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ZusammenfassungEtwa ein Drittel aller Patienten, die sich einem operativen Eingriff unterziehen, nehmen chronisch Psychopharmaka ein. Neben Depressionen und Psychosen stellen chronische Schmerzen sowie Angst- und Panikstörungen die häufigsten Indikationen dar. In den vergangenen 30 Jahren stieg die Häufigkeit der Verordnung von Psychopharmaka um das 7-Fache. Fast alle Psychopharmaka interagieren mit Medikamenten, die perioperativ häufig gegeben werden, beispielsweise mit 5-HT3-Antagonisten, Sympathomimetika oder Opioiden. Einige der Medikamente weisen eine enge therapeutische Breite auf und nicht alle Medikamente können perioperativ pausiert werden. Im Rahmen der präoperativen Risikoevaluation ist daher eine Prüfung im Einzelfall notwendig. Der Anästhesist muss zudem bei Gabe bestimmter Medikamente während der Narkose besondere Vorsicht walten lassen oder ganz auf diese verzichten.Bei der Therapie vieler neurologischer Erkrankungen stellen Medikamente die zentrale Säule dar. Häufig begegnen dem Anästhesisten Patienten mit einer Epilepsie, mit Morbus Parkinson oder mit einer Myasthenia gravis, die eine entsprechende medikamentöse Therapie erhalten. Das perioperative Pausieren der Medikamente lässt zumeist eine Befundverschlechterung der neurologischen Grunderkrankung befürchten. Auf die möglichst rasche postoperative Einnahme der Dauermedikation ist daher besonderer Wert zu legen.

More than a third of all patients undergoing surgery take psychotropic agents on a regular basis. Aside from classical indications like depression and psychosis these drugs are often prescribed for treatment of pain, anxiety and panic disorder. Over the last 30 years the frequency of prescription of psychotropic drugs increased by seven times. Of note, drug interactions of psychoactive medications and anaesthetic agents are common, and the therapeutic range is narrow. Since not all of these agents can be stopped uncritically, careful assessment of risks and benefits is obligatory. The anaesthesiologist has to take special care or avoid the use of certain medications.Medical treatment is crucial for the treatment of several neurological disorders. Frequently, anaesthesiologists are faced with common diseases like seizure disorders, Parkinson's disease and Myasthenia gravis. Perioperative withdrawal of specific medication implies the risk of recurrence of the neurological symptoms. Therefore, these drugs should be continued postoperatively as soon as possible.

Diabetes is a major risk factor for cardiovascular disease, affecting both endothelial and smooth muscle cells. Store-operated Ca2+ channels (SOCCs) have been implicated in many diabetic complications. Vascular dysfunction is common in patients with diabetes, but the role of SOCCs in diabetic vasculopathy is still unclear. Our research aimed to investigate the effects of high glucose (HG) on store-operated Ca2+ entry (SOCE) in small arteries. Small mesenteric arteries from type 2 diabetic Zucker fatty rats (ZDF) versus their non-diabetic controls (Zucker lean, ZL) were examined in a pressurized myograph. Vascular smooth muscle cells (VSMC) were isolated and intracellular Ca2+ was measured (Fura 2-AM). A specific protocol to deplete intracellular Ca2+ stores and thereby open SOCCs, as well as pharmacological SOCE inhibitors (SKF-96365, BTP-2), were used to artificially activate and inhibit SOCE, respectively. High glucose (40 mmol/L) relaxed arteries in a SKF-sensitive manner. Diabetic arteries exhibited reduced HG-induced relaxation, as well as reduced contraction after Ca2+ replenishment. Further, the rise in intracellular Ca2+ on account of SOCE is diminished in diabetic versus non-diabetic VSMCs and was insensitive to HG in diabetic VSMCs. The expression of SOCC proteins was measured, detecting a downregulation of Orai1 in diabetes. In conclusion, diabetes leads to a reduction of SOCE and SOCE-induced contraction, which is unresponsive to HG-mediated inhibition. The reduced expression of Orai1 in diabetic arteries could account for the observed reduction in SOCE.

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.

