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Background: Anesthetic preconditioning (AP) is known to mimic ischemic preconditioning. The purpose of this study was to investigate the effects of an interrupted sevoflurane administration protocol on myocardial ischemia/reperfusion (I/R) injury. Methods: Male Wistar rats (n = 60) were ventilated for 30 min with room air (control group, CG) or with a mixture of air and sevoflurane (1 minimum alveolar concentration—MAC) in 5-min cycles, alternating with 5-min wash-out periods (preconditioned groups). Cytokines implicated in the AP response were measured. An (I/R) lesion was produced immediately after the sham intervention (CG) and preconditioning protocol (early AP group, EAPG) or 24 h after the intervention (late AP group, LAPG). The area of fibrosis, the degree of apoptosis and the number of c-kit+ cells was estimated for each group. Results: Cytokine levels were increased post AP. The area of fibrosis decreased in both EAPG and LAPG compared to the CG (p < 0.0001). When compared to the CG, the degree of apoptosis was reduced in both LAPG (p = 0.006) and EAPG (p = 0.007) and the number of c-kit+ cells was the greatest for the LAPG (p < 0.0001). Conclusions: Sevoflurane preconditioning, using an interrupted anesthesia protocol, is efficient in myocardial protection and could be beneficial to reduce perioperative or periprocedural ischemia in patients with increased cardiovascular risk. [ABSTRACT FROM AUTHOR]

Comparative studies on the efficacy and safety of Inhalation Anesthesia (IA) and Total IntraVenous Anesthesia (TIVA) have been performed for many years, and the results were various.The aim of this study was to evaluate new data on the clinical efficacy of anesthetic preconditioning, the difference between inhalation and intravenous anesthesia on cardiac protection and clinically relevant outcomes in cancer surgery.Materials and methods. We carried out a systematic review and meta-analysis on searches and analysis of the literature over the past five years in accordance to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Results. Out of the 759 articles which were initially identified, we selected 3 studies regarding the clinical significance of anesthetic cardioprotection and 10 studies comparing IA and TIVA in patients undergoing surgery for malignant diseases.Two meta-analyses and one multi-regional clinical trial (MRCT) suggest that further studies of the effectiveness of anesthetic cardioprotection is futile.A meta-analysis of 9 retrospective cohort studies and 1 MRCT showed a detrimental effect of IA on 3-year survival in surgical oncology (Hazard Ratio (HR): 1.73 (1.36; 1.96) Heterogeneity: Q = 8.336, df = 3, I2; f2= 64.01, overall effect analysis: Z = 2.386 (P

The second part of the overview presents and analyzes the current data on the methods of adjuvant pharmacological cardioprotection and possibilities of optimizing the anesthetic support and perioperative monitoring in high cardiac risk patients. Amendments made in international guidelines for the last 2–3 years on the basis of conclusive studies and meta-analyses have been examined. Cardioprotection mechanisms and information about its implementation in real clinical practice have been analysed. It has been shown that by no means all drugs under discussion can be widely used for prophytlactic purposes. Contemporary evidencebased recommendations concerning the optimization of anesthetic support and perioperative monitoring are given. A conclusion has been made that practical implementation of a comprehensive strategy aimed at reduction of the risk of cardiac complications might ensure decrease of both the incidence of severe cardiac complications and mortality due to them.

The article describes the main tendencies in anesthesiology, which have undergone the greatest changes in the last decade, according to the author. The article speculates on the choice of tactics and the qualitative components of peri-operative infusion therapy. The author gives an assessment of the current stage of studying the phenomenon of anesthetic preconditioning and acute heart failure management. And, finally, the challenges and achievements of the evidence-based medicine in anesthesiology are analyzed.

