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Introduction It is highly uncertain whether volatile organic compounds (VOCs) in exhaled breath of critically ill intensive care unit patients are formed in the lung locally, in the air compartment or lung tissue, or elsewhere in the body and transported to the lung via the bloodstream. We compared VOC mixtures in exhaled breath and in air coming from extracorporeal support devices in critically ill patients to address this issue. Methods First, we investigated whether it was safe to connect an electronic nose (eNose) or a gas sampling pump to extracorporeal support membranes. Then, breath and air from extracorporeal support devices were collected simultaneously for continuous monitoring of VOC mixtures using an eNose. In addition, samples for gas chromatography/mass spectrometry (GC-MS) analysis were taken daily at the two measurement sites. Results 10 critically ill patients were monitored for a median (interquartile range) duration of 73 (72–113) h; in total, we had 887 h of air sampling. The eNose signals of breath correlated moderately with signals of air from the extracorporeal support devices (R2=0.25–0.44). After GC-MS analysis, 96 VOCs were found both in breath and air from the extracorporeal support devices; of these, 29 (30%) showed a significant correlation (p, Systemically produced VOCs in exhaled breath and extracorporeal circulation correlate well. About one in three VOCs do not correlate and are found in higher concentrations in breath, suggesting pulmonary production of these VOCs. http://ow.ly/cbjt30nMXY5

Long-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects. All patients treated with CIAN therapy for at least 5 days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2 days before the beginning and 5 days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy. Data from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5 ± 4.5 days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4–5) 6 months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation of a previous antiinfective therapy or the onset of antibiotics which was in line with a significant increase of C-reactive protein and white blood cell count. Obstipation was observed in 22 patients (78.6%). Ten patients (35.7%) even showed insufficient defecation on at least seven consecutive days. Compared to the situation before, ICP was significantly higher during the whole period of CIAN therapy. Long-term CIAN therapy is associated with diverse side effects. The leading problems are an impairment of the hemodynamic situation and cardiac problems, an increase in infectious complications, a worsening of the motility of the gastrointestinal tract, and rising ICP values. Teams on neurointensive care units must be aware of these side effects to avoid that the beneficial effects of CIAN therapy on CV reported elsewhere are foiled by the problems this technique can be associated with.

Wir berichten uber einen Patienten mit Thoraxtrauma, der nach operativer Versorgung auf die Intensivstation aufgenommen wurde. Nach Erfullung entsprechender Protokollkriterien wurde er am 7. postoperativen Tag extubiert, musste aber trotz intermittierender nicht-invasiver Beatmung am 10. Tag bei progressiver Hyperkapnie re-intubiert werden. Wir entschieden uns zu einer extrakorporalen CO2-Elimination (ECCO2‑R) anstelle einer Tracheotomie. Mit einem Blutfluss von 1,5 l/min gelang eine suffiziente CO2-Elimination, sodass der Patient bereits wenige Stunden spater extubiert werden konnte. Nach funf Tagen an ECCO2‑R konnte der Patient vom System entwohnt und stabil auf Normalstation verlegt werden.

Cyclooxygenase (COX)-2 mediates ischemic pre- and postconditioning as well as anesthetic-induced preconditioning. However, the role of COX-1 and -2 in anesthetic-induced postconditioning has not been investigated. We evaluated the role of COX-1 and -2 in sevoflurane-induced postconditioning in vivo. Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45 minutes of coronary artery occlusion and 3 hours of reperfusion. Animals received either no intervention, the vehicle dimethyl sulfoxide (DMSO, 10 µL/g intraperitoneally), acetylsalicylic acid (ASA, 5 µg/g intraperitoneally), the selective COX-1 inhibitor SC-560 (10 µg/g intraperitoneally), or the selective COX-2 inhibitor NS-398 (5 µg/g intraperitoneally). 1.0 MAC (minimum alveolar concentration) sevoflurane was administered for 18 minutes during early reperfusion either alone or in combination with ASA, SC-560, and NS-398. Infarct size was determined with triphenyltetrazolium chloride. Statistical analysis was performed using 1-way and 2-way analyses of variance with post hoc Duncan testing. The infarct size in the control group was 44% ± 9%. DMSO (42% ± 7%), ASA (36% ± 6%), and NS-398 (44% ± 18%) had no effect on infarct size. Sevoflurane (17% ± 4%; P < .05) and SC-560 (26% ± 10%; P < .05) significantly reduced the infarct size compared with control condition. Sevoflurane-induced postconditioning was not abolished by ASA (16% ± 5%) and SC-560 (22% ± 4%). NS-398 abolished sevoflurane-induced postconditioning (33% ± 14%). It was concluded that sevoflurane induces postconditioning in mice. Inhibition of COX-1 elicits a myocardial infarct size reduction and does not abolish sevoflurane-induced postconditioning. Blockade of COX-2 abolishes sevoflurane-induced postconditioning. These results indicate that sevoflurane-induced postconditioning is mediated by COX-2.