Background Bleeding is a major adverse effect of veno-venous extracorporeal membrane oxygenation (vvECMO) therapy in surgical patients. This study retrospectively describes the amount of transfused packed red blood cells (PRBC) and coagulation parameters of patients requiring surgery during vvECMO therapy. Methods We included patients who underwent at least one surgical procedure during vvECMO therapy and analyzed hemoglobin levels, coagulation parameters, blood gas parameters and transfused blood products. Patients with perioperative transfusion of less than two PRBC during the perioperative period (group A) were compared to those who were given two or more PRBCs (group B). Results Seventy-three patients (group A: 42 patients, group B: 31 patients) were included. Activated PTT (54.7 vs. 56.2 sec), Quick test (61.5% vs. 60.0%), Platelet count (91 vs 72 / nL, P=0.322) and mortality (40.5 vs. 45.2%; P=0.689) were not different between both groups. Fibrinogen was significantly decreased in group B (245 mg/dL) compared to group A (353 mg/dL; P=0.004). Conclusions In patients requiring surgery during vvECMO therapy with perioperative transfusion of two or more PRBCs preoperative fibrinogen levels were significantly reduced compared to patients with transfusion of less than two PRBCs. No other analyzed lab value showed any predictive qualities in terms of bleeding.

Diabetes is a major risk factor for cardiovascular disease, affecting both endothelial and smooth muscle cells. Store-operated Ca

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.

Background Mutations in NFKB1(nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) are associated with a variety of clinical symptoms, including lymphadenopathy, splenomegaly, hepatomegaly, autoimmune haemolytic anaemia, arthralgia, recurrent respiratory tract infections and post-operative necrotizing cellulitis. Case presentation We describe a case of a 47-year-old man, who presented with deep necrotizing cellulitis after incision of a submucous abscess by a dentist. Surgical intervention led to a massive progress. Pyoderma gangraenosum (PG) was diagnosed clinically and confirmed histopathologically. High dose corticosteroids and intravenous immunoglobulins (IVIG) improved wound healing dramatically. Until now, immune mediated inflammation events not only affected the skin, but also multiple inner organs, i.e. the heart, lungs and gut. Sequencing of all coding exons of NFKB1 revealed a heterozygous 1bp deletion in exon 23 predicting a frameshift starting at codon Ala891 and resulting in a subsequent stop codon at position 6 in the new reading frame: NM_003998.4: c.2671del; p.(Ala891Glnfs*6) Acute episodes were always successfully treated with corticosteroids, IVIG and concomitant antibiotics. To prevent further exacerbations, the patient receives IVIG once a month, low-dose corticosteroids and methotrexate. Conclusion This is the first case of a patient with recurrent necrotizing cellulitis and immune mediated multi-organ involvement (heart, lungs, intestine) carrying the novel frameshift mutation c.2671del (p.Ala891Glnfs*6) in NFKB1 effectively treated with IVIG, low-dose corticosteroids and methotrexate.

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.

Ein betrachtlicher Teil der Patienten, die sich dem Anasthesiologen im Rahmen der Pramedikationsvisite vorstellen, nimmt regelmasig Medikamente ein. Neben Arzneistoffen fur kardiovaskulare, pulmonale und metabolische Erkrankungen handelt es sich vielfach auch um antidepressiv, seltener um antipsychotisch wirksame Substanzen. Einige dieser Substanzen interagieren mit Anasthetika. Daher wird der Anasthesiologe im Rahmen der Pramedikationsvisite nicht selten mit der Frage nach der perioperativen Modifikation der psychiatrischen Dauermedikation konfrontiert. Weil das abrupte Absetzen antidepressiv oder antipsychotisch wirksamer Substanzen zum Wiederauftreten entsprechender Symptome und zu einem Entzugssyndrom fuhren kann, empfiehlt es sich grundsatzlich, die Entscheidung uber die perioperative Modifikation dieser Arzneitherapie gemeinsam mit dem behandelnden psychiatrischen Kollegen zu fallen. Soll die psychiatrische Medikation abgesetzt werden, ist auch der indikationsstellende Chirurg in die Risiko-Nutzen-Abwagung einzubeziehen, da der operative Eingriff aufgrund der langen Halbwertszeiten meist um mehrere Tage zu verschieben ist. Da in der Literatur keine prospektiv-randomisiert erhobenen Daten zur perioperativen Verordnung psychiatrischer Arzneistoffe vorliegen, muss sich diese Risiko-Nutzen-Abwagung neben physiologischen und pharmakologischen Grunduberlegungen auf publizierte Fallberichte und Expertenmeinungen berufen. Aus Anlass einer Leseranfrage an AINS zur perioperativen Verordnung von Opipramol werden nachfolgend die verfugbaren Daten zur perioperativen Verordnung bestimmter psychiatrischer Arzneimittel zusammengefasst, um dem Leser eine Entscheidungshilfe fur das Absetzen oder Weiterverordnen der praoperativen Dauermedikation bei psychiatrischen Erkrankungen an die Hand zu geben.