Myocardial ischemia/reperfusion (I/R) injury is a frequent perioperative threat, with numerous strategies developed to limit and/or prevent it. One interesting axis of research is the anesthetic preconditioning (APc) agent's hypothesis (such as sevoflurane, SEV). However, APc's mode of action is still poorly understood and volatile anesthetics used as preconditioning agents are often not well suited in clinical practice. Here, in vitro using H9C2 cells lines (in myeloblast state or differentiated toward cardiomyocytes) and in vivo in mice, we identified that SEV‐induced APc is mediated by a mild induction of reactive oxygen species (ROS) that activates Akt and induces the expression of the anti‐apoptotic protein B‐cell lymphoma‐extra large (Bcl‐xL), therefore protecting cardiomyocytes from I/R‐induced death. Furthermore, we extended these results to human cardiomyocytes (derived from induced pluripotent stem ‐ IPS ‐ cells). Importantly, we demonstrated that this protective signaling pathway induced by SEV could be stimulated using the antidiabetic agent metformin (MET), suggesting the preconditioning properties of MET. Altogether, our study identified a signaling pathway allowing APc of cardiac injuries as well as a rational for the use of MET as a pharmacological preconditioning agent to prevent I/R injuries. [ABSTRACT FROM AUTHOR]

This study was designed to use real-time imaging to test the hypothesis that delayed cardiac protection induced by volatile anesthetics inhibits apoptosis. Rats were divided into two groups. One group was exposed to 120 min of 33 % O2 [control group (CON group)] and the other group was exposed to 2.5 % sevoflurane in 33 % O2 for 120 min [sevoflurane group (SEVO group)]. Both groups were allowed to return to their cages for 24 h. After 24 h recovery, all rats underwent 30 min myocardial ischemia by occluding coronary artery followed by 2 h of reperfusion. After reperfusion, technetium-99m-labeled annexin-V was administered intravenously to identify apoptosis. Left ventricular samples were obtained to measure infarct size and radionuclide imaging and caspase-3. Radionuclide imaging indicated that apoptosis was reduced in SEVO group (0.78 % ± 0.82) when compared with the CON group (1.15 % ± 0.61), and the infarct size was also decreased in the SEVO group (40 % ± 7). The transferase dUTP nick end labeling (TUNEL)-positive cardiomyocytes in the SEVO group (16 % ± 6) were significantly decreased in the peri-infarct zone when compared with the CON group (28 % ± 4). After reperfusion, caspase-3 expression was significantly blunted in the SEVO group than in CON group (50 % ± 11 vs. 68 % ± 10, p < 0.05). This study used technetium-99m-labeled annexin-V of real-time imaging to detect cardiomyocyte apoptosis and the results were confirmed by the TUNEL assay and caspase-3 expression. We concluded that delayed volatile anesthetic preconditioning (APC) protects against I/R in vivo. The method of technetium-99m-labeled annexin-V of real-time imaging can be used to detect cardiomyocyte apoptosis in delayed APC during ischemia/reperfusion.

Vagus nerve activation may have important therapeutic significance for myocardial ischemia-reperfusion (IR) injury. Nitric oxide (NO) plays a vital role in the cardioprotective effects of anesthetic preconditioning (APC). Moreover, acetylcholine (ACh) prevents cardiomyocyte damage by activating AMP-activated protein kinase (AMPK) and increasing the phosphorylation of Ca2+/calmodulin-dependent protein kinase β (CaMKKβ). The aim of the present study was to determine whether APC could protect heart function by antagonizing IR damage via the cholinergic system. It was hypothesized that the NO synthase (NOS)/CaMKKβ/AMPK pathway might be involved in the cardioprotective effects induced by cholinergic receptor activation. Isolated rat hearts were subjected to ischemia for 30 min followed by 120 min of reperfusion. Volatile anesthetic sevoflurane (3.5%) was administered for 15 min before ischemia, then rinsed for 15 min. The muscarinic acetylcholine receptor (mAChR) antagonist atropine (ATR; 100 nM) and the nicotinic acetylcholine receptor (nAChR) antagonist hexamethonium (HEM; 50 μM) were administered 10 min before APC. Both mAChR and nAChR were involved in APC-induced cardioprotection. ATR and HEM treatment both abolished the protective effects of APC on IR damage in isolated hearts, demonstrating the importance of cholinergic receptors in the protection mechanism of APC. The present study thus suggests that APC plays a cardioprotective role, in part, by regulating neurohumoral pathways. In addition, there may be functional coupling between the two cholinergic receptors, and the NOS and CaMKKβ/AMPK pathways may play roles in shared pathways that mediate the cardioprotective effects of APC. These findings may provide insight into potential new mechanisms of APC-induced cardioprotection against IR injury. [ABSTRACT FROM AUTHOR]

