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Anesth Analg 2003;96:949-955 © 2003 International Anesthesia Research Society
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Abstract |
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Reactive oxygen species (ROS) are largely responsible for cardiac injury consequent to ischemia and reperfusion, but, paradoxically, there is evidence suggesting that anesthetics induce preconditioning (APC) by generating ROS. We hypothesized that sevoflurane generates the ROS superoxide (O2·-), that APC attenuates O2·- formation during ischemia, and that this attenuation is reversed by bracketing APC with the O2·- scavenger manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) or the putative mitochondrial adenosine triphosphate-sensitive potassium (mKATP) channel blocker 5-hydroxydecanoate (5-HD). O2·- was measured continuously in guinea pig hearts by using dihydroethidium. Sevoflurane was administered alone (APC), with MnTBAP, or with 5-HD before 30 min of ischemia and 120 min of reperfusion. Control hearts underwent no pretreatment. Sevoflurane directly increased O2·-; this was blocked by MnTBAP but not by 5-HD. O2·- increased during ischemia and during reperfusion. These increases in O2·- were attenuated in the APC group, but this was prevented by MnTBAP or 5-HD. We conclude that sevoflurane directly induces O2·- formation but that O2·- formation is decreased during subsequent ischemia and reperfusion. The former effect appears independent of mKATP channels, but not the latter. Our study indicates that APC is initiated by ROS that in turn cause mKATP channel opening. Although there appears to be a paradoxical role for ROS in triggering and mediating APC, a possible mechanism is offered.
IMPLICATIONS: Reactive oxygen species (ROS) are implicated in triggering anesthetic preconditioning (APC). The ROS superoxide (O2·-) was measured continuously in guinea pig isolated hearts. Sevoflurane directly increased O2·- but led to attenuated O2·- formation during ischemia. This demonstrates triggering of APC by ROS and clarifies the mechanism of cardioprotection during ischemia.
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Introduction |
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Anesthetic preconditioning (APC) describes the phenomenon whereby brief exposure of the heart to a volatile anesthetic induces a state of protection against the effects of ischemia/reperfusion injury (1–5) . This protection is manifested by decreased myocardial stunning, decreased arrhythmias, and decreased infarction after ischemia/reperfusion. There is indirect evidence that anesthetics cause the release of reactive oxygen species (ROS) to trigger APC, because the protective effects of APC were abolished when ROS scavengers were given during anesthetic exposure (2,3) . In addition, a reduction in ROS formation appears to mediate, at least in part, the reduced tissue injury during ischemia and reperfusion because APC attenuated the release of oxidation products during reperfusion (3).
There is now evidence that significant ROS formation occurs during ischemia before reperfusion (6–8) . The mitochondrial electron transport chain is believed to be the principle source of ROS during ischemia in cardiac cells (7) and may also be the source of the postulated ROS formation during anesthetic exposure, because anesthetics are known to alter several indices of electron transport chain function (4,9,10) . We have recently shown in intact hearts that APC leads to more normalized nicotinamide-adenine dinucleotide (NADH) (4) and attenuated mitochondrial Ca2+ loading (5) during isch-emia and that APC leads to reduced ROS release from intact hearts (3) and to less ROS formation in isolated mitochondria during reperfusion (11). These findings suggest that improved mitochondrial bioenergetics during ischemia or reperfusion is a feature of APC and is likely to underlie the global functional and structural preservation. Suppressed electron transport chain activity (i.e., more normalized NADH) (4) during ischemia would lead to decreased superoxide (O2·-) formation, the principle progenitor ROS formed by mitochondrial enzyme complexes. Thus, a volatile anesthetic may paradoxically stimulate O2·- formation, leading to activation of protective mechanisms that ultimately lead to decreased O2·- formation by the mitochondrion during ischemia.
There is evidence to link ROS with several mediators implicated in preconditioning, particularly the mitochondrial adenosine triphosphate-sensitive potassium (mKATP) channel (12). There is conflicting evidence, however, on the relative sequence of ROS formation and mKATP opening (12,13) . We and others have shown that the cardioprotective effects of APC can be inhibited by either ROS scavengers (2,3) or mKATP channel blockers (5,14–16) . In this study, we hypothesized first that O2·- is generated during anesthetic exposure and that this is not inhibited by mKATP channel blockade, indicating an initiating role for ROS and a downstream role for the mKATP channel in APC. We hypothesized second that the O2·- generation then leads to preservation of electron transport chain function via mKATP opening during subsequent ischemia, i.e., manifested by reduced O2·- not only during reperfusion, but also during ischemia. To examine these hypotheses, we measured O2·- formation in real time in isolated guinea pig hearts by spectrofluorometry via a probe placed at the left ventricular free wall and the fluorescent probe dihydroethidium (DHE).