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.

Background Anesthetic preconditioning is mediated by beta-adrenergic signaling. This study was designed to elucidate the role of beta-adrenergic signaling in desflurane-induced postconditioning. Methods Pentobarbital-anesthetized New Zealand White rabbits were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive vehicle (control), 1.0 minimum alveolar concentration of desflurane, esmolol (30 mg x kg(-1) x h(-1)) for the initial 30 min of reperfusion or throughout reperfusion, the beta2-adrenergic receptor blocker ICI 118,551 (0.2 mg/kg), the protein kinase A inhibitor H-89 (250 microg/kg), or the calcium/calmodulin-dependent protein kinase II inhibitor KN-93 (300 microg/kg) in the presence or absence of desflurane. Protein expression of protein kinase B, calcium/calmodulin-dependent protein kinase II, and phospholamban was measured by Western immunoblotting. Myocardial infarct size was assessed by triphenyltetrazolium staining. Results Infarct size was 57 +/- 5% in control. Desflurane postconditioning reduced infarct size to 36 +/- 5%. Esmolol given during the initial 30 min of reperfusion had no effect on infarct size (54 +/- 4%) but blocked desflurane-induced postconditioning (58 +/- 5%), whereas esmolol administered throughout reperfusion reduced infarct size in the absence or presence of desflurane to 42 +/- 6% and 41 +/- 7%, respectively. ICI 118,551 and KN-93 did not affect infarct size (62 +/- 4% and 62 +/- 6%, respectively) but abolished desflurane-induced postconditioning (57 +/- 5% and 64 +/- 3%, respectively). H-89 decreased infarct size in the absence (36 +/- 5%) or presence (33 +/- 5%) of desflurane. Conclusions Desflurane-induced postconditioning is mediated by beta-adrenergic signaling. However, beta-adrenergic signaling displays a differential role in cardioprotection during reperfusion.

Background Anesthetic preconditioning is mediated by beta- adrenergic signaling. This study tested the hypotheses that desflurane-induced preconditioning is dose-dependently blocked by metoprolol and mediated by calcium/calmodulin-dependent protein kinase II (CaMK II). Methods Pentobarbital-anesthetized New Zealand White rabbits were instrumented for measurement of systemic hemodynamics and subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion. Rabbits were assigned to receive vehicle (control), 0.2, 1.0, 1.75, or 2.5 mg/kg metoprolol for 30 min, or the CaMK II inhibitor KN-93 in the absence or presence of 1.0 minimum alveolar concentration desflurane. Protein expression of CaMK II, phospholamban, and phospho-phospholamban was measured by Western blotting. Myocardial infarct size and area at risk were measured with triphenyltetrazolium staining and patent blue, respectively. Results Baseline hemodynamics were not different among groups. Infarct size was 60 +/- 3% in control and significantly (* P < 0.05) decreased to 33 +/- 2%* by desflurane. The CaMK II inhibitor KN-93 did not affect infarct size (55 +/- 4%) but blocked desflurane-induced preconditioning (57 +/- 3%). Metoprolol at 0.2 and 1.0 mg/kg had no effect on infarct size (55 +/- 3% and 53 +/-3%), whereas metoprolol at 1.75 and 2.5 mg/kg reduced infarct size to 48 +/- 4%* and 39 +/- 5%*, respectively. Desflurane-induced preconditioning was attenuated by metoprolol at 0.2 mg/kg, leading to an infarct size of 46 +/- 5%*, and was completely abolished by metoprolol at 1.0, 1.75, and 2.5 mg/kg, resulting in infarct sizes of 51 +/- 3%, 52 +/- 3%, and 55 +/- 3%, respectively. Conclusions Desflurane-induced preconditioning is dose-dependently blocked by metoprolol and mediated by CaMK II.