Preconditioning, a milestone concept in the cardiovascular sciences introduced 32 years back by Murry. This concept opened a new era in the field of organ protection. To start with extensive studies done on ischemic preconditioning for myocardial protection, ischemic preconditioning is an endogenous science of cellular kinetics. Several components in signal transduction cascade have been identified but still some mechanisms not yet revealed. Anesthetic preconditioning also contributed a lot for myocardial protection and concreted the concept of preconditioning. We, with an inquisitive brain meticulously persuing newer methods of cardioprotection. Remote ischemic preconditioning (RIPC) is a brilliant example of it. RIPC can be future of cardioprotection, clinical trials and studies proved the benefits but yet to conclude the superiority of RIPC over myocardial ischemic cardioprotection. This review is an attempt to reveal this extraordinary concept with its basic cellular kinetics, methods, and recent trends.

Background: Anesthetic preconditioning (AP) is known to mimic ischemic preconditioning. The purpose of this study was to investigate the effects of an interrupted sevoflurane administration protocol on myocardial ischemia/reperfusion (I/R) injury. Methods: Male Wistar rats (n = 60) were ventilated for 30 min with room air (control group, CG) or with a mixture of air and sevoflurane (1 minimum alveolar concentration—MAC) in 5-min cycles, alternating with 5-min wash-out periods (preconditioned groups). Cytokines implicated in the AP response were measured. An (I/R) lesion was produced immediately after the sham intervention (CG) and preconditioning protocol (early AP group, EAPG) or 24 h after the intervention (late AP group, LAPG). The area of fibrosis, the degree of apoptosis and the number of c-kit+ cells was estimated for each group. Results: Cytokine levels were increased post AP. The area of fibrosis decreased in both EAPG and LAPG compared to the CG (p < 0.0001). When compared to the CG, the degree of apoptosis was reduced in both LAPG (p = 0.006) and EAPG (p = 0.007) and the number of c-kit+ cells was the greatest for the LAPG (p < 0.0001). Conclusions: Sevoflurane preconditioning, using an interrupted anesthesia protocol, is efficient in myocardial protection and could be beneficial to reduce perioperative or periprocedural ischemia in patients with increased cardiovascular risk.

The problem of myocardial protection in cardiac surgery is a challenge due to an increased number of interventions and severity of their complications related to the patient's status, pathophysiology of the artificial circulation and the used techniques for replacement of vital functions. Oxidative stress and formation of active oxygen species, as a consequence of the above mentioned processes, may result in systemic injury, such as acute heart failure, central nervous system dysfunction and acute renal injury. Short ischemic episodes before prolonged hypoxia with subsequent reperfusion can decrease cardiomyocyte injury. This phenomenon has been referred to as ischemic preconditioning. A similar effect is caused by inhalation anesthetics. Experimental and clinical data on anesthetic preconditioning suggest that inhalation anesthesia with halogen-containing agents may be used as a method to protect the myocardium from damage by active oxygen species produced during the periods of oxidative stress in cardiac surgery. Studies analyzed in this review have shown benefits of inhalation anesthetics, compared to total intravenous anesthesia, such as effective cardiac protection and, what is most important, in potential reduction of mortality after coronary bypass grafting. The level of evidence for the effects of anesthetic preconditioning on long-term mortality in these studies was not high enough; therefore, a large multicenter randomized controlled trial is needed to confirm these results.