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Methods |
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The investigation conformed to the Guide for the Care and Use of Laboratory Animals (US National Institutes of Health publication No. 85-23, revised 1996). Approval was obtained from the Medical College of Wisconsin animal studies committee. Our preparation has been described in detail previously (3–5,17) . Guinea pig hearts (n = 70) were isolated and perfused at constant pressure (55 mm Hg) at 37°C with an oxygenated Krebs-Ringer (KR) solution with a pH of 7.4 and of the following composition (mM): Na+ 138, K+ 4.5, Mg2+ 1.2, Ca2+ 2.5, Cl- 134, HCO3- 14.5, H2PO4- 1.2, glucose 11.5, pyruvate 2, mannitol 16, probenecid 0.1, and EDTA 0.05, as well as insulin 5 U/L.
Diastolic and systolic left ventricular pressure (LVP) were measured isovolumetrically by using a transducer connected to a saline-filled latex balloon placed in the left ventricle. Balloon volume was adjusted to a diastolic LVP of 0 mm Hg during the initial equilibration period. Coronary inflow (CF) was measured by an ultrasonic flowmeter (Transonic T106X; Transonic, Ithaca, NY). Atrial and ventricular bipolar leads were used to measure spontaneous heart rate. CF and coronary venous Na+, K+, Ca2+, PO2, pH, and PCO2 were measured off-line with an intermittently self-calibrating analyzer (Radiometer ABL 505; Radiometer, Copenhagen, Denmark). Coronary sinus PO2 tension (PvO2) was also measured continuously on-line with a Clark electrode (Model 203B; Instech, Plymouth Meeting, PA). Myocardial oxygen consumption was calculated as CF/heart weight (g) · (PaO2 - PvO2) · 24 mL/µL of oxygen at 760 mm Hg.
Sevoflurane was bubbled into the perfusate with an agent-specific vaporizer. Sevoflurane concentrations in KR were measured by gas chromatography from samples taken anaerobically from the inflow line just proximal to the flowprobe. Global ischemia was achieved by clamping the inflow line. If ventricular fibrillation occurred on reperfusion, a bolus of lidocaine (250 µg) was given via a side port of the aortic inflow cannula. After 120 min of reperfusion, hearts were removed, and the ventricles were cut into six transverse sections and stained with 1% 2,3,5-triphenyltetrazolium chloride in 0.1 M KH2PO4 buffer (pH 7.4; 38°C). Tissue was stored in 10% formaldehyde for 48 h before dissection in a blinded fashion. Infarct size was expressed as a percentage of total ventricular weight (3). The average total ventricular weight was 1.7 ± 0.1 g (mean ± SEM), with no differences among groups.
We have previously described in detail our application of fluorescence techniques in intact hearts for measurements of cytosolic Ca2+ (17), mitochondrial Ca2+ (5), Na+ (17), and NADH (4,16) . Briefly, the distal end of a trifurcated fiberoptic cable (optical surface area 3.85 mm2) was placed against the LV free wall through a hole in the tissue bath. The fiberoptic cable was connected to a modified spectrophotometer (SLM Aminco-Bowman II; Spectronic Instruments, Urbana, IL). The fluorescent dye DHE (Molecular Probes, Eugene, OR) was dissolved in dimethyl sulfoxide containing 16% (wt/vol) Pluronic I-127 (Sigma Chemical, St. Louis, MO) and made up in 300 mL of KR, for a final concentration of 10 µM DHE and 10-3 M dimethyl sulfoxide. DHE enters cells and, when oxidized by ROS with a relative selectivity for O2·- (7), is converted to ethidium (ETH); ETH intercalates with DNA, causing the nucleus to exhibit red fluorescence. The fluorescent intensity (FI) of ETH (ETH FI) was measured in a light-blocking Faraday cage at an emission wavelength of 590 nm (bandwidth, 4 nm), amplified by a photomultiplier tube (700 V), and recorded after excitation with a 150 W xenon arc lamp filtered at 540 nm (bandwidth, 4 nm). The excitation wavelength penetrates the whole 4 mm of the ventricular wall.