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.

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.

Background Late ischemic preconditioning is mediated via nuclear transcription factor signal transducer and activator of transcription 3 (STAT3). Pim-1 kinase reduces infarct size in cardiomyocytes and is regulated by STAT3. We tested the hypothesis that late desflurane-induced preconditioning (DES-SWOP) is mediated via STAT3 and Pim-1. Methods After institutional approval, pentobarbital-anesthetized male C57BL/6 mice were subjected to 45 min coronary artery occlusion (CAO) and 3 h reperfusion. Control animals received no additional intervention. Desflurane was administered 48 h before CAO either alone or in combination with the janus kinase/STAT3 inhibitor AG-490 (40 μg/g i.p., 20 min before desflurane administration) or the Pim-1 kinase inhibitor II (PIM-Inh.II, 10 μg/g i.p., 15 min before CAO). Infarct size (IS) and area at risk were determined with triphenyltetrazolium chloride and Evans blue, respectively. Additionally, cytosolic and nuclear fractions were separated at two different time points and expression of STAT3, phospho-STAT3Ser727, phospho-STAT3Tyr705, Pim-1, Bad and phospho-BadSer112 were determined by Western Blot analysis. Data were analyzed with one-way or two-way ANOVA and post hoc Duncan test and are presented as mean ± SEM. Results IS was 47 ± 2% (n = 7–8 per group) in control animals (CON). DES-SWOP reduced myocardial infarct size to 23 ± 4%* (*P

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.

Background Anesthetic and ischemic preconditioning share similar signal transduction pathways. The authors tested the hypothesis that the beta1-adrenergic signal transduction pathway mediates anesthetic and ischemic preconditioning in vivo. Methods Pentobarbital-anesthetized (30 mg/kg) rabbits (n = 96) were instrumented for measurement of systemic hemodynamics and subjected to 30 min of coronary artery occlusion and 3 h of reperfusion. Sixty minutes before occlusion, vehicle (control), 1.0 minimum alveolar concentration desflurane, or sevoflurane, and esmolol (30.0 mg x kg(-1) x h(-1)) were administered for 30 min, respectively. Administration of a single 5-min cycle of ischemic preconditioning was instituted 35 min before coronary artery occlusion. In separate groups, the selective blocker esmolol or the protein kinase A inhibitor H-89 (250 microg/kg) was given alone and in combination with desflurane, sevoflurane, and ischemic preconditioning. Results Baseline hemodynamics and area at risk were not significantly different between groups. Myocardial infarct size (triphenyltetrazolium staining) as a percentage of area at risk was 61 +/- 4% in control. Desflurane, sevoflurane, and ischemic preconditioning reduced infarct size to 34 +/- 2, 36 +/- 5, and 23 +/- 3%, respectively. Esmolol did not alter myocardial infarct size (65 +/- 5%) but abolished the protective effects of desflurane and sevoflurane (57 +/- 4 and 52 +/- 4%, respectively) and attenuated ischemic preconditioning (40 +/- 4%). H-89 did not alter infarct size (60 +/- 4%) but abolished preconditioning by desflurane (57 +/- 5%) and sevoflurane (61 +/- 1%). Ischemic preconditioning (24 +/- 7%) was not affected by H-89. Conclusions The results demonstrate that anesthetic preconditioning is mediated by the beta1-adrenergic pathway, whereas this pathway is not essential for ischemic preconditioning. These results indicate important differences in the mechanisms of anesthetic and ischemic preconditioning.

The two small heat shock proteins (sHSPs), alphaB-crystallin and HSPB2, have been shown to translocate within a few minutes of cardiac ischemia from the cytosol to myofibrils; and it has been suggested that their chaperone-like properties might protect myofibrillar proteins from unfolding or aggregation during stress conditions. Further evidence of an important role for HSPs in muscle function is provided by the fact that mutations of the alphaB-crystallin gene cause myopathy and cardiomyopathy. In the present study, we subjected isolated papillary muscles of alphaB-crystallin/HSPB2-deficient mice to simulated ischemia and reperfusion. During ischemia in alphaB-crystallin/HSPB2-deficient muscles, the development of contracture started earlier and reached a higher value compared to the wildtype mice. The recovery of contracture of alphaB-crystallin/HSPB2-deficient muscles was also attenuated during the simulated reperfusion period. However, twitch force was not significantly altered at any time of the experiment. This suggests that during ischemic insults, alphaB-crystallin/HSPB2 may not be important for the contraction process itself, but rather serve to maintain muscular elasticity.

