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Page 2 of 8 Di Pumpo et al. Vessel Plus 2018;2:41 I http://dx.doi.org/10.20517/2574-1209.2018.38
[3]
In 1988, Warltier et al. demonstrated that the use of halothane or isoflurane improved left ventricular systolic
[4]
function. Subsequently, Cason et al. introduced the concept of cardiac pre-conditioning of the halogenates,
demonstrating that their administration before ischemia protects the myocardium from a subsequent lesion.

[5-9]
Since then, numerous studies both in vivo and in animals have demonstrated this phenomenon .

An international consensus conference included volatile agents among the few drugs that would decrease
[10]
perioperative mortality in cardiac surgery .

This mini-review aims to summarize the mechanism of action for cardioprotection of volatile anesthetics
and discuss the potential therapeutic implications.

MECHANISM OF ACTION FOR CARDIAC PROTECTION
Thanks to the use of animal models, we have been able to relate the ischemia/reperfusion injury with the
cardio-protection of volatile agents and establish a cause-effect relationship between the volatile anesthetic
and cardio-diagnostic points such as the reduction of death cellular, improvement of contractile function
[11]
and decrease in the incidence of arrhythmias .
A dose-dependent signal appears to be based on anesthetic cardiac preconditioning: the degree of protec-
tion depends on the concentration of the drug administered and the duration of the administration [12-15] .
[16]
Lange et al. has shown that there is a threshold for the preconditioning of desflurane which is included
between 0.5 and 1.0 minimum alveolar concentration. This threshold may decrease through the administra-
tion of desfuorane by intervals. As soon as the level of cardioprotection from desflurano is reached, it cannot
be further improved with desflurane increments.

All the volatile anesthetics that we use daily (desflurane, halothane, isoflurane and sevoflurane) produce car-
[16]
diac preconditioning because they have the same mechanism of action but different power .
Two types of preconditioning have been identified: one early, which lasts about 1 or 2 h, and one late, which
occurs after 24 h and lasts up to 72 h. Early and late preconditioning have many characteristics, but probably
[5]
involve different paths [Table 1] .

Myocardial reperfusion has two effects: decreases cardiac damage but activates apoptosis of the cells produc-
ing myocardial dysfunction, which is linked to mitochondrial dysfunction, in particular, at the opening of
mitochondrial permeability transition pores (mPTPs).

During reperfusion, volatile anesthetics avoid the opening of transitional pores of the mitochondrial perme-
ability. In this way the different mechanisms of apoptosis are inhibited [17,18] . In addition, anesthetics act on
the signaling pathways linked to adrenergic receptors and adenosine bradykinin, both involved in cardio-
[19]
protection .

Myocardial post-conditioning by the halogenates is due to various cellular mechanisms [16-18] : modulation of
L-type calcium channels, inhibition of the release of reactive oxygen species from the mitochondria to the
cytoplasm, mPTP closed, stimulation of G proteins coupled with β-adrenergic receptors.

Various pathways, including the activation of Gi (GiPCR) coupled Gi (inhibitors), phospholipase B and D
[5]
receptors, diacylglycerol and protein kinase C, are involved, activating KATP channels . KATP channels
are inhibited by intracellular ATP physiological concentrations and, when opened, produce a repolarizing
internal potassium stream. MitKATP channel antagonists may inhibit the cardioprotective function of des-