Preconditioning, a milestone concept in the cardiovascular sciences introduced 32 years back by Murry. This concept opened a new era in the field of organ protection. To start with extensive studies done on ischemic preconditioning for myocardial protection, ischemic preconditioning is an endogenous science of cellular kinetics. Several components in signal transduction cascade have been identified but still some mechanisms not yet revealed. Anesthetic preconditioning also contributed a lot for myocardial protection and concreted the concept of preconditioning. We, with an inquisitive brain meticulously persuing newer methods of cardioprotection. Remote ischemic preconditioning (RIPC) is a brilliant example of it. RIPC can be future of cardioprotection, clinical trials and studies proved the benefits but yet to conclude the superiority of RIPC over myocardial ischemic cardioprotection. This review is an attempt to reveal this extraordinary concept with its basic cellular kinetics, methods, and recent trends. [ABSTRACT FROM AUTHOR]

Мнения исследователей относительно эффективности анестетического прекондиционирования миокарда и головного мозга до сих пор противоречивы. Последний феномен к тому же остается малоизученным. В настоящем исследовании предпринята попытка оценки эффективности модифицированной методики ингаляционной индукции и поддержания анестезии (ИИПА) на основе импульсного дозирования севофлурана и исключающей использование пропофола для защиты миокарда и центральной нервной системы (ЦНС) в процессе выполнения аортокоронарного шунтирования (АКШ) в условиях искусственного кровообращения (ИК) у 90 больных в возрасте от 45 до 75 лет. В группе исследования (ИИПА) осуществляли индукцию севофлураном и моделировали прекондиционирование за 10 мин до пережатия аорты (2 МАК анестетика). На этапе ИК применяли атаралгезию. В группе сравнения (тотальная внутривенная анестезия, ТВА) индукцию и поддержание анестезии осуществляли пропофолом и фентанилом, ингаляционные анестетики не применяли. Результаты обработаны методами вариационной статистики и представлены как M. Межгрупповое сравнение производили с помощью t-критерия Стьюдента или U-критерия Манна - Уитни. Статистически значимыми считали различия при p

Purpose Pre and post-operative administration of sevoflurane in myocardial revascularization surgery provides enhanced cardioprotective effects exerted by pharmacologic pre- and post-conditioning, as compared to propofol. The identification of the enzymes involved in conditioning mechanisms is crucial to the understanding of the effects of sevoflurane in cardiac surgery patients. The impact of sevoflurane on another crucial target organ—the kidney—was also assessed. Methods Ninety patients undergoing off-pump myocardial revascularization surgery were allocated to receive either intra- and postoperative sevoflurane (SS), intraoperative sevoflurane and postoperative propofol (SP), or intra- and postoperative propofol (PP)). Troponin I and hemodynamic parameters were monitored during the first 48 postoperative hours; blood and urine samples were collected at baseline and at 24 h to determine Akt, ERK1/2, PKG, iNO, bradykinin receptor, caspase 3, NT proBNP and urinary NGAL. Results The enzymes were overexpressed in the SS group, remained unchanged in the SP group, and decreased in the PP group. Renal function was best preserved in the SS group. Conclusions The overexpression of enzymes induced by intraoperative anesthesia and postoperative sedation with sevoflurane reduces myocardial damage and improves renal function in patients undergoing off-pump myocardial revascularization surgery. [ABSTRACT FROM AUTHOR]

Background: In animal studies, remote ischemic preconditioning (RIPC) and anesthetic preconditioning are successful in reducing renal ischemia reperfusion injury (IRI), however the protective effect of RIPC may be improved by repeating the RIPC stimulus. Methods: Sprague-Dawley rats underwent unilateral nephrectomy followed by 30 min of renal pedicle clamping. Animals were allocated into six groups: sham, control (IRI), RepISO (daily isoflurane anesthesia), RIPC (single dose isoflurane anesthesia and single dose RIPC), RepISO + RIPC (7-day isoflurane anesthesia and single dose RIPC) and RepISO + RepRIPC (7-day isoflurane anesthesia with 7-day RIPC). RIPC was applied by 3x5 min of cuff inflation on both thighs. Serum creatinine and urea levels were measured and histology was obtained at day two. Results: RepISO diminished renal IRI, as reflected by a significant reduction in serum creatinine levels as compared to the control group, 170 ± 74 resp. 107 ± 29 µmol/L. The other preconditioning protocols showed similar reduction in serum creatinine levels as compared to the control group. No significant differences were observed between the different preconditioning protocols. For urea levels, only RepISO + RIPC resulted in significantly lower levels as compared to the control group, 14 ± 4 resp. 22 ± 7 mmol/L (p = 0.010). In the preconditioning groups only RepISO showed less histological damage as compared to controls 1.73 ± 1.19 resp. 2.91 ± 1.22 (p = 0.032). Conclusions: In this study no additional protective effect of repeated ischemic preconditioning was observed as compared to single dose RIPC. Repeated administration of isoflurane provided stronger protection against renal IRI as compared to single dose isoflurane. [ABSTRACT FROM AUTHOR]