Background Anaesthetic-induced (APOST) and ischaemic postconditioning (IPOST) against myocardial infarction are mediated via phosphatidylinositol-3-kinase/Akt. Pim-1 kinase is acting downstream of Akt and has recently been demonstrated to enhance cardiomyocyte survival. We tested the hypothesis that both APOST and IPOST are mediated by Pim-1 kinase. Methods Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45-min coronary artery occlusion (CAO) and 3-h reperfusion. Animals received either no intervention, the Pim-1 kinase inhibitor II (10??g/g intraperitoneally) or its vehicle dimethy sulfoxide (10??l/g intraperitoneally). Three minutes prior to the end of CAO, 1.0 minimum alveolar concentration desflurane was administered for 18?min alone or in combination with Pim-1 kinase inhibitor II. IPOST was induced by three cycles of each 10-s ischaemia/reperfusion, and animals received either IPOST alone or in combination with Pim-1 kinase inhibitor II. Infarct size was determined with triphenyltetrazolium chloride and area at risk with Evans blue. Protein expression of Pim-1 kinase, Bad, phospho-BadSer112 and B-cell lymphoma 2 was determined using Western immunoblotting analysis. Results Infarct size in control animals (CON) was 46?±?3%. Dimethylsulfoxide (47?±?3%) and Pim-1 kinase inhibitor II (44?±?5%) did not significantly reduce infarct size. Desflurane (16?±?2%*; *P? Conclusion These data suggest that Pim-1 kinase mediates both desflurane-induced postconditioning and IPOST in mice.

The second window of anaesthetic-induced preconditioning (APC) is afforded by the interplay of multiple signalling pathways, whereas a similar protective response is mediated by peroxisome-proliferator-activated receptor γ (PPARγ) agonists. However, a possible role of this nuclear receptor during APC has not been studied to date. We investigated the hypothesis that the second window of APC is mediated by the activation of PPARγ. New Zealand White rabbits (n = 48) were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion. The animals received desflurane (1.0 minimal alveolar concentration), the PPARγ antagonist GW9662, as well as the combined application of both, respectively, 24 h prior to coronary artery occlusion. Infarct size was determined gravimetrically; tissue levels of 15-deoxy-(12,14)-prostaglandin J(2) (15d-PGJ(2)) and nitrite/nitrate (NO(x)), as well as PPAR DNA binding were measured using specific assays. Data are presented as means ± s.e.m. Desflurane led to a reduced myocardial infarct size (41.7 ± 2.5 versus 61.8 ± 2.8%, P < 0.05), accompanied by significantly increased PPAR DNA binding (289.9 ± 33 versus 102.9 ± 18 relative light units, P < 0.05), as well as elevated tissue levels of 15d-PGJ(2) (224.4 ± 10.2 versus 116.9 ± 14.2 pg ml(-1), P < 0.05) and NO(x) (14.9 ± 0.7 versus 5.4 ± 0.7 μm, P < 0.05). Pharmacological inhibition of PPARγ abolished these protective effects, resetting the infarct size (56.5 ± 2.9%), as well as PPAR DNA-binding activity (91.2 ± 31 relative light units) and NO(x) tissue levels (5.9 ± 0.9 μm) back to control levels. Desflurane governs a second window of APC by increasing the production of 15d-PGJ(2), subsequently activating PPARγ, resulting in a diminished myocardial infarct size by increasing the downstream availability of NO.