In preliminary experiments (n = 4), background changes in FI (DHE vehicle) were determined for each experimental protocol. 5-Hydroxydecanoate (5-HD) and manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP; OxisResearch, Portland, OR) had no effect on background fluorescence, and ischemia/reperfusion had a minimal (nonsignificant) effect (<5% of the value obtained with DHE). All subsequent recorded values of ETH FI were adjusted for the minimal change in background fluorescence obtained during ischemia and reperfusion. Hearts were loaded with DHE in KR for 25 min, followed by washout of residual DHE with standard KR for 15 min. Loading of DHE was found to increase diastolic LVP approximately 8% and to increase CF approximately 10%; the effect on diastolic LVP was partly (but incompletely) reversed by washout, and CF returned to baseline values. DHE loading increased FI from 0.04 ± 0.01 (mean ± SEM) before loading to 2.1 ± 0.3 arbitrary units after washout. Each washout value was adjusted to 0 arbitrary units for normalizing FI values for all experiments.
In preliminary experiments (n = 8), the specificity of ETH FI for O2·- and the effects of possible sources of artifact, including movement-induced changes in LVP, pH, and flow, were studied. A rate increase to 375 bpm by isoproterenol and a decrease to 125 bpm by labetalol did not affect ETH FI, nor did pH in the range 6.2–8.0 or mechanically altered flow between 5 and 20 mL · g-1 · min-1. Brief pharmacologic arrest induced with adenosine had no effect on FI. Endogenous generation of O2·- by using the mitochondrial electron transport chain inhibitors rotenone (10 µM) and antimycin A (10 µM) was found to increase ETH FI by 21% and 82% from baseline, respectively. The administration of H2O2 (10–100 µM) did not affect ETH FI, whereas H2O2 caused significant dose-dependent increases (3%–36%) in the FI of dichorohydro-fluoroscein, which has a higher specificity for H2O2 and hydroxyl radical (OH·-) than for O2·-.
There were 6 experimental groups (n = 8 per group) and a time-control group (n = 6). Each experiment lasted 190 min after a 30-min equilibration period, a 25-min DHE-loading period, and a 15-min washout period. The ischemia control group (ISC) underwent only 30 min of ischemia and 120 min of reperfusion. Cardiac preconditioning consisted of two 5-min pulses of sevoflurane with an intervening 5-min perfusion period with KR and a 20-min perfusion period before ischemia (APC). The inflow sevoflurane concentration was 0.52 ± 0.02 mM (mean ± SEM) (or 3.6%) at 37°C (there was no difference among groups exposed to sevoflurane). In the APC plus MnTBAP and APC plus 5-HD groups, 20 µM of the ROS scavenger MnTBAP or 200 µM of the putative mKATP channel blocker 5-HD was given from 5 min before the first preconditioning pulse, during the intervening washout period, and for 5 min after the conclusion of the second APC pulse before ischemia. In the MnTBAP and 5-HD groups, either drug was given continuously for 25 min without sevoflurane, followed by a 15-min washout before ischemia. ETH FI was sampled for 100 ms during each recording. This was repeated every 12 s throughout the entire experimental protocol, for a total fluorescence recording time of 95 s. In four additional hearts, the effect of 0.82 ± 0.03 mM (mean ± SEM) sevoflurane (5.7%) on ETH FI was evaluated in the absence and presence of 20 µM MnTBAP or 200 µM 5-HD.
All data are expressed as mean ± SE. Within-group data were compared with those of a time-control group at the following time points: baseline (0 min), during and after the preconditioning stimuli, during ischemia at 5-min intervals, during reperfusion at 5-min intervals to 15 min of reperfusion, and at 60 and 120 min of reperfusion. Among-group data were compared at the same time points. Comparisons were made by using analysis of variance with the Student-Newman-Keuls test as the post hoc test (Prism Version 3.0a; GraphPad Software Inc, San Diego, CA). Differences among means were considered statistically significant at P < 0.05 (two tailed).