Purpose: The glycocalyx is a glycoprotein-polysaccaride layer covering the endothelium luminal surface, and plays a key regulatory role in several endothelial functions. Lung ischemia reperfusion (IR) is a clinical entity that occurs in everyday thoracic surgery and causes glycocalix destruction and a florid local and systemic immune response. Moreover, sevoflurane is able to modulate the inflammatory response triggered by IR lung injury. In this study, we evaluated the protective effects of sevoflurane on the pulmonary endothelial glycocalyx in an in-vivo lung autotransplant model in pigs. Methods: Sixteen Large White pigs underwent pneumonectomy plus lung autotransplant. They were divided into two groups depending on the hypnotic agent received (propofol or anesthetic preconditioning with sevoflurane). Glycocalyx components (syndecan-1 and heparan sulphate), cathepsin B, chemokines (MCP-1, MIP-1, and MIP-2) and adhesion molecules (VCAM and ICAM-1) were measured at four different timepoints using porcine-specific enzyme-linked immunosorbent assay (ELISA) kits. Results: There were no differences between groups in weight or in surgical and one-lung ventilation time. Greater glycocalyx destruction and higher chemokine and adhesion molecule expression were observed in the group that did not receive sevoflurane. Heparan sulphate and serum syndecan levels were higher in the propofol group ( P < 0.0001) after reperfusion, as was cathepsin B activity ( P < 0.015). MCP-1, MIP-1, MIP-2, VCAM, and ICAM-1 levels were also higher in the propofol group ( P < 0.006). Conclusion: Sevoflurane preconditioning protects pulmonary glycocalyx and reduces expression of leukocyte chemokines in an in-vivo model of pulmonary IR. [ABSTRACT FROM AUTHOR]

Anesthesia profoundly impacts peri-infarct depolarizations (PIDs), but only one prior report has described their monitoring during experimental stroke in awake animals. Since temporal patterns of PID occurrence are model specific, the current study examined PID incidence during focal ischemia in the awake Spontaneously Hypertensive Rat (SHR), and documented the impact of both prior and concurrent isoflurane anesthesia. For awake recordings, electrodes were implanted under isoflurane anesthesia 1 day to 5 weeks prior to occlusion surgery. Rats were then subjected to permanent or transient (2 h) tandem occlusion of the middle cerebral and ipsilateral common carotid arteries, followed by PID monitoring for up to 3 days. Comparison perfusion imaging studies evaluated PID-associated hyperemic transients during permanent ischemia under anesthesia at varied intervals following prior isoflurane exposure. Prior anesthesia attenuated PID number at intervals up to 1 week, establishing 2 weeks as a practical recovery duration following surgical preparation to avoid isoflurane preconditioning effects. PIDs in awake SHR were limited to the first 4 h after permanent occlusions. Maintaining anesthesia during this interval reduced PID number, and prolonged their occurrence through several hours following anesthesia termination. Although PID number otherwise correlated with infarct size, PID suppression by anesthesia was not protective in the absence of reperfusion. PIDs persisted up to 36 h after transient occlusions. These results differ markedly from the one previous report of such monitoring in awake Sprague–Dawley rats, which found an extended biphasic PID time course during 24 h after both permanent and transient filament occlusions. PID occurrence closely reflects the time course of infarct progression in the respective models, and may be more useful than absolute PID number as an index of ongoing pathology. [ABSTRACT FROM AUTHOR]