The authors tested the hypothesis that volatile anesthetic-induced preconditioning (APC) follows a similar time pattern as that described for ischemic preconditioning and that delayed APC is mediated by nitric oxide.A prospective randomized vehicle-controlled study.A university research laboratory.New Zealand white rabbits (n = 75).Rabbits were instrumented for the measurement of systemic hemodynamics and subjected to a 30-minute coronary artery occlusion (CAO) and 3 hours of reperfusion. Desflurane (1.0 minimum alveolar concentration) was administered for 30 minutes and was discontinued 0.5 hours, 2 hours, 3 hours, 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours before CAO, respectively. In 2 separate experimental groups, the nitric oxide synthase inhibitor N-omega-nitro-L-arginine (L-NA) was administered 72 hours after the administration of 0.0 or 1.0 minimum alveolar concentration of desflurane. The infarct size was determined gravimetrically. Data are mean +/- standard deviation.Desflurane significantly (p0.05) reduced the infarct size compared with the control (63% +/- 12%, n = 7) when administered 0.5 hours (35% +/- 5%, n = 7), 2 hours (35% +/- 9%, n = 7), 24 hours (31% +/- 8%, n = 7), 48 hours (30% +/- 11%, n = 6), and 72 hours (39% +/- 5%, n = 6) before CAO. However, when desflurane was administered 3 hours (53% +/- 9%, n = 7), 12 hours (71% +/- 6%, n = 7), or 96 hours (66% +/- 5%, n = 7) before CAO, the myocardial infarct size was not reduced. The second window (72 hours) of preconditioning was abolished by the NOS inhibitor L-NA (52% +/- 16%, n = 7). L-NA alone had no effect on infarct size (64% +/- 11%, n = 7).Desflurane induces a first (0.5-2 hours) and second window of preconditioning (24-72 hours) in the rabbit model of acute myocardial infarction. The second window of APC is mediated by nitric oxide.

The murine in vivo model of acute myocardial infarction is increasingly used to investigate anesthetic-induced preconditioning (APC) and postconditioning (APOST). However, in mice the potency of different volatile anesthetics to reduce myocardial infarct size (IS) has never been investigated systematically nor in a head to head comparison with regard to ischemic preconditioning (IPC) and postconditioning (IPOST). Male C57BL/6 mice were subjected to 45 min of coronary artery occlusion (CAO) and 180 min of reperfusion. To induce APC, 1.0 MAC isoflurane (ISO), sevoflurane (SEVO) or desflurane (DES) was administered 30 min prior to CAO for 15 min. In an additional group, ISO was administered 45 min prior to CAO for 30 min. To induce APOST, 1.0 MAC ISO, SEVO or DES was administered for 18 min starting 3 min prior to the end of CAO. IPC was induced by 3 or 6 cycles of 5 min ischemia/reperfusion, 40 or 60 min prior to CAO, respectively. IPOST was induced by 3 cycles of 30 sec reperfusion/ischemia at the beginning of reperfusion. Area at risk (AAR) and IS were determined with Evans Blue and TTC staining, respectively. IS (IS/AAR) was 50 +/- 4% (mean +/- SEM) in the control group and was significantly (*P < 0.05) reduced by 3x5 IPC (26 +/- 3%*), 6 x 5 IPC (26 +/- 4%*), IPOST (20 +/- 2%*), ISO APOST (19 +/- 1%*), SEVO APOST (15 +/- 1%*), DES APOST (14 +/- 2%*) and SEVO APC (27 +/- 6%*). ISO APC significantly reduced IS compared to control when administered 30 min (33 +/- 4%*), but not when administered 15 min (48 +/- 6%). DES APC significantly reduced IS compared to control and to SEVO APC (7 +/- 1%*). Within the paradigm of preconditioning, the potency of volatile anesthetics to reduce myocardial infarct size in mice significantly increases from ISO over SEVO to DES, whereas within the paradigm of postconditioning the potency of these volatile anesthetics to reduce myocardial infarct size in mice is similar.