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Results |
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Baseline values were similar for all groups. Table 1 and Figure 1 show that APC led to improved developed and diastolic LVP, CF, and myocardial oxygen consumption on reperfusion and to decreased infarct size compared with ISC. When sevoflurane exposure was bracketed with 5-HD (APC plus 5-HD) or MnTBAP (APC plus MnTBAP), the reperfusion values obtained were similar to those of the ISC group. During exposure to 0.52 ± 0.02 mM sevoflurane, as applied to the APC, APC plus 5-HD, and APC plus MnTBAP groups, sensitivity was not sufficient to detect changes in ETH FI.
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During early ischemia, ETH FI increased approximately 40% above baseline values in the ISC group and stabilized; ETH FI then increased further after 20 min and on reperfusion (Fig. 2A). In the APC group, ETH FI increased during the first 20 min of ischemia, as in the ISC group, but ETH FI remained significantly attenuated thereafter and during reperfusion compared with the ISC group. In the APC plus 5-HD and APC plus MnTBAP groups and in the 5-HD and MnTBAP groups, changes in ETH FI during ischemia and reperfusion were similar to those in the ISC group. To control for a possible decrease in the intracellular-extracellular volume ratio due to rapid restitution of flow at early reperfusion, ETH FI values were corrected for flow. Figure 2B shows that the brief apparent decline in intracellular ROS on initial reperfusion likely represents such a change in the fluid compartment ratio, but differences between APC and each of the other ischemia groups remained after this adjustment.
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During exposure of hearts to 0.82 ± 0.03 mM sevoflurane, ETH FI increased significantly by approximately 10% of that found during 5–20 min of ischemia (Fig. 3A). 5-HD had no effect on ETH FI during sevoflurane exposure (Fig. 3B) (or when given alone), whereas MnTBAP obliterated this increase in ETH FI (Fig. 3C). These changes in ETH FI were independent of any change in CF because they occurred similarly when flow was fixed at 8 mL · min-1 · g-1. Figure 3D shows a bar chart of time-averaged ETH FI during each of the conditions: baseline, sevoflurane exposure, and sevoflurane with 5-HD or MnTBAP (n = 4).
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Discussion |
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We (3) and others (2) have previously reported that ROS are involved in the triggering of APC. In this study, we directly demonstrated ROS generation during sevoflurane exposure and clarified part of the cell-signaling sequence of APC. Overall, our results suggest that ROS elicit mKATP opening. We also demonstrated that APC leads to reduced ROS formation, not only during reperfusion, but also during ischemia. Together with our previous reports of altered NADH levels (4) and reduced mitochondrial Ca2+ loading during ischemia (5), these results indicate that altered mitochondrial bioenergetics during ischemia are a key characteristic of APC-induced cardioprotection. Similar to the ROS scavenger MnTBAP, the mKATP channel inhibitor 5-HD also abrogated the effects of APC to attenuate O2·- formation during ischemia and reperfusion. Importantly, however, 5-HD had no effect on O2·- formation during sevoflurane exposure. This suggests that mKATP channel opening does not trigger APC, but rather is a downstream event of ROS formation that leads to subsequent reduction in ROS formation during ischemia and reperfusion.
Intracellular oxygen decreases during ischemia, but absolute anoxia does not occur in the intact heart (18). Decreases in substrate gradients and electron transport chain dysfunction during ischemia lead to O2·- production from residual oxygen by enzyme complexes of the electron transport chain (7,8) . Prior evidence of ROS formation during ischemia included the finding of oxidant injury in cardiac tissues subject to ischemia without reperfusion (19). More recently, ROS formation during ischemia has been demonstrated directly in cardiomyocytes (7,8) and in intact animals (6). Most evidence points to the mitochondrion as the prime source of ROS within myocytes (7,20) , although other sources are possible, including endothelial xanthine oxidase and macrophages. We have previously shown that APC decreases the reperfusion release of dityrosine, a marker of oxidization by ROS and reactive nitrogen species (3). This study extends these findings by identifying O2·- as the initial ROS modulated by APC and by showing that significant alterations to O2·- production occur during ischemia, as well as during reperfusion.
