scholarly journals Pre-ischaemic mitochondrial substrate constraint by inhibition of malate-aspartate shuttle preserves mitochondrial function after ischaemia-reperfusion

2017 ◽  
Vol 595 (12) ◽  
pp. 3765-3780 ◽  
Author(s):  
Nichlas Riise Jespersen ◽  
Takashi Yokota ◽  
Nicolaj Brejnholt Støttrup ◽  
Andreas Bergdahl ◽  
Kim Bolther Paelestik ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Ischaemia Reperfusion ◽  
Malate Aspartate Shuttle ◽  
Substrate Constraint

scholarly journals Acetylcholinesterase inhibitor protects against cardiac ischaemia/reperfusion injury via enhancing mitophagy and rebalancing mitochondrial dynamics

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Khuanjing ◽  
S Palee ◽  
S.C Chattipakorn ◽  
N Chattipakorn
Keyword(s):  
Infarct Size ◽  
Mitochondrial Function ◽  
Sham Group ◽  
Mitochondrial Dynamics ◽  
Vehicle Group ◽  
Lv Function ◽  
Funding Source ◽  
Ros Production ◽  
Ischaemia Reperfusion ◽  
Mitochondrial Ros

Abstract Background Ischaemic heart disease is the most common cause of death globally. Although reperfusion therapy is essential to restore myocardial blood flow, it can also damage heart tissues, this process is known as ischaemia/reperfusion (I/R) injury. Cardiac autonomic imbalance including sympathetic overactivity and diminished parasympathetic activity plays an important role in cardiac I/R injury, resulting in left ventricular (LV) dysfunction. Increased vagus nerve activity by an electrical stimulation from an implantable medical device has been shown to be cardioprotective in cardiac I/R injury. However, the role of pharmacological intervention that increases parasympathetic activity on the heart during I/R is not clear. Purpose We investigated the effects of a parasympathomimetic drug, donepezil, on the heart with I/R injury. We hypothesized that donepezil exerts cardioprotective effects in rats with cardiac I/R injury by attenuating the impairment of cardiac mitochondrial function, mitochondrial dynamics and mitophagy, resulting in improved LV function. Methods Forty male Wistar rats were randomly divided into sham and I/R groups. In I/R group, rats were subjected to acute cardiac I/R injury by ligating left anterior descending coronary artery (LAD) for 30 mins followed by reperfusion for 120 mins, while sham group had similar operation but did not have LAD ligation. Moreover, rats in the I/R group were randomly assigned to be treated with either saline (vehicle group) or donepezil 3 mg/kg by intravenous injection. In donepezil-treated rats, they were divided into 3 subgroups to receive the drug at one of the following time-points; before ischaemia, or during ischaemia, or at the onset of reperfusion. During I/R protocol, LV function was recorded. At the end of protocol, the heart was removed to determine infarct size, cardiac mitochondrial function, mitochondrial dynamics, and mitophagy. Results Rats with cardiac I/R injury showed increased infarct size when compared to sham group (Fig. 1A). Rats in all donepezil-treated groups showed reduction of infarct size compared to the vehicle group. This accounts for ∼63%, ∼47%, and ∼44% reduction for the treatment before ischaemia, during ischaemia and onset of reperfusion, respectively. In addition, all donepezil-treated rats had improved LV function by attenuating the reduction of LV ejection fraction (Fig. 1B). The reduction in cardiac mitochondrial ROS production (Fig. 1C), increased mitophagy as indicated by increased PINK-1 expression (Fig. 1D), and rebalancing mitochondrial dynamics were also found in all donepezil-treated rats. Conclusion Donepezil protects against cardiac I/R injury by reducing mitochondrial ROS production, enhancing mitophagy, and improving mitochondrial dynamics, leading to decreased infarct size and improved cardiac function. Figure 1. The effects of donepezil in cardiac I/R Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Thailand Research Fund grants TRF-Royal Golden Jubilee Program (TK and NC), RTA6180003 (SCC), RSA6180056 (SP); The NSTDA Research Chair grant from the National Science and Technology Development Agency Thailand (NC)

The roles of PKCδ and ϵ isoenzymes in the regulation of myocardial ischaemia/reperfusion injury

2007 ◽  
Vol 35 (5) ◽  
pp. 1040-1042 ◽  
Author(s):  
E.N. Churchill ◽  
D. Mochly-Rosen
Keyword(s):  
Reperfusion Injury ◽  
Mitochondrial Function ◽  
Cardiac Tissue ◽  
Heart Function ◽  
The Novel ◽  
Regulatory Pathway ◽  
Ischaemia Reperfusion Injury ◽  
Kinase C ◽  
Ischaemia Reperfusion ◽  
Pkc Protein Kinase C