Objective An optimal administration protocol to induce a maximal effect of anesthetic preconditioning has not been evaluated to date. In this study, desflurane preconditioning was characterized with respect to its threshold, dose dependency, and continuous versus repetitive application. Furthermore, the role of β 2 -adrenergic receptors in anesthetic preconditioning was tested. Design A randomized controlled study. Setting Laboratory study in a University hospital. Subjects New Zealand white rabbits in vivo. Interventions Systemic hemodynamics were continuously measured. Rabbits were subjected to 30 minutes of coronary artery occlusion and 3 hours of reperfusion. Animals received desflurane continuously for 30 minutes at 0.5, 1.0, or 1.5; desflurane for 90 minutes at 0.5 or 1.5 MAC; or repetitively for three 10-minute periods at 0.5, 1.0, or 1.5 MAC before coronary occlusion. The β 2 -adrenergic receptor blocker ICI 118,551 (0.2 mg/kg) or saline placebo was given in the absence or presence of 1.0 MAC desflurane. Myocardial infarct size was measured with triphenyltetrazolium staining. Measurements and Main Results Myocardial infarct size was 61% ± 5% in control experiments. Desflurane, administered continuously at 0.5 MAC for 30 minutes (52% ± 4%) or 90 minutes (56% ± 8%) had no effect, whereas 0.5 MAC of desflurane given repetitively reduced infarct size to 36% ± 7%. Desflurane administered continuously for 30 minutes at 1.0 or 1.5 MAC reduced infarct size to 35% ± 5% and 39% ± 4%, respectively. Repetitive application at 1.0 MAC (37% ± 6%) or 1.5 MAC (29% ± 4%) and continuous administration of 1.5 MAC for 90 minutes (32% ± 6%) did not result in further infarct size reduction. ICI 118,551 did not affect infarct size (53% ± 2%) but abolished desflurane preconditioning (51% ± 5%). Conclusion β 2 -Adrenergic receptors mediate desflurane-induced preconditioning. Desflurane-induced preconditioning has a threshold that can be lowered by repetitive administration.

Summary Background: GlideScope laryngoscopy provides a glottic view equal or superior compared to Macintosh laryngoscopy for endotracheal intubation in adult patients. Data evaluating GlideScope laryngoscopy in pediatric patients are lacking. This study compared intubation times of GlideScope laryngoscopy vs Macintosh laryngoscopy in pediatric patients. Methods: Sixty ASA I–III patients, aged 10 years or less, were included in this study. Prior to intubation, airway characteristics were measured, and all patients were given an airway class by a separate anesthesiologist using a Macintosh laryngoscope. Patients were then randomly assigned for endotracheal intubation using a Macintosh laryngoscope or the GlideScope, and intubation time was measured. All blades were investigated for blood traces as a surrogate of laryngeal injury. Results: Demographic data and airway characteristics were not statistically significant different between groups. GlideScope intubation time (14 ± 5 s) was not different from Macintosh intubation time (13 ± 5 s). Blood traces were not observed on Macintosh or GlideScope blades. Conclusion: The GlideScope video laryngoscope is equally suitable to facilitate orotracheal intubation in pediatric patients compared to the Macintosh laryngoscope with respect to intubation time and laryngeal trauma.

Optical laryngoscopes have been developed to facilitate difficult airway management. The Airtraq is a single-use device and the GlideScope is reusable. In this study, the Airtraq and the Glidescope were compared in 60 ASA I-III patients with tumours of the upper airway undergoing direct endoscopic microlaryngoscopy. Patients were randomly assigned to the Airtraq or the Glidescope group and the Cormack and Lehane grade was assessed by Macintosh laryngoscopy prior to tracheal intubation. There were no differences in tracheal intubation success rates or duration of intubation attempts between both devices. The Cormack and Lehane grade was improved in 77% and 82% of cases in the Airtraq and Glidescope group, respectively. Blood traces on the device and traumatic pharyngeal lesions were found more frequently in the Airtraq group. The Airtraq and Glidescope laryngoscopes are valuable tools for the management of patients with potentially difficult airways with the Glidescope appearing to be less traumatic.