Abrogation of APC-induced infarct-size reduction by ROS scavengers has been demonstrated previously (2,3) . This implies an effect of anesthetics to generate ROS, as directly demonstrated here and as previously suggested on the basis of indirect measures in blood vessels (21,22) . Because of the limits of our detection system for ETH fluorescence, we had to use a larger concentration of sevoflurane to demonstrate an increase in the fluorescent signal produced by sevo- flurane. However, the smaller concentration was sufficient to induce preconditioning, and we have shown previously that a larger concentration similarly induces APC (5). The relative quantity of intracellular ROS formed in response to anesthetic exposure at the larger dose was <10% of that during initial ischemia; at the smaller concentration used to initiate APC, it was probably proportionately smaller and outside our detection limit. Although we cannot exclude the possibility, on the basis of our direct measurements, that O2·- generation did not occur at the smaller concentration of sevoflurane, at this smaller concentration the O2·- scavenger MnTBAP was found to inhibit preconditioning, strongly suggesting the presence of O2·- and confirming its triggering role.
It is not known how anesthetics generate ROS, although reported effects of anesthetics on indices of mitochondrial electron transport chain function (4,9,10) strongly implicate the electron transport chain as the site of action. It was suggested more than 25 years ago that volatile anesthetics might interfere with NADH oxidoreductase activity (10), and subsequently NADH was shown to increase in response to volatile anesthetics in rat hearts (23). Nonetheless, our measurements do not exclude the possibility of alternative mechanisms of ROS formation; for example, radical intermediates of halothane are produced by hepatocytes (24). A similar reaction in myocytes with sevoflurane appears unlikely to us, however.
Several reports demonstrate the effect of ROS to induce preconditioning (2,3,8) , but it is not known how ROS, generated by anesthetics or by other stimuli, lead to preconditioning. ROS are protean cellular messengers in the heart, and there is evidence to link ROS with several mediators implicated in preconditioning, including the mKATP channel (12), protein kinase C (12), and others. Our results with the putative mKATP channel blocker 5-HD suggest that this channel is not required for O2·- generation in response to anesthetic exposure, because ETH FI during sevoflurane exposure was unaffected by concomitant administration of 5-HD. Attenuation of O2·- formation during subsequent ischemia by APC may require opening of this channel, however, because ETH FI during ischemia and reperfusion in the APC plus 5-HD group was similar to that in the ISC group. This is consistent with previous work that suggested that the preconditioning pathway involves the opening of the mKATP channel in response to ROS (12). Alternatively, it has been suggested that the converse occurs, i.e., that mKATP channel opening leads to the formation of ROS (13). The opening of the mKATP channel has been proposed to optimize mitochondrial bioenergetics by causing partial dissipation of the mitochondrial membrane potential and subsequent swelling of the mitochondrial matrix (25). Nonetheless, it is important to note that non-mKATP channel effects of 5-HD have been reported recently (26), and further work will be required to delineate the role of mKATP channels in preconditioning.
Limitations of our measure of O2·- are that an exact calibration technique is unavailable and that we cannot determine the specific reactive species that triggers preconditioning. It is possible that downstream products of O2·-, such as H2O2 or OH·, are the specific trigger of the pathway that leads to APC. Indeed, there is evidence in cardiomyocytes that dismutation of O2·- is a necessary step for preconditioning (8). Moreover, OH· has been reported to decrease ETH FI (7) and could have contributed to the decreased ETH FI that we observed during early reperfusion, as similarly reported by Becker et al. (7) during reoxygenation of anoxic myocytes.
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Summary |
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TopAbstractIntroductionMethodsResultsDiscussionSummaryReferences |
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We found that sevoflurane directly caused O2·- formation and that APC was characterized by attenuated O2·- formation during subsequent ischemia and reperfusion. The opening of the mKATP channel appears to be required for ROS to elicit protection during ischemia. Consistent with our recent findings of altered mitochondrial function during ischemia and reperfusion after APC, these results indicate that APC preserves mitochondrial energetics during ischemia and suggest that this largely underlies the global cardiac functional and structural preservation that characterizes APC. This study offers a clear demonstration of the paradoxical role of ROS both in triggering and in mediating APC-induced cardioprotection.
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Acknowledgments |
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Supported in part by National Institutes of Health Grants HL-58691 and GM-8204-06, by American Heart Association Grant 0360042Z, and by the Department of Veterans Affairs.
The authors thank the following for their contributions to this study: James Heisner, Dr. Ming Tao Jiang, and Anita Tredeau. Portions of this work have appeared in abstract form (Kevin LG, Novalija E, Camara AK, et al. Formation of reactive oxygen species during ischemic and anesthetic preconditioning in isolated hearts. Anesthesiology 2002;96:A80).