Reperfusion of ischaemic cardiac tissue is associated with increased apoptosis and oncosis, resulting in diminished heart function. Short bouts of ischaemia before the prolonged ischaemic event (ischaemic preconditioning) protect the heart from injury mediated by reperfusion. The PKC (protein kinase C) family of serine/threonine kinases are involved in many different signalling processes. Two calcium-insensitive isoforms of the novel PKC subfamily, PKCδ and ϵ, play opposing roles in ischaemia/reperfusion injury. Activation of PKCδ during reperfusion induces cell death through the regulation of mitochondrial function and induction of apoptosis and oncosis. In contrast, activation of PKCϵ before ischaemia protects mitochondrial function and diminishes apoptosis and oncosis. How can two highly homologous PKC isoenzymes play such opposing roles through the regulation of mitochondrial function? This review will highlight what is known about PKCδ and ϵ function during ischaemia/reperfusion injury and will suggest a novel regulatory pathway which determines the fate of the cell following ischaemic stress.

scholarly journals Role of mitochondrial function in the protective effects of ischaemic postconditioning on ischaemia/reperfusion cerebral damage

2013 ◽  
Vol 41 (3) ◽  
pp. 618-627 ◽  
Author(s):  
Jian-min Liang ◽  
Hai-yang Xu ◽  
Xiao-jie Zhang ◽  
Xungeng Li ◽  
Hong-bo Zhang ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Protective Effects ◽  
Cerebral Damage ◽  
Ischaemia Reperfusion

Preserved cardiac mitochondrial function and reduced ischaemia/reperfusion injury afforded by chronic continuous hypoxia: Role of opioid receptors

2015 ◽  
Vol 42 (5) ◽  
pp. 496-501 ◽  
Author(s):  
Leonid N Maslov ◽  
Natalia V Naryzhnaya ◽  
Ekaterina S Prokudina ◽  
Frantisek Kolar ◽  
Alexander S Gorbunov ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Opioid Receptors ◽  
Mitochondrial Function ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion

Cardiopreventive effects of mitochondrial dynamics modulators in pre-diabetic rats subjected to cardiac ischaemia-reperfusion injury

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Maneechote ◽  
S Palee ◽  
T Jaiwongkam ◽  
S Kerdphoo ◽  
S.C Chattipakorn ◽  
...  
Keyword(s):  
Infarct Size ◽  
Mitochondrial Function ◽  
Chronic Treatment ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Diabetic Rats ◽  
Mitochondrial Fusion ◽  
Lv Function ◽  
Funding Source ◽  
Ischaemia Reperfusion

Abstract Background Chronic exposure to a high-fat diet (HFD) consumption causes alteration of cardiac mitochondrial dynamics and function, leading to the abnormal left ventricular (LV) function. Since excessive mitochondrial fission and reduced mitochondrial fusion are correlated with both obesity and myocardial ischaemia, targeting mitochondrial fission and fusion could be an effective cardioprotective strategy. We previously showed that acute inhibition of mitochondrial fission and promotion of mitochondrial fusion exerted cardioprotection in obese rats. However, the chronic treatment with mitochondrial fission inhibitor (Mdivi-1) and mitochondrial fusion promoter (M1) in pre-diabetic rats subjected to cardiac ischaemia-reperfusion (I/R) injury has never been investigated. Purpose We investigated the cardiopreventive effects of chronic Mdivi-1 and M1 treatment in pre-diabetic rats with cardiac I/R injury on infarct size, mitochondrial function, and LV contractility. Methods Wistar rats (n=32, male) were fed with HFD for 12 weeks, then randomly divided into: 1) HFV (Vehicle, 0.1% DMSO), 2) HFMdivi1 (Mdivi-1, 1.2 mg/kg), and 3) HFM1 (M1, 2 mg/kg) with intraperitoneal injection. After 2 weeks of drugs administration, all rats underwent 30 min of left anterior descending coronary artery occlusion followed by reperfusion for 120 min. LV function was monitored throughout the experiment. At the end, the heart was removed to determine infarct size and mitochondrial function. Results Chronic treatment with Mdivi-1 and M1 similarly showed a decrease in mitochondrial reactive oxygen species and infarct size, leading to an improvement in LV function in HFD rats, as indicated by increased ejection fraction, when compared to HFV rats (Figure). Conclusion Mitochondrial fission inhibitor and fusion promoter exerted similar efficacy in protecting pre-diabetic rat hearts against cardiac I/R injury through attenuating mitochondrial dysfunction, reducing infarct size and increasing LV contractility. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The National Science and Technology Development Agency Thailand

Ischaemia-reperfusion induced alterations of mitochondrial function in hypertrophied rat heart

1996 ◽  
Vol 156 (1) ◽  
pp. 51-60 ◽  
Author(s):  
S. B. LEICHTWEIS ◽  
C. LEEUWENBURGH ◽  
R. CHANDWANEY ◽  
D. J. PARMELEE ◽  
L. L. JI
Keyword(s):  
Mitochondrial Function ◽  
Rat Heart ◽  
Ischaemia Reperfusion

Rigorous swim training impairs mitochondrial function in post-ischaemic rat heart

1997 ◽  
Vol 160 (1) ◽  
pp. 139-148
Author(s):  
S.B. LEICHTWEIS ◽  
C. LEEUWENBURGH ◽  
D. J. PARMELEE ◽  
R. FIEBIG ◽  
L. L. JI
Keyword(s):  
Mitochondrial Function ◽  
Rat Heart
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