Improving perioperative efficiency and tightly maintaining the patient's homeostasis in order to improve rehabilitation and well-being are key factors in the increasing popularity of fast-track recovery programs. Although the pharmacological contribution should not be overestimated, the use of up-to-date pharmacological agents with predictable duration of action and minimal side effects is mandatory to allow for a fast and gentle recovery process.A literature review of about 160 peer-reviewed publications provides the basis for this review of pharmacological interventions for optimizing recovery following anesthesia.The choice of anesthetic technique and pharmacological agents should be tailored to the needs of the patient as well as the type of procedure being performed as fast-track surgery. The universally applicable goals valid for every class of intervention are that they should be easy to use, have minimal side effects, maintain homeostasis, allow for a predictable on- and offset, and give minimal impairment of recovery and function.The pivotal role played by the anesthesiologist in facilitating the recovery process following surgical procedures has assumed increased importance in the concept of enhanced recovery programs. Although the interdisciplinary approach common to all parties involved (surgeons, anesthesiologists, nurses, physiotherapists) is the true enabler of fast-track surgery, the choice of anesthetic drugs and concomitant medication can all influence the ability to fast-track patients after surgery and should therefore considered mandatory in fast-track programs.

Cardioprotection by ischemic preconditioning (IP) remains an area of intense investigation. To further elucidate its molecular basis, the use of transgenic mice seems critical. Due to technical difficulty associated with performing cardiac IP in mice, we developed an in situ model for cardiac IP using a hanging-weight system for coronary artery occlusion. This technique has the major advantage of eliminating the necessity of intermittently occluding the coronary artery with a knotted suture. To systematically evaluate this model, we first demonstrated correlation of ischemia times (10–60 min) with infarct sizes [3.5 ± 1.3 to 42 ± 5.2% area at risk (AAR), Evan’s blue/triphenyltetrazolium chloride staining]. IP (4 × 5 min) and cold ischemia (27°C) reduced infarct size by 69 ± 6.7% and 84 ± 4.2%, respectively ( n = 6, P < 0.01). In contrast, lower numbers of IP cycles did not alter infarct size. However, infarct sizes were distinctively different in mice from different genetic backgrounds. In addition to infarct staining, we tested cardiac troponin I (cTnI) as marker of myocardial infarction in this model. In fact, plasma levels of cTnI were significantly lower in IP-treated mice and closely correlated with infarct sizes ( R2 = 0.8). To demonstrate transcriptional consequences of cardiac IP, we isolated total RNA from the AAR and showed repression of the equilibrative nucleoside transporters 1–4 by IP in this model. Taken together, this study demonstrates highly reproducible infarct sizes and cardiac protection by IP, thus minimizing the variability associated with knot-based coronary occlusion models. Further studies on cardiac IP using transgenic mice may consider this technique.

Background Volatile anesthetics induce myocardial preconditioning through a signal transduction pathway that is remarkably similar to that observed during ischemic preconditioning. Nitric oxide-dependent signaling plays an important role in anesthetic and ischemic preconditioning. Therefore, the authors tested the hypothesis that desflurane-induced preconditioning is mediated by nitric oxide. Methods Barbiturate-anesthetized rabbits were instrumented for measurement of hemodynamics. All rabbits were subjected to 30-min coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size was assessed with triphenyltetrazolium chloride staining. Myocardial nitric oxide synthase activity was assessed with a [H]L-arginine-conversion assay. Rabbits were randomized to five separate experimental groups. They received 0.0 or 1.0 minimum alveolar concentration desflurane for 30 min, which was discontinued 30 min before ischemia in the absence or presence of the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA). L-NA was given either 20 min before or 10 min after desflurane administration, respectively. Data are mean +/- SEM. Results Infarct size was 56 +/- 8% in control experiments. Desflurane significantly (P < 0.05) reduced infarct size to 35 +/- 4%. Preconditioning by desflurane was totally blocked by administration of L-NA either during or after desflurane inhalation (58 +/- 4 and 59 +/- 9%, respectively). L-NA alone had no effect on infarct size (56 +/- 7%). Nitric oxide synthase activity was significantly (P < 0.05) increased by desflurane. Conclusion The results demonstrate that desflurane-induced preconditioning markedly reduced myocardial infarct size. This beneficial effect was blocked by the nitric oxide synthase inhibitor L-NA either during or after desflurane-administration. These data suggest that early desflurane-induced preconditioning is mediated by nitric oxide.