Acute hyperglycemia (AHG) decreases the availability of nitric oxide (NO) and impairs anesthetic preconditioning (APC)-elicited protection against myocardial infarction. We investigated whether D-4F, an apolipoprotein A-1 mimetic, rescues the myocardium by promoting APC-induced endothelial NO signaling during AHG. Myocardial infarct size was measured in mice in the absence or presence of APC [isoflurane (1.4%)] with or without AHG [dextrose (2 g/kg ip)] and D-4F (0.12 or 0.6 mg/kg ip). NO production, superoxide generation, protein compartmentalization, and posttranslational endothelial NO synthase (eNOS) modifications were assessed in human coronary artery endothelial cells cultured in 5.5 or 20 mM glucose with or without isoflurane (0.5 mM) in the presence or absence of D-4F (0.5 μg/ml). Myocardial infarct size was significantly decreased by APC (36 ± 3% of risk area) compared with control (54 ± 3%) in the absence, but not presence, of AHG (49 ± 4%). D-4F restored the cardioprotective effect of APC during AHG (36 ± 3% and 30 ± 3%,0.12 and 0.6 mg/kg, respectively), although D-4F alone had no effect on infarct size (53 ± 3%). Isoflurane promoted caveolin-1 and eNOS compartmentalization within endothelial cell caveolae and eNOS dimerization, concomitant with increased NO production (411 ± 28 vs. 68 ± 10 pmol/mg protein in control). These actions were attenuated by AHG (NO production: 264 ± 18 pmol/mg protein). D-4F reduced superoxide generation and enhanced caveolin-1 and eNOS caveolar compartmentalization and posttranslational eNOS modifications, thus restoring NO production during isoflurane and AHG (418 ± 36 pmol/mg protein). In conclusion, D-4F restored the cardioprotective effect of APC during AHG, possibly by decreasing superoxide generation, which promoted isoflurane-induced eNOS signaling and NO biosynthesis. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the hemodynamic effects and myocardial injury using troponin-T and creatine phosphokinase (CPK-MB) with isoflurane and compare it with a control group in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. Design: This prospective, randomized study was performed in patients scheduled for elective OPCAB surgery during February 2007 to February 2009. Setting: Tertiary care, university teaching hospital. Participants: Forty-five patients undergoing elective OPCAB surgery. Interventions: Patients were randomly allotted to receive either isoflurane (inspired concentration between 1.0% and 2.5%) or propofol (1.5 to 3.5 mg/kg/h) during OPCAB surgery. The concentration of these agents was titrated such that the BIS value was maintained between 50 and 60. Measurements and Main Results: The hemodynamic data were measured and recorded after induction of anesthesia (baseline), during the distal anastomosis of each coronary artery, and 5 and 30 minutes after giving protamine. In addition, blood samples for troponin-T and CPK-MB were obtained after induction (baseline), after 6 hours and 24 hours postoperatively. The cardiac index was significantly higher in the isoflurane group at all stages, except during distal anastomosis of the diagonal branch of the left anterior descending artery (p < 0.05). There was a significant increase in troponin-T levels at 6 and 24 hours after surgery in the propofol group (from 0.037 ± 0.013 ng/mL to 0.098 ± 0.045 ng/mL and 0.081± 0.025 ng/mL, respectively, p < 0.05). Significant increases in the troponin-T levels were observed at 6 hours (from 0.033 ± 0.011 ng/mL to 0.052 ± 0.025 ng/mL, (p < 0.05) in the isoflurane group, and the levels in the propofol group were significantly higher than the isoflurane group at 6 and 24 hours after surgery (p < 0.05). The CPK-MB levels increased in both groups, but were not statistically different. Conclusions: Isoflurane provides protection against myocardial damage in a clinically used dosage as documented by lower levels of troponin-T in patients undergoing OPCAB surgery. [Copyright &y& Elsevier]