Cardiac physiology of the mouse is becoming increasingly important because the mouse is the mammalian model animal of choice for genetic modifications. However, mouse cardiac muscle is still poorly characterized under physiological conditions and inconsistent results have been published in the literature regarding mechanical activity especially the force-frequency relationship in isolated mouse muscle preparations. In this study we investigated systematically several mechanical parameters of isolated mouse papillary muscle such as force-frequency relation, twitch force, time to peak tension, relaxation time and post-rest potentiation at different experimental conditions. Extracellular calcium concentration ([Ca2+]) was varied between 1.0 and 5.0 mM, temperature between 27 degrees C and 37 degrees C and force measurements were performed under isometric as well as auxotonic conditions. The mechanical activity of muscle preparations was found to be strongly dependent on [Ca2+] and temperature and slightly on contraction type. At low temperature and low [Ca2+] the force-frequency relation was strongly positive whereas at high temperature and high calcium it turned negative. The results of this study demonstrate a flat force-frequency relation in mouse papillary muscle at physiological conditions (37 degrees C, [Ca2+] of 1.5 mM) and provide a reliable experimental basis for comparative studies with genetically altered mice.

Apart from cardiovascular, pulmonary and metabolic drugs, many patients scheduled for surgery are taking antidepressive or antipsychotic drugs. Some of these psychiatric drugs may interfere with anesthetics. The anesthesiologist has to decide whether or not to continue the psychiatric medication during the perioperative period. Since the discontinuation of psychiatric drugs may lead to withdrawal syndromes, the decision should be made in accordance with the attending psychiatrist. Should the discontinuation of any psychiatric drug be recommended, it may be prudent to involve the attending surgeon in order to postpone the procedure, since the modification of psychiatric drugs may take several days.Prospective randomized data about the perioperative modification of psychiatric drugs are scarce. Thus, recommendations in this regard must rely on physiological and pharmacological principles, case reports and published expert opinions. In this article we use the available data to answer the question of a journal reader regarding the perioperative modification of Opipramol therapy for a 59-year-old patient scheduled for elective shoulder surgery.

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.

Desflurane (DES)-induced preconditioning is mediated by large-conductance calcium-activated potassium channels (BK(Ca)). Whether BK(Ca) are involved in anaesthetic-induced post-conditioning is unknown. We tested the hypothesis that DES-induced post-conditioning is mediated by BK(Ca) upstream of the mitochondrial permeability transition pore (mPTP).Pentobarbital-anaesthetized male C57Black/6 mice were subjected to 45 min coronary artery occlusion (CAO) and 3 h reperfusion. Animals received either no intervention or dimethylsulphoxide (DMSO, 10 µl g(-1)). DES (1.0 MAC, 7.5 vol%) was administered for 18 min, starting 3 min before the end of CAO. The following agents were given either alone or in combination with DES: the BK(Ca) activator NS1619 (1 µg g(-1)), the BK(Ca) inhibitor iberiotoxin (IbTx, 0.05 µg g(-1)), the mPTP opener atractyloside (ATRA, 25 µg g(-1)), and the mPTP inhibitor cyclosporine A (CYC A, 10 µg g(-1)). Infarct size (IS) was determined with triphenyltetrazolium chloride and the area at risk with Evans Blue, respectively.IS in control animals was 48(6)%. Neither DMSO, IbTx nor ATRA affected myocardial IS. DES alone or NS1619 alone or the combination reduced IS (P0.05), CYC A alone or in combination with IbTx or DES also reduced IS (P0.05). DES-induced reduction of myocardial IS was completely abolished by IbTx and was partially blocked by ATRA and ATRA partially blocked IS reduction by NS1619.These data suggest that DES-induced post-conditioning against myocardial infarction is mediated by BK(Ca) and mPTP. Cardioprotection by BK(Ca) activator NS1619 might occur, at least in part, independently of mPTP.