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References |
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TopAbstractIntroductionMethodsResultsDiscussionSummaryReferences |
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- Cason BA, Gamperl AK, Slocum RE, Hickey RF. Anesthetic-induced preconditioning: previous administration of isoflurane decreases myocardial infarct size in rabbits. Anesthesiology 1997; 87: 1189–90.
- Mullenheim J, Ebel D, Frabetadorf J, et al. Isoflurane preconditions myocardium against infarction via release of free radicals. Anesthesiology 2002; 96: 934–40.[Web of Science][Medline]
- Novalija E, Varadarajan SG, Camara AKS, et al. Anesthetic preconditioning: triggering role of reactive oxygen and nitrogen species in isolated hearts. Am J Physiol Heart Circ Physiol 2002; 283: H44–52.
[Abstract/Free Full Text] - Riess M, Camara AK, Chen Q, et al. Altered NADH and improved function by anesthetic and ischemic preconditioning in guinea pig intact hearts. Am J Physiol Heart Circ Physiol 2002; 283: H53–60.
[Abstract/Free Full Text] - Riess ML, Camara KS, Novalija E, et al. Anesthetic preconditioning attenuates mitochondrial Ca2+ overload during ischemia in guinea pig intact hearts: reversal by 5-hydroxydecanoic acid. Anesth Analg 2002; 95: 1540–6.
[Abstract/Free Full Text] - O’Neill CA, Fu LW, Halliwell B, Longhurst JC. Hydroxyl radical production during myocardial ischemia and reperfusion in cats. Am J Physiol Heart Circ Physiol 1996; 271: H660–7.
[Abstract/Free Full Text] - Becker LB, Vanden Hoek TL, Shao ZH, et al. Generation of superoxide in cardiomyocytes during ischemia before reperfusion. Am J Physiol Heart Circ Physiol 1999; 277: H2240–6.
[Abstract/Free Full Text] - Vanden Hoek TL, Becker LB, Shao Z, et al. Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J Biol Chem 1998; 273: 18092–8.
[Abstract/Free Full Text] - Harris RA, Munroe J, Farmer B, et al. Action of halothane upon mitochondrial respiration. Arch Biochem Biophys 1971; 142: 435–44.[Medline]
- Nahrwold ML, Clark CR, Cohen PJ. Is depression of mitochondrial respiration a predictor of in-vivo anesthetic activity? Anesthesiology 1974; 40: 566–70.[Medline]
- Novalija E, Kevin LG, Henry MM, et al. Anesthetic preconditioning triggered by reactive oxygen species improves mitochondrial function after ischemia [abstract]. Anesthesiology 2002; 97: A100.
- Zhang HY, McPherson BC, Liu H, et al. H2O2 opens mitochondrial KATP channels and inhibits GABA receptors via protein kinase C-epsilon in cardiomyocytes. Am J Physiol Heart Circ Physiol 2002; 282: H1395–403.
[Abstract/Free Full Text] - Forbes RA, Steenbergen C, Murphy E. Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism. Circ Res 2001; 88: 802–9.
[Abstract/Free Full Text] - Piriou V, Chiari P, Knezynski S, et al. Prevention of isoflurane-induced preconditioning by 5-hydroxydecanoate and gadolinium: possible involvement of mitochondrial adenosine triphosphate-sensitive potassium and stretch-activated channels. Anesthesiology 2000; 93: 756–64.[Web of Science][Medline]
- Toller WG, Gross ER, Kersten JR, et al. Sarcolemmal and mitochondrial adenosine triphosphate-dependent potassium channels: mechanism of desflurane-induced cardioprotection. Anesthesiology 2000; 92: 1731–9.[Web of Science][Medline]
- Riess M, Novalija E, Chen Q, et al. Anesthetic preconditioning reduces changes in NADH during ischemia reperfusion: reversal by 5-hydroxydecanoic acid. Anesthesiology. In press.
- An JZ, Varadarajan SG, Camara A, et al. Blocking Na+/H+ exchange reduces [Na+]i and [Ca2+]i load after ischemia and improves function in intact hearts. Am J Physiol Heart Circ Physiol 2001; 281: H2398–409.