Nitric oxide synthases (NOSs) mediate the first window of anesthetic-induced preconditioning (APC). The authors tested the hypothesis that endothelial NOS (eNOS) mediates the first window and inducible NOS (iNOS) mediates the second window of APC.Randomized, prospective, blinded laboratory investigation.Experimental laboratory.Mice.Mice were subjected to a 45-minute coronary artery occlusion (CAO) and a 180-minute reperfusion. C57BL/6 mice received desflurane, 1.0 minimum alveolar concentration, for 30 minutes or 12, 24, 48, or 96 hours before CAO. In eNOS(-/-) and iNOS(-/-) mice, desflurane was given 30 minutes and 48 hours before CAO. In the control groups, no desflurane was administered. Myocardial infarct size (IS) was determined after staining with Evans blue and triphenyltetrazolium chloride.The second window of APC was detectable at 48 hours but not at 12, 24, and 96 hours after preconditioning. In the control groups, IS was not different among the wild-type (50 ± 10%), eNOS(-/-) (52 ± 14%), and iNOS(-/-) (46 ± 10%) mice. The IS decreased significantly (p0.05) when desflurane was administered 30 minutes (10 ± 6%) or 48 hours (16 ± 7%) before CAO in wild-type mice, 48 hours (21 ± 13%) before CAO in eNOS(-/-) mice, and 30 minutes (13 ± 6%) before CAO in iNOS(-/-) mice. Desflurane given 30 minutes before CAO in eNOS(-/-) mice (60 ± 10%) and 48 hours before CAO in iNOS(-/-) mice (48 ± 21%) did not decrease the IS significantly compared with controls.Endothelial NOS and iNOS work independently to mediate the first and second windows of APC, respectively. Endothelial NOS is not necessary to trigger the second window of APC.

The authors tested the hypothesis that ischemic and desflurane-induced preconditioning are blocked by propofol.A prospective, randomized, vehicle-controlled study.A university research laboratory.New Zealand white rabbits (n = 52).Pentobarbital-anesthetized rabbits were subjected to 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. Rabbits received 0.0 (control) or 1.0 minimum alveolar concentration of desflurane (30 minutes' duration and a 30-minute memory period) or ischemic preconditioning (5 minutes of ischemia and a 30-minute memory period) in the absence or presence of propofol (10 mg/kg/h intravenously) or its vehicle (10% Intralipid emulsion; B Braun, Melsungen, Germany). The myocardial infarct size was measured with triphenyltetrazolium staining. Statistical analysis was performed with 1-way and 2-way analysis of variance when appropriate, followed by a post hoc Duncan test. Data are mean ± standard deviation.Myocardial infarct size was 56% ± 8% in control animals (n = 7). Desflurane significantly (p0.05) reduced the infarct size to 37% ± 6% (n = 7). Desflurane-induced preconditioning was blocked by propofol (65% ± 10%, n = 7) but not by its vehicle (45% ± 11%, n = 5). Propofol and its vehicle alone had no effect on the infarct size (62% ± 8% [n = 6] and 58% ± 3% [n=5], respectively). Ischemic preconditioning reduced infarct size in the absence or presence of propofol to 24% ± 7% (n = 7) and 29% ± 12% (n = 6).Desflurane-induced preconditioning markedly reduced infarct size and was blocked by propofol, whereas ischemic preconditioning was not blocked by propofol. The results suggest an important interference between propofol and anesthetic-induced preconditioning and might explain some contradictory findings in studies in humans.

