Cardiac protection by volatile anaesthetics

Tritapepe, Luigi; Landoni, Giovanni; Guarracino, Fabio; Pompei, F.; Crivellari, Martina; Maselli, Daniele; Luca, Monica De; Fochi, Oliviero; DʼAvolio, S.; Bignami, Elena; Calabrò, Maria Grazia; Zangrillo, Alberto

doi:10.1017/s0265021506001931

Cited by 84 publications

(12 citation statements)

References 19 publications

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“…Experimental data are supported by several clinical studies which showed less cardiac damage in patients receiving the volatile anesthetic desflurane compared to control patients [22]–[24]. Another study compared the effects of sevoflurane versus total intravenous anesthesia, in terms of postoperative cardiac troponin I release in patients undergoing noncardiac surgery.…”

Section: Discussionmentioning

confidence: 90%

Aromatase Inhibition Attenuates Desflurane-Induced Preconditioning against Acute Myocardial Infarction in Male Mouse Heart In Vivo

et al. 2012

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The volatile anesthetic desflurane (DES) effectively reduces cardiac infarct size following experimental ischemia/reperfusion injury in the mouse heart. We hypothesized that endogenous estrogens play a role as mediators of desflurane-induced preconditioning against myocardial infarction. In this study, we tested the hypothesis that desflurane effects local estrogen synthesis by modulating enzyme aromatase expression and activity in the mouse heart. Aromatase metabolizes testosterone to 17β- estradiol (E2) and thereby significantly contributes to local estrogen synthesis. We tested aromatase effects in acute myocardial infarction model in male mice. The animals were randomized and subjected to four groups which were pre-treated with the selective aromatase inhibitor anastrozole (A group) and DES alone (DES group) or in combination (A+DES group) for 15 minutes prior to surgical intervention whereas the control group received 0.9% NaCl (CON group). All animals were subjected to 45 minutes ischemia following 180 minutes reperfusion. Anastrozole blocked DES induced preconditioning and increased infarct size compared to DES alone (37.94±15.5% vs. 17.1±3.62%) without affecting area at risk and systemic hemodynamic parameters following ischemia/reperfusion. Protein localization studies revealed that aromatase was abundant in the murine cardiovascular system with the highest expression levels in endothelial and smooth muscle cells. Desflurane application at pharmacological concentrations efficiently upregulated aromatase expression in vivo and in vitro. We conclude that desflurane efficiently regulates aromatase expression and activity which might lead to increased local estrogen synthesis and thus preserve cellular integrity and reduce cardiac damage in an acute myocardial infarction model.

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Section: Discussionmentioning

confidence: 90%

Aromatase Inhibition Attenuates Desflurane-Induced Preconditioning against Acute Myocardial Infarction in Male Mouse Heart In Vivo

et al. 2012

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“…The study revealed less release of CK-MB and troponin, indicating attenuated cardiac injury in the isoflurane group. The cardioprotective potential of various volatile anesthetics, applied during surgery, measured by a reduction in biomarkers of cardiac injury, has been confirmed by many authors [11-13,19,20]. A meta-analysis performed in 2007 clearly suggested that sevoflurane or desflurane is able to reduce the incidence of myocardial infarction and postoperative mortality after cardiac surgery [21].…”

Section: Discussionmentioning

confidence: 96%

“…A meta-analysis performed in 2007 clearly suggested that sevoflurane or desflurane is able to reduce the incidence of myocardial infarction and postoperative mortality after cardiac surgery [21]. Some of these studies even showed benefits with regard to mechanical ventilation and/or length of hospital stay [12,13]. Different windows of pharmacologic protection with early and late pharmacologic preconditioning by the use of volatile anesthetics have been described in the literature, both probably involving different signaling pathways, which are still not understood in detail.…”

Section: Discussionmentioning

confidence: 99%

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Late pharmacologic conditioning with volatile anesthetics after cardiac surgery

Steurer

Baulig

et al. 2012

Crit Care

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IntroductionThe aim of this randomized controlled trial was to investigate whether volatile anesthetics used for postoperative sedation have any beneficial effects on myocardial injury in cardiac surgery patients after on-pump valve replacement.MethodsAnesthesia was performed with propofol. After arrival in the intensive care unit (ICU), 117 patients were randomized to be sedated for at least 4 hours with either propofol or sevoflurane. Sevoflurane was administered by using the anesthetic-conserving device. Troponin T, creatine kinase, creatine kinase from heart muscle tissue, myoglobin, and oxygenation index were determined on arrival at the ICU, 4 hours after sedation, and in the morning of the first postoperative day (POD1). Primary end points were cardiac injury markers on POD1. As secondary end points oxygenation, postoperative pulmonary complications, and ICU and hospital stay were documented.ResultsFifty-six patients were analyzed in the propofol arm, and 46 patients in the sevoflurane arm. Treatment groups were comparable with regard to patient demographics and intraoperative characteristics. Concentration of troponin T as the most sensitive marker for myocardial injury at POD1 was significantly lower in the sevoflurane group compared with the propofol group (unadjusted difference, -0.4; 95% CI, -0.7 to -0.1; P < 0.01; adjusted difference, -0.2; 95% CI, -0.4 to -0.02; P = 0.03, respectively).ConclusionsThe data presented in this investigation indicate that late postconditioning with the volatile anesthetic sevoflurane might mediate cardiac protection, even with a late, brief, and low-dose application.Trial registrationClinicalTrials.gov: NCT00924222.

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“…Clinical trials comparing the use of these anesthetics to intravenous anesthetics prior to coronary artery bypass grafting (CABG) showed statistically significant reductions in peak troponin I levels, need for postoperative inotropic support, and need for length of stay exceeding seven days 161–164 . In one study, a volatile anesthetic reduced one-year mortality 165 .…”

Section: Clinical Applications Of Pkc Regulatorsmentioning

confidence: 99%

Protein kinase C, an elusive therapeutic target?

Mochly‐Rosen

Das

Grimes

2012

Nat Rev Drug Discov

474

493

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Preface Protein kinase C (PKC) has been a tantalizing target for drug discovery ever since it was first identified as the receptor for the tumor promoter phorbol ester in 19821. Although initial therapeutic efforts focused on cancer, additional diseases, including diabetic complications, heart failure, myocardial infarction, pain and bipolar disease were targeted as researchers developed a better understanding of the roles that PKC’s eight conventional and novel isozymes play in health and disease. Unfortunately, both academic and pharmaceutical efforts have yet to result in the approval of a single new drug that specifically targets PKC. Why does PKC remain an elusive drug target? This review will provide a short account of some of the efforts, challenges and opportunities in developing PKC modulators to address unmet clinical needs.

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Cardiac protection by volatile anaesthetics

Abstract: Myocardial damage measured by cardiac troponin release could be reduced by volatile anaesthetics in coronary artery bypass surgery.

Cited by 84 publications

References 19 publications

Aromatase Inhibition Attenuates Desflurane-Induced Preconditioning against Acute Myocardial Infarction in Male Mouse Heart In Vivo

Aromatase Inhibition Attenuates Desflurane-Induced Preconditioning against Acute Myocardial Infarction in Male Mouse Heart In Vivo

Late pharmacologic conditioning with volatile anesthetics after cardiac surgery

Protein kinase C, an elusive therapeutic target?

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