Objective: Opioids, including remifentanil, have been demonstrated to confer cardiac protection against ischemia reperfusion injury in animals. This study evaluated whether remifentanil preconditioning is protective in first-time elective on-pump coronary artery bypass surgery patients receiving a standardized fentanyl (25 μg/kg in total) and propofol anesthetic. Design: A prospective, double blind, randomized, controlled study. Setting: University hospital; single institution. Participants: Forty patients scheduled for first-time elective, on-pump coronary artery bypass surgery for at least 3 diseased vessels. Interventions: Patients randomized to the remifentanil group (n = 20) received a 1 μg/kg bolus followed by a 0.5 μg/kg/min infusion for 30 minutes after induction but before sternotomy, while the control group (n = 20) received normal saline. Serial samples for measurement of creatine kinase (CK-MB), cardiac troponin I (cTnI), ischemia-modified albumin (IMA) and heart-type fatty-acid-binding protein (hFABP) were taken at baseline, prebypass, T = 10 minutes, 2, 6, 12, and 24 hours after cross-clamp release, to assess the degree of myocardial damage. Measurements and Main Results: Patients in the remifentanil group had lower levels of CK-MB from T = 2 hours to 24 hours, cTnI from T = 10 minutes to T = 12 hours, IMA from T = 10 minutes to T = 2 hours and h-FABP from T = 10 minutes to T = 12 hours (p < 0.05). The time to tracheal extubation was shorter in patients in the remifentanil group. The overall lengths of ICU and hospital stays were not different. Conclusions: The addition of remifentanil to the anesthesia regimen reduced the degree of myocardial damage. This incremental benefit may be attributable either to remifentanil itself or to an overall increased opioid dose, the latter may be necessary to trigger cardiac protection. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate whether adding emulsified isoflurane to St Thomas cardioplegia solution could enhance the cardiac protection after cardioplegic arrest in rats. Design: A randomized, blind study. Setting: A university laboratory. Participants: Thirty male Sprague-Dawley rats. Interventions: Thirty isolated heart preparations were randomly divided into 3 groups (n = 10/group) according to the different cardioplegia solutions being given: St Thomas solution mixed with emulsified isoflurane (containing 2.8% of isoflurane, group EI), St Thomas solution mixed with emulsified Intralipid (Huarui Pharmacy, Wuxi, Jiangsu, China) (group EL), and St Thomas solution alone (group St). In the 35-minute normothermic ischemia period, infusion of cardioplegia solution was repeated every 15 minutes. After the 35-minute ischemia period, the heart was perfused with Krebs-Henseleit buffer for another 2 hours. Measurements and Main Results: The functional parameters of the heart were monitored throughout the experiments. The coronary effluent was collected for measuring the activity of CK-MB 30 minutes after reperfusion, and the infarct size was assessed at the end of reperfusion. The infarct size in group EI (24% ± 4%) was reduced when compared with that in group EL (31% ± 8%, p < 0.05) and group St (43% ± 9%, p < 0.001). The CK-MB activity in group EI was decreased significantly when compared with that in group EL and group St (p < 0.05). The functional recovery in group EI also was improved. Compared with standard St Thomas solution alone, adding 30% Intralipid alone also significantly reduced the infarct size and the CK-MB leakage and improved the recovery of the mechanical function. Conclusions: St Thomas cardioplegia solution supplemented with emulsified isoflurane enhanced its cardioprotection in an isolated heart ischemia reperfusion injury model in rats. [Copyright &y& Elsevier]

Abstract: From single to multicellular organisms, protective mechanisms have evolved against endogenous and exogenous noxious stimuli. Preconditioning paradigms, in which stimulation below the threshold of injury results in subsequent protection of the brain, have played an important role in elucidating such endogenous protective mechanisms. Consequently, over the past decades numerous signaling pathways have been discovered by which the brain senses and reacts to such insults as neurotoxins, substrate deprivation, or inflammation. Research on preconditioning is aimed at understanding endogenous neuroprotection to boost it, or to supplement its effectors therapeutically once damage to the brain has occurred, such as after stroke or brain trauma. Another goal of establishing preconditioning protocols is to induce endogenous neuroprotection in anticipation of incipient brain damage. Currently several endogenous neuroprotectants are being investigated in controlled clinical trials. In the present review we will give a short overview on the signals, sensors, transducers, and effectors of endogenous neuroprotection. We will first focus on common mechanisms, on which pathways of endogenous neuroprotection converge, and in particular on mitochondria, which may be considered master integrators of endogenous neuroprotection. We will then discuss various applications of preconditioning, including pharmacological and anesthetic preconditioning, as well as postconditioning, and explore the prospects of endogenous neuroprotective therapeutic approaches. [Copyright &y& Elsevier]