Background Ischemic preconditioning (IPC) and anesthetic-induced preconditioning against myocardial infarction are mediated via protein kinase B. Pim-1 kinase acts downstream of protein kinase B and was recently shown to regulate cardiomyocyte survival. The authors tested the hypothesis that IPC and anesthetic-induced preconditioning are mediated by Pim-1 kinase. Methods Pentobarbital-anesthetized male C57Black/6 mice were subjected to 45 min of coronary artery occlusion and 3 h of reperfusion. Animals received no intervention, Pim-1 kinase inhibitor II (10 microg/g intraperitoneally), its vehicle dimethyl sulfoxide (10 microl/g intraperitoneally), or 1.0 minimum alveolar concentration desflurane alone or in combination with Pim-1 kinase inhibitor II (10 microg/g intraperitoneally). IPC was induced by three cycles of 5 min ischemia-reperfusion each, and animals received IPC either alone or in combination with Pim-1 kinase inhibitor II (10 microg/g intraperitoneally). Infarct size was determined with triphenyltetrazolium chloride, and area at risk was determined with Evans blue (Sigma-Aldrich, Taufkirchen, Germany). Protein expression of Pim-1 kinase, Bad, phospho-Bad, and cytosolic content of cytochrome c were measured using Western immunoblotting. Results Infarct size in the control group was 47 + or - 2%. Pim-1 kinase inhibitor II (44 + or - 2%) had no effect on infarct size. Desflurane (17 + or - 3%) and IPC (19 + or - 2%) significantly reduced infarct size compared with control (both P < 0.05 vs. control). Blockade of Pim-1 kinase completely abrogated desflurane-induced preconditioning (43 + or - 3%), whereas IPC (35 + or - 3%) was blocked partially. Desflurane tended to reduce cytosolic content of cytochrome c, which was abrogated by Pim-1 kinase inhibitor II. Conclusion These data suggest that Pim-1 kinase mediates at least in part desflurane-induced preconditioning and IPC against myocardial infarction in mice.

Myocardial ischemia is accompanied by a rapid activation of adenosine-monophosphate-activated protein kinase (AMPK). However, it is unclear whether this represents a potentially beneficial or detrimental event in the course of ischemic injury. The role of AMPK activation in the cardioprotective setting of desflurane-induced preconditioning has not been investigated to date. Hence, the current study was undertaken to address the role of AMPK activation during desflurane-induced preconditioning in vivo.A prospective randomized vehicle-controlled study.A university research laboratory.Male New Zealand white rabbits (n = 44).The animals were subjected to a 30-minute coronary artery occlusion (CAO) followed by 3 hours of reperfusion. Desflurane (1.0 minimum alveolar concentration) was administered for 30 minutes and discontinued 30 minutes prior to CAO. Different groups of animals received the AMPK activator, 5-aminoimidazole-4-carboxamide-1-b-riboside (AICAR), alone or in combination with desflurane. Infarct size was determined gravimetrically; AMPK activity and myocardial glycogen content were measured using specific assays. Phosphorylation of the AMPK substrate, acetyl-CoA carboxylase, was assessed by immunoblotting. Data are mean ± standard error of the mean.Desflurane significantly reduced the myocardial infarct size (36.7 ± 1.9%, p0.05) compared with the control group (61.6% ± 3.0%), concomitant with increased myocardial tissue levels of glycogen (2.09 ± 0.07 μg, p0.05). Activation of the AMPK by AICAR alone did not protect against ischemic injury (65% ± 3.3), but did abolish the cardioprotection elicited by desflurane (61.8% ± 4.2%) at the same time as increasing myocardial glycogen consumption (1.42 ± 0.15 μg/mL).The results obtained show that the pharmacologic activation of AMPK abolishes cardioprotection elicited by desflurane.

