Mitochondrial targets for volatile anesthetics against cardiac ischemia-reperfusion injury

Agarwal, Bhawana; Stowe, David F.; Dash, Ranjan K.; Bošnjak, Željko J.; Camara, Amadou K.S.

doi:10.3389/fphys.2014.00341

Cited by 33 publications

(26 citation statements)

References 190 publications

(263 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the mechanism of APC and IPC share commonalities such as protein kinase C activation, 12,40 reactive oxygen species (ROS) generation, 14,41–43 and mitochondrial K + channels. 44–46 While the precise mechanism of APC is not well understood, evidence suggests that APC involves both altered mitochondrial function and K + channel activity (reviewed in 47 ).…”

Section: Discussionmentioning

confidence: 99%

Cardiac Slo2.1 Is Required for Volatile Anesthetic Stimulation of K+ Transport and Anesthetic Preconditioning

et al. 2016

View full text Add to dashboard Cite

Background Anesthetic preconditioning (APC) is a clinically important phenomenon in which volatile anesthetics (VAs) protect tissues such as heart against ischemic injury. The mechanism of APC is thought to involve K+ channels encoded by the Slo gene family, and the authors showed previously that slo-2 is required for APC in Caenorhabditis elegans. Thus, the authors hypothesized that a slo-2 ortholog may mediate APC-induced cardioprotection in mammals. Methods A perfused heart model of ischemia–reperfusion injury, a fluorescent assay for K+ flux, and mice lacking Slo2.1 (Slick), Slo2.2 (Slack), or both (double knockouts, Slo2.x dKO) were used to test whether these channels are required for APC-induced cardioprotection and for cardiomyocyte or mitochondrial K+ transport. Results In wild-type (WT) hearts, APC improved post-ischemia–reperfusion functional recovery (APC = 39.5 ± 3.7% of preischemic rate × pressure product vs. 20.3 ± 2.3% in controls, means ± SEM, P = 0.00051, unpaired two-tailed t test, n = 8) and lowered infarct size (APC = 29.0 ± 4.8% of LV area vs. 51.4 ± 4.5% in controls, P = 0.0043, n = 8). Protection by APC was absent in hearts from Slo2.1−/− mice (% recovery APC = 14.6 ± 2.6% vs. 16.5 ± 2.1% in controls, P = 0.569, n = 8 to 9, infarct APC = 52.2 ± 5.4% vs. 53.5 ± 4.7% in controls, P = 0.865, n = 8 to 9). APC protection was also absent in Slo2.x dKO hearts (% recovery APC = 11.0 ± 1.7% vs. 11.9 ± 2.2% in controls, P = 0.725, n = 8, infarct APC = 51.6 ± 4.4% vs. 50.5 ± 3.9% in controls, P = 0.855, n = 8). Meanwhile, Slo2.2−/− hearts responded similar to WT (% recovery APC = 41.9 ± 4.0% vs. 18.0 ± 2.5% in controls, P = 0.00016, n = 8, infarct APC = 25.2 ± 1.3% vs. 50.8 ± 3.3% in controls, P < 0.000005, n = 8). Furthermore, VA-stimulated K+ transport seen in cardiomyocytes or mitochondria from WT or Slo2.2−/− mice was absent in Slo2.1−/− or Slo2.x dKO. Conclusion Slick (Slo2.1) is required for both VA-stimulated K+ flux and for the APC-induced cardioprotection.

show abstract

Section: Discussionmentioning

confidence: 99%

Cardiac Slo2.1 Is Required for Volatile Anesthetic Stimulation of K+ Transport and Anesthetic Preconditioning

et al. 2016

View full text Add to dashboard Cite

show abstract

“…7–11 The ER and mitochondria are closely connected organelles within cells. 12, 13 The ER stress is involved in mitochondrial dysfunction in rat hearts.…”

