the atherosclerotic group (4.5 (3.4–8.8) ng/L) compared with normals (2.6 (1.6–4.8) ng/L). There were no differences in baseline blood pressure, peak VO2 max, heart rate or BMI. There was no significant difference in race duration between normals (3.9 (3.5–4.5) hrs) and subjects with atherosclerosis (4.1 (3.6–4.5) hrs). During the race there were no differences in peak power or peak Watt/kg. cTnI increased after the race in all participants, but there were no differences between groups: 3h: atherosclerosis: 89 (27–131) ng/L vs. normal 77 (36–104) ng/L, 24h: atherosclerosis: 13 (6.3–23.7) ng/L vs. normal: 17 (12–37) ng/L. There were no significant difference between the groups in average power during the race: atherosclerosis: 167±50 Watt vs. 174 (±50) Watt or ratio: 2.0±0.49 Watt/kg vs 2.2±0.58 Watt/kg during the race. Maximal systolic and diastolic blood pressures during the race were higher (p=0.002) in the atherosclerotic group: SBP: 241±14 mmHg vs. 219±26 mmHg, DBP: 107±8 vs 95±8 mmHg. In atherosclerotic subjects cTnI both at 3h and 24 h were highly correlated (p<0.001) with Watt/kg ratio during the race in contrast to no correlations in the normal group (Figure). Conclusions Our findings suggest that the presence of coronary atherosclerosis, even in the absences of significant stenosis, alters the relationship between workload and the troponin response. This indicates different release kinetics in exercise-induced cTn in participants with and without CAD, with prolonged elevation in cTnI in CAD subjects exceeding the highest work-intensities. Acknowledgement/Funding Grant Western Norway Health service, Grant ConocoPhillips, Grant Simon Fougner Hartmanns Familyfund

scholarly journals Exercise Preconditioning Plays a Protective Role in Exhaustive Rats by Activating the PI3K-Akt Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jingjing Li ◽  
Peng Xu ◽  
Yang Wang ◽  
Zheng Ping ◽  
Xuebin Cao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Myocardial Injury ◽  
Akt Signaling ◽  
Exercise Group ◽  
Treadmill Running ◽  
Exhaustive Exercise ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Sprague Dawley ◽  
Exercise Preconditioning

Objective. To investigate whether exercise preconditioning (EP) protects the rat heart from exhaustive exercise- (EE-) induced injury by inducing the PI3K-Akt signaling pathway. Methods. 84 male Sprague-Dawley rats were randomly divided into 6 groups (n = 14 rats per group): control group (Con), exhaustive exercise group (EE), exercise preconditioning group (EP), exercise preconditioning + exhaustive exercise group (EP + EE), LY294002 (PI3K inhibitor) + exercise preconditioning + exhaustive exercise group (LY + EP + EE), and LY294002 group (LY). The Con and LY did not exercise. The remaining groups were subjected to treadmill running. The structure of myocardial tissue and serum biomarkers of myocardial injury were observed. Hemodynamic parameters were recorded with a pressure-volume catheter. TUNEL assay was used to detect the apoptosis of cardiac myocytes, and the level of mitochondrial membrane permeability transforming pore (mPTP) in myocardium was evaluated using ELISA. Pathway and apoptosis-related proteins in myocardium were assessed using western blotting. Results. Compared to the Con group, the EE group showed remarkable myocardial injury, such as cardiac dysfunction and myocardial apoptosis. Compared to the EE group, the injuries in the EP + EE group were improved. EP increased the PI3K-Akt signaling pathway and regulated Bcl-2 family to decrease the mPTP openness level. However, the cardioprotective effects of EP were attenuated when pretreated with the LY294002. Conclusions. EP protected the heart from EE-induced injury, and it may improve the cardiac function and reduce the cardiomyocyte apoptosis by activating the PI3K-Akt signaling pathway.

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