Beneficial Effects of Halogenated Anesthetics in Cardiomyocytes: The Role of Mitochondria.

In the last few years, the use of anesthetic drugs has been related to effects other than those initially related to their fundamental effect, hypnosis. Halogenated anesthetics, mainly sevoflurane, have been used as a therapeutic tool in patients undergoing cardiac surgery, thanks to the beneficial effect of the cardiac protection they generate. This effect has been described in several research studies. The mechanism by which they produce this effect has been associated with the effects generated by anesthetic preconditioning and postconditioning. The mechanisms by which these effects are induced are directly related to the modulation of oxidative stress and the cellular damage generated by the ischemia/reperfusion procedure through the overexpression of different enzymes, most of them included in the Reperfusion Injury Salvage Kinase (RISK) and the Survivor Activating Factor Enhancement (SAFE) pathways. Mitochondria is the final target of the different routes of pre- and post-anesthetic conditioning, and it is preserved from the damage generated in moments of lack of oxygen and after the recovery of the normal oxygen concentration. The final consequence of this effect has been related to better cardiac function in this type of patient, with less myocardial damage, less need for inotropic drugs to achieve normal myocardial function, and a shorter hospital stay in intensive care units. The mechanisms through which mitochondrial homeostasis is maintained and its relationship with the clinical effect are the basis of our review. From a translational perspective, we provide information regarding mitochondrial physiology and physiopathology in cardiac failure and the role of halogenated anesthetics in modulating oxidative stress and inducing myocardial conditioning.

Comparative Study of the Efficacy of EHO-85, a Hydrogel Containing Olive Tree (Olea europaea) Leaf Extract, in Skin Wound Healing.

Olive tree (Olea europaea) leaf extract (OELE) has important antioxidant and anti-inflammatory properties, supporting its use in human clinical practice. We recently designed an amorphous hydrogel called EHO-85 (EHO indicates olive leaf extract in Spanish) containing OELE for skin ulcer treatments. Yet, its effectiveness has not been previously compared with other products used in routine clinical practice. This is necessary to evaluate its potential translation to the human clinic. Thus, in this study, the effect of EHO-85 on healing was evaluated in comparison with treatments containing Indian/Asiatic pennywort (Centella asiatica), hyaluronic acid, or dexpanthenol in a rat model. The speed of wound closure and histological parameters after seven and 14 days were analyzed. All treatments accelerated wound closure, but there were differences between them. Dexpanthenol after seven days produced the highest epithelialization and the lowest inflammation and vascularization. EHO-85 also promoted epithelialization and reduced vascularization. After 14 days, wounds treated with EHO-85 showed less inflammation and higher levels of collagen in the extracellular matrix. This indicates a higher degree of maturity in the regenerated tissue. In conclusion, the effect of EHO-85 on healing was equal to or superior to that of other treatments routinely used in human clinical practice. Therefore, these results, together with previous data on the effects of this hydrogel on ulcer healing in humans, indicate that EHO-85 is a suitable, low-cost, and efficient therapeutic option for wound healing.

Heart Failure after Cardiac Surgery: The Role of Halogenated Agents, Myocardial Conditioning and Oxidative Stress.

Heart disease requires a surgical approach sometimes. Cardiac-surgery patients develop heart failure associated with ischemia induced during extracorporeal circulation. This complication could be decreased with anesthetic drugs. The cardioprotective effects of halogenated agents are based on pre- and postconditioning (sevoflurane, desflurane, or isoflurane) compared to intravenous hypnotics (propofol). We tried to put light on the shadows walking through the line of the halogenated anesthetic drugs' effects in several enzymatic routes and oxidative stress, waiting for the final results of the ACDHUVV-16 clinical trial regarding the genetic modulation of this kind of drugs.

Identification of miRNAs as Biomarkers of Cardiac Protection in Non-Genetically Modified Primary Human Cardiomyocytes Exposed to Halogenated Hypnotics in an In Vitro Model of Transfection and Ischemia/Reperfusion: A New Model in Translational Anesthesia.

BACKGROUND: Many clinical studies have identified some circulating micro-RNAs (miRNAs) as potential biomarkers with regard to the cardioprotective effects of halogenated agents administered perioperatively during myocardial conditioning procedures. However, there is a major methodological difficulty in identifying these potential miRNA targets in cardiac cells. METHODS: We developed an in vitro protocol to analyze the differential expression of target miRNAs at the intracellular level in non-genetically modified primary human cardiomyocytes (HCMs) through their exposure to different hypnotic compounds (i.e., halogenated versus non-halogenated). For this purpose, we performed a validated in vitro model of "ischemia and reperfusion" with the transfection of specific miRNA mimics (MIMICs) designed to simulate naturally occurring mature miRNAs as a functional study. Afterwards, next-generation sequencing (NGS) was used to identify and quantify miRNAs and elucidate their function. The differences in miRNA expression between HCMs exposed to different hypnotic drugs, along with the prediction of functional miRNA targets, were assessed using a meticulous in-house bioinformatics pipeline in order to derive diagnostic biomarkers and possible therapeutic targets. CONCLUSION: In brief, this methodological procedure was designed to investigate whether the cardioprotective effects of halogenated agents are a phenomenon mediated by either the activation or the suppression of miRNAs targeted by halogenated anesthetics.