Nitric oxide (NO), when produced via inducible NO synthase (iNOS) in excess under pathological conditions (e.g., inflammation, endotoxemia, and septic shock), may lead to tissue injury and organ dysfunction. The bioavailability of NO and the activity and expression of iNOS are regulated by anesthetic agents. Volatile anesthetics mostly suppress, but in some instances may upregulate, the lipopolysaccharide-and cytokine-induced expression of iNOS in blood vessels and macrophages. Intravenous anesthetics inhibit iNOS expression in macrophages and the liver. Local anesthetics decrease the production of NO by inhibiting iNOS expression in macrophages and increase NO production in glial cells. Based on the literature reported so far, the effects of anesthetics on iNOS expression and activity under conditions of inflammation are controversial, with the observed effects depending on the experimental methods and animal species used. On the other hand, it has been shown that volatile and intravenous anesthetics consistently prevent the development of multiple organ failure elicited by endotoxemia or septic shock. Information, although still insufficient, regarding the interactions between anesthetic agents and the detrimental effects of NO formed during inflammatory processes may help us to construct advanced strategies for anesthetizing and sedating patients with inflammation and sepsis and for anesthetic preconditioning against ischemic injury. [ABSTRACT FROM AUTHOR]

Objectives: Experimental studies have shown that opioids protect the myocardium from ischemic injury and that opioid cardioprotection is enhanced by the coadministration of volatile anesthetics. Previous data suggest that morphine produces a more potent cardioprotective effect than fentanyl. The present study investigated the effect of the choice of intraoperative opioid (morphine or fentanyl) on recovery of myocardial function after coronary artery bypass graft (CABG) surgery. Design: Prospective, randomized study. Setting: University hospital. Participants: Forty-six patients undergoing CABG surgery. Interventions: Patients were randomly assigned to receive either morphine (40 mg) or fentanyl (1,000 μg) before cardiopulmonary bypass (CPB). Global cardiac function was assessed intraoperatively using the myocardial performance index (MPI), which combines echocardiographic parameters of both systolic and diastolic function. Measurements and Main Results: The MPI (median [range]) was increased after CPB in the fentanyl group, indicating a significant worsening of global left ventricular function (0.43 [0.28-0.54] baseline; 0.49 [0.32-0.64] 15 minutes post-CPB; 0.51 [0.36-0.63] end of operation; p < 0.05 post-CPB compared with baseline). The MPI improved in the morphine group after CPB (0.44 [0.32-0.64] baseline; 0.36 [0.24-0.45] 15 minutes post-CPB; 0.34 [0.20-0.46] end of operation; p < 0.05 post-CPB compared with baseline and the fentanyl group). Conclusions: In patients undergoing CPB, global ventricular function is enhanced by the administration of morphine prior to the ischemic insult of cardioplegic arrest. [Copyright &y& Elsevier]

Mitochondria play an important role in tissue ischemia and reperfusion (IR) injury, with energetic failure and the opening of the mitochondrial permeability transition pore being the major causes of IR-induced cell death. Thus, mitochondria are an appropriate focus for strategies to protect against IR injury. Two widely studied paradigms of IR protection, particularly in the field of cardiac IR, are ischemic preconditioning (IPC) and volatile anesthetic preconditioning (APC). While the molecular mechanisms recruited by these protective paradigms are not fully elucidated, a commonality is the involvement of mitochondrial K + channel opening. In the case of IPC, research has focused on a mitochondrial ATP-sensitive K + channel (mitoK ATP ), but, despite recent progress, the molecular identity of this channel remains a subject of contention. In the case of APC, early research suggested the existence of a mitochondrial large-conductance K + (BK, big conductance of potassium) channel encoded by the Kcnma1 gene, although more recent work has shown that the channel that underlies APC is in fact encoded by Kcnt2 In this review, we discuss both the pharmacologic and genetic evidence for the existence and identity of mitochondrial K + channels, and the role of these channels both in IR protection and in regulating normal mitochondrial function., (© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.)