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

Remote ischemic preconditioning (remote IPC) elicits a protective cardiac phenotype against myocardial ischemic injury. The remote stimulus has been hypothesized to act on major signaling pathways; however, its molecular targets remain largely undefined. We hypothesized that remote IPC exerts its effects by activating the peroxisome-proliferator-activated receptors (PPARs) α and γ, which have been previously implicated in cardioprotective signaling. Male New Zealand white rabbits ( n = 78) were subjected to a 30-min coronary artery occlusion followed by three hours of reperfusion. Three cycles of remote IPC consisting of 10-min renal ischemia/reperfusion were performed. The animals either received the PPAR α-antagonist GW6471 or the PPAR γ-antagonist GW9662 alone or combined with remote IPC. Infarct size was determined gravimetrically. Tissue levels of 15d-prostaglandin J2 (15d-PGJ2), as well as the PPAR DNA binding were measured using specific assays. Reverse transcriptase polymerase chain reaction was used to analyze changes in endothelial nitric oxide synthase or inducible nitric oxide synthase (iNOS) mRNA expression in relative quantity (RQ). Data are mean ± SD. As a result, remote IPC significantly reduced the myocardial infarct size (42.2 ± 4.9%* versus 61 ± 1.9%), accompanied by an increased PPAR DNA-binding (189.6 ± 19.8RLU* versus 44.4 ± 9RLU), increased iNOS expression (3.5 ± 1RQ* versus 1RQ), as well as 15d-PGJ2 levels (179.7 ± 7.9 pg/mL* versus 127.9 ± 7.6 pg/mL). The protective response elicited by remote IPC, as well as the accompanying molecular changes were abolished by inhibiting PPAR α (56.8 ± 4.7%; 61.1 ± 14.2RLU; and 1.91 ± 0.96RQ, respectively) or PPAR γ (57.4 ± 3.3%; 52.7 ± 16.9RLU; and 1.54 ± 0.25RQ, respectively). (*Significantly different from control P < 0.05). In conclusion, the obtained results indicate that both PPAR α and PPAR γ play an essential role in remote IPC against myocardial infarction, impinging on the transcriptional control of iNOS expression.

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%, P0.05), accompanied by significantly increased PPAR DNA binding (289.9 ± 33 versus 102.9 ± 18 relative light units, P0.05), as well as elevated tissue levels of 15d-PGJ(2) (224.4 ± 10.2 versus 116.9 ± 14.2 pg ml(-1), P0.05) and NO(x) (14.9 ± 0.7 versus 5.4 ± 0.7 μm, P0.05). 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 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.

Anesthetic preconditioning is mediated by beta-adrenergic signaling. This study was designed to elucidate the role of beta-adrenergic signaling in desflurane-induced postconditioning.Pentobarbital-anesthetized New Zealand White rabbits were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive vehicle (control), 1.0 minimum alveolar concentration of desflurane, esmolol (30 mg x kg(-1) x h(-1)) for the initial 30 min of reperfusion or throughout reperfusion, the beta2-adrenergic receptor blocker ICI 118,551 (0.2 mg/kg), the protein kinase A inhibitor H-89 (250 microg/kg), or the calcium/calmodulin-dependent protein kinase II inhibitor KN-93 (300 microg/kg) in the presence or absence of desflurane. Protein expression of protein kinase B, calcium/calmodulin-dependent protein kinase II, and phospholamban was measured by Western immunoblotting. Myocardial infarct size was assessed by triphenyltetrazolium staining.Infarct size was 57 +/- 5% in control. Desflurane postconditioning reduced infarct size to 36 +/- 5%. Esmolol given during the initial 30 min of reperfusion had no effect on infarct size (54 +/- 4%) but blocked desflurane-induced postconditioning (58 +/- 5%), whereas esmolol administered throughout reperfusion reduced infarct size in the absence or presence of desflurane to 42 +/- 6% and 41 +/- 7%, respectively. ICI 118,551 and KN-93 did not affect infarct size (62 +/- 4% and 62 +/- 6%, respectively) but abolished desflurane-induced postconditioning (57 +/- 5% and 64 +/- 3%, respectively). H-89 decreased infarct size in the absence (36 +/- 5%) or presence (33 +/- 5%) of desflurane.Desflurane-induced postconditioning is mediated by beta-adrenergic signaling. However, beta-adrenergic signaling displays a differential role in cardioprotection during reperfusion.

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.