Abstract
Pharmacologic cardiac conditioning increases the intrinsic resistance against ischemia and reperfusion (I/R) injury. The cardiac conditioning response is mediated via complex signaling networks. These networks have been an intriguing research field for decades, largely advancing our knowledge on cardiac signaling beyond the conditioning response. The centerpieces of this system are the mitochondria, a dynamic organelle, almost acting as a cell within the cell. Mitochondria comprise a plethora of functions at the crossroads of cell death or survival. These include the maintenance of aerobic ATP production and redox signaling, closely entwined with mitochondrial calcium handling and mitochondrial permeability transition. Moreover, mitochondria host pathways of programmed cell death impact the inflammatory response and contain their own mechanisms of fusion and fission (division). These act as quality control mechanisms in cellular ageing, release of pro-apoptotic factors and mitophagy. Furthermore, recently identified mechanisms of mitochondrial regeneration can increase the capacity for oxidative phosphorylation, decrease oxidative stress and might help to beneficially impact myocardial remodeling, as well as invigorate the heart against subsequent ischemic insults. The current review highlights different pathways and unresolved questions surrounding mitochondria in myocardial I/R injury and pharmacological cardiac conditioning.
Highlights
Myocardial ischemic injury is composed of two different entities with distinct molecular mechanisms
Short periods of ischemia interspersed by reperfusion followed by a sustained ischemia limited the resulting infarct size to 25% compared to the control group [2]
Cardioprotective effects of volatile anesthetics have been known for three decades and cardiac protection is similar in magnitude to ischemic preconditioning [4]
Summary
Myocardial ischemic injury is composed of two different entities with distinct molecular mechanisms. Mitochondria comprise a plethora of functions at the crossroads of cell death or survival These include the maintenance of aerobic ATP production, redox signaling, calcium transport, and pathways of cell death. The resulting Na+ accumulation leads to reversed mode operation of the Na+ /Ca2+ ion exchanger, culminating in intracellular and mitochondrial Ca2+ overload [12,13] These mechanisms are exaggerated during the beginning of myocardial reperfusion due to damage to the plasma and sarcoplasmic membranes, rapid washout of lactate, restoration of intracellular pH, and mitochondrial respiratory chain dysfunction. While impairing mitochondrial bioenergetics, Ca2+ independent mechanisms might compensate these energy deficits during chronic overexpression of MCUB This could limit cell death during the later stages of I/R injury and heart failure development [17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