[Abstract/Free Full Text] - Zweier JL, Chzhan M, Ewert U, et al. Development of a highly sensitive probe for measuring oxygen in biological tissues. J Magn Reson B 1994; 105: 52–7.[Web of Science][Medline]
- Bolli R, Patel BS, Jeroudi MO, et al. Demonstration of free radical generation in "stunned" myocardium of intact dogs with the use of the spin trap alpha-phenylN-tert-butyl nitrone. J Clin Invest 1988; 82: 476–85.
- Ambrosio G, Zweier JL, Duilio C, et al. Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow. J Biol Chem 1993; 268: 18532–41.
[Abstract/Free Full Text] - Yoshida K, Okabe E. Selective impairment of endothelium-dependent relaxation by sevoflurane: oxygen free radicals participation. Anesthesiology 1992; 76: 440–7.[Web of Science][Medline]
- Park KW, Dai HB, Lowenstein E, et al. Oxygen-derived free radicals mediate isoflurane-induced vasoconstriction of rabbit coronary resistance arteries. Anesth Analg 1995; 80: 1163–7.[Abstract]
- Kissin I, Aultman DF, Smith LR. Effects of volatile anesthetics on myocardial oxidation-reduction status assessed by NADH fluorometry. Anesthesiology 1983; 59: 447–52.[Web of Science][Medline]
- Plummer JL, Beckwith AL, Bastin FN, et al. Free radical formation in vivo and hepatotoxicity due to anesthesia with halothane. Anesthesiology 1982; 57: 160–6.[Medline]
- Halestrap AP. Regulation of mitochondrial metabolism through changes in matrix volume [review]. Biochem Soc Trans 1994; 22: 522–9.[Web of Science][Medline]
- Hanley PJ, Mickel M, Loffler M, et al. KATP channel-independent targets of diazoxide and 5-hydroxydecanoate in the heart. J Physiol 2002; 542: 735–41.
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R. A. Bouwman, F. N. G. van't Hof, W. de Ruijter, B. J. van Beek-Harmsen, R. J. P. Musters, J. J. de Lange, and C. Boer The mechanism of sevoflurane-induced cardioprotection is independent of the applied ischaemic stimulus in rat trabeculae Br. J. Anaesth., September 1, 2006; 97(3): 307 - 314. [Abstract] [Full Text] [PDF]
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D. Obal, S. Dettwiler, C. Favoccia, H. Scharbatke, B. Preckel, and W. Schlack The Influence of Mitochondrial KATP-Channels in the Cardioprotection of Preconditioning and Postconditioning by Sevoflurane in the Rat In Vivo Anesth. Analg., November 1, 2005; 101(5): 1252 - 1260. [Abstract] [Full Text] [PDF]
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L. G. Kevin, E. Novalija, and D. F. Stowe Reactive Oxygen Species as Mediators of Cardiac Injury and Protection: The Relevance to Anesthesia Practice Anesth. Analg., November 1, 2005; 101(5): 1275 - 1287. [Abstract] [Full Text] [PDF]
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S. G. De Hert, F. Turani, S. Mathur, and D. F. Stowe Cardioprotection with Volatile Anesthetics: Mechanisms and Clinical Implications Anesth. Analg., June 1, 2005; 100(6): 1584 - 1593. [Abstract] [Full Text] [PDF]
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M. L. Riess, L. G. Kevin, J. McCormick, M. T. Jiang, S. S. Rhodes, and D. F. Stowe Anesthetic Preconditioning: The Role of Free Radicals in Sevoflurane-Induced Attenuation of Mitochondrial Electron Transport in Guinea Pig Isolated Hearts Anesth. Analg., January 1, 2005; 100(1): 46 - 53. [Abstract] [Full Text] [PDF]
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M. L. Riess, D. F. Stowe, and D. C. Warltier Cardiac pharmacological preconditioning with volatile anesthetics: from bench to bedside? Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1603 - H1607. [Abstract] [Full Text] [PDF]
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M. L Riess, A. K.S Camara, L. G Kevin, J. An, and D. F Stowe Reduced reactive O2 species formation and preserved mitochondrial NADH and [Ca2+] levels during short-term 17 {degrees}C ischemia in intact hearts Cardiovasc Res, February 15, 2004; 61(3): 580 - 590. [Abstract] [Full Text] [PDF]
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