mentioning

confidence: 99%

Metformin attenuates ER stress–induced mitochondrial dysfunction

Chen

Thompson

et al. 2017

Translational Research

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) stress, a disturbance of the ER function, contributes to cardiac injury. ER and mitochondria are closely connected organelles within cells. ER stress contributes to mitochondrial dysfunction, which is a key factor to increase cardiac injury. Metformin, a traditional anti-diabetic drug, decreases cardiac injury during ischemia-reperfusion. Metformin also inhibits ER stress in cultured cells. We hypothesized that metformin can attenuate the ER stress-induced mitochondrial dysfunction and subsequent cardiac injury. Thapsigargin (THAP, 3 mg/kg) was used to induce ER stress in C57BL/6 mice. Cell injury and mitochondrial function were evaluated in the mouse heart 48 hours after one-time THAP treatment. Metformin was dissolved in drinking water (0.5g/250 ml) and fed to mice for 7 days before THAP injection. Metformin feeding continued after THAP treatment. THAP treatment increased apoptosis in mouse myocardium compared to control. THAP also led to decreased oxidative phosphorylation in heart mitochondria oxidizing complex I substrates. THAP decreased the calcium retention capacity (CRC), indicating that ER stress sensitizes mitochondria to mitochondrial permeability transition pore opening. The cytosolic CHOP content was markedly increased in THAP-treated hearts compared to control, particularly in the nucleus. Metformin prevented the THAP-induced mitochondrial dysfunction and reduced CHOP content in cytosol and nucleus. Thus, metformin reduces cardiac injury during ER stress through the protection of cardiac mitochondria and attenuation of CHOP expression.

show abstract

“…Furthermore, anaesthetics are also being investigated as neuroprotective and cardioprotective agents, with researchers focussing on modulation of mitochondrial function as a key mode of action [108,109]. This suggests they could be activating mitohormetic mechanisms.…”

Section: Advanced Intelligence and Electro-magnetic Fields; A Role Fomentioning

confidence: 99%

The Hormesis of Thinking: A Deeper Quantum Thermodynamic Perspective?

Nunn¹,

Guy²,

Bell³

2017

Int J Neurorehabilitation Eng

View full text Add to dashboard Cite

We are able to read this because of quantum and thermodynamic principles that via an inorganic proton gradient, possibly generated 4.2 billion years ago, gave rise to a system that has an awareness of time and space by using energy to integrate information. Life can be described as a dissipative system driven by an energy gradient that uses information to positively reinforce its self-sustaining structure, which in turn increases its non-linear decisional capacity. Key in the evolution of life has been stress coupled to natural selection, which usually meant an increased demand for energy. As hormesis describes the adaptive response to stress, we propose that hormesis embraces not only the evolution of life, but that of intelligence itself, as natural selection would favour systems that enhances its efficiency. A component of the hormetic response in eukaryotes is the mitochondrion, which itself relies on quantum effects such as tunnelling. This suggests that quantum effects control the stability of individual cells as well as long-lived cellular networks. Hormesis, which can be anti-inflammatory, is therefore key in maintaining the functional stability of complex systems, including the brain. In contrast, a lack of classical hormetic factors, such as physical activity, plant polyphenols, or calorie restriction, will lead to accelerated cognitive decline, which is associated with increased inflammation. However, there may be another previously unidentified factor that could also be considered hormetic, and that is thinking itself. Here we propose that the process of "thinking", and managing complex movement, induces "stress" in the neuronal system and is therefore in itself part of maintaining cognitive health and reserve throughout life. In effect, the right amount of thinking and information processing can beneficially induce adaptation, and this itself could be explainable by quantum thermodynamics.

show abstract

Mitochondrial targets for volatile anesthetics against cardiac ischemia-reperfusion injury

Cited by 33 publications

References 190 publications

Cardiac Slo2.1 Is Required for Volatile Anesthetic Stimulation of K+ Transport and Anesthetic Preconditioning

Cardiac Slo2.1 Is Required for Volatile Anesthetic Stimulation of K+ Transport and Anesthetic Preconditioning

Metformin attenuates ER stress–induced mitochondrial dysfunction

The Hormesis of Thinking: A Deeper Quantum Thermodynamic Perspective?

Contact Info

Product

Resources

About