The authors tested the hypothesis that desflurane-induced cardioprotection depends on the timing of application and whether desflurane-induced postconditioning is mediated by nitric oxide.A prospective randomized vehicle-controlled study.A university research laboratory.New Zealand White rabbits (N = 56).Rabbits were instrumented and subjected to a 30-minute coronary artery occlusion (CAO) and 3 hours of reperfusion. Animals were randomized to 8 groups (n = 7) and received 0.0 or 1.0 minimum alveolar concentration desflurane for 30 minutes before CAO (PRE), during CAO (ISCH), after CAO (POST), before and after CAO (PRE + POST), or continuously for 90 minutes starting 30 minutes before CAO (PRE + ISCH + POST). In 2 separate experimental groups, the nitric oxide synthase inhibitor N-omega-nitro-L-arginine (L-NA) was administered before reperfusion in the presence or absence of desflurane. Data are mean +/- standard deviation.Infarct size was 68% +/- 14% in control experiments. Desflurane significantly (p0.05) reduced infarct size in the PRE (43% +/- 9%) and POST groups (49% +/- 12%) but not in the ISCH group (69% +/- 9%). The PRE + ISCH + POST and PRE + POST groups produced similar reductions in infarct size to 47% +/- 12% and 43% +/- 9%, respectively. L-NA alone had no effect on infarct size (61% +/- 9%) but blocked postconditioning completely (L-NA + POST, 68% +/- 10%).Desflurane induces pre- and postconditioning but does not confer cardioprotection during ischemia in rabbits. The combination of pre- and postconditioning or continuous application does not provide additional cardioprotection. Furthermore, desflurane-induced postconditioning is mediated by nitric oxide.

Almost 50 % of all patients that are evaluated preoperatively by an anesthesiologist are receiving concurrent medication. Many of the prescribed drugs can be omitted during the perioperative period. However, perioperative cessation of certain drug therapies may cause decompensation of primarily compensated diseases. After reading this CME article, the reader should be able to decide whether any cardiovascular, pulmonary or antidiabetic drug therapy should be continued or ceased during the perioperative period, respectively.

The murine in vivo model of acute myocardial infarction is increasingly used to study signal transduction pathways. However, methodological details of this model are rarely published, and durations of ischemia and reperfusion (REP) time vary considerably among different laboratories. In this study, we tested the hypothesis that infarct size (IS) is dependent on both duration of ischemia and REP time. Pentobarbital-anesthetized male C57BL/6 mice were intubated, mechanically ventilated, and instrumented for continuous monitoring of mean arterial blood pressure and heart rate. After left fourth thoracotomy, the left anterior descending coronary artery was ligated. Mice were randomly assigned to receive 30, 45, or 60 mins of coronary artery occlusion (CAO) and 120, 180, or 240 mins of REP, respectively. IS was determined with triphenyltetrazolium chloride and area at risk (AAR) with Evans blue, respectively. Arterial blood gas analysis and hemodynamics were not different among groups. Prolongation of CAO from 30 to 60 mins significantly (* P < 0.05) increased IS from 18% ± 5% to 69% ± 3%*, from 20% ± 2% to 69% ± 6%* and from 42% ± 10% to 75% ± 2%* after 120, 180, and 240 mins REP, respectively. Moreover, IS was increased from 18% ± 5% to 42% ± 10%* (30 mins CAO) and from 40% ± 3% to 72% ± 6%* (45 mins CAO) when REP time was prolonged from 120 to 240 mins. IS was not increased when REP was prolonged from 120 to 240 mins at 60 mins CAO (69% ± 3% vs. 75% ± 2%). In the present study, we describe important methodological aspects of the murine in vivo model of acute myocardial infarction and provide evidence that, in this model, IS depends both on duration of ischemia and on REP time.

High-frequency oscillatory ventilation (HFOV) may reduce ventilator-induced lung injury in experimental neonatal respiratory distress. However, these data permit no conclusions for large animals or adult patients with acute respiratory distress syndrome (ARDS), because in neonates higher frequencies and lower amplitudes can be used, resulting in lower tidal volumes (VT) and airway pressures. The aim of this study was to compare gas exchange, lung histopathology and inflammatory cytokine expression during lung-protective pressure-controlled ventilation (PCV) and HFOV in a long-term large-animal model of ARDS. Prospective, randomized, controlled pilot study. University animal laboratory. Sixteen female pigs (55.3 ± 3.9 kg). After induction of ARDS by repeated lavage, the animals were randomly assigned to PCV (VT = 6 ml/kg) and HFOV (6 Hz). After lung injury, a standardised lung recruitment was performed in both groups, and ventilation was continued for 24 h. Measurements and results: After lung recruitment sustained improvements in the oxygenation index were observed in both groups. The mean airway pressure (mPaw) was significantly lower in the HFOV group during the experiment ( p