Binnaz Ay

Effects of volatile anesthetics on store-operated Ca2+ influx in airway smooth muscle

Background:In airway smooth muscle (ASM), volatile anesthetics deplete sarcoplasmic reticulum (SR) Ca2+ stores by increasing Ca2+ “leak.” Accordingly, SR replenishment becomes dependent on Ca2+ influx. Depletion of SR Ca2+ stores triggers Ca2+ influx via specific plasma membrane channels, store-operated Ca2+ channels (SOCC). We hypothesized that anesthetics inhibit SOCC triggered by increased SR Ca2+ “leak,” preventing SR replenishment and enhancing ASM relaxation. Methods:In porcine ASM cells, SR Ca2+ was depleted by cyclopiazonic acid or caffeine in 0 extracellular Ca2+, nifedipine and KCl (preventing Ca2+ influx through L-type and SOCC channels). Extracellular Ca2+ was rapidly introduced to selectively activate SOCC. After SOCC activation, SR was replenished and the protocol repeated in the presence of 1 or 2 minimum alveolar concentration halothane, isoflurane, or sevoflurane. In other cells, characteristics of SOCC and interactions between acetylcholine (Ach) and volatile anesthetics were examined. Results:Cyclopiazonic acid produced slow SR leak, whereas the caffeine response was transient in ASM cells. Reintroduction of extracellular Ca2+ rapidly increased [Ca2+]i. This influx was insensitive to nifedipine, SKF-96365, and KBR-7943, inhibited by Ni2+ and blockade of inositol 1,4,5-triphosphate-induced SR Ca2+ release, and enhanced by ACh. Preexposure to 1 or 2 minimum alveolar concentration halothane completely inhibited Ca2+ influx when extracellular Ca2+ was reintroduced, whereas isoflurane and sevoflurane produced less inhibition. Only halothane and isoflurane inhibited ACh-induced augmentation of Ca2+ influx. Conclusion:Volatile anesthetics inhibit a Ni2+/La3+-sensitive store-operated Ca2+ influx mechanism in porcine ASM cells, which likely helps maintain anesthetic-induced bronchodilation.

Store-operated Ca2+ influx in airway smooth muscle: Interactions between volatile anesthetic and cyclic nucleotide effects.

Background:Volatile anesthetics produce bronchodilation in part by depleting sarcoplasmic reticulum Ca2+ stores in airway smooth muscle (ASM). Other bronchodilatory drugs are known to act via cyclic nucleotides (cyclic adenosine 3′,5′-cyclic monophosphate, cyclic guanosine 3′,5′-cyclic monophosphate). Intracellular Ca2+ regulation in ASM involves plasma membrane Ca2+ influx, including that triggered by sarcoplasmic reticulum Ca2+ depletion (store-operated Ca2+ entry [SOCE]). The authors hypothesized that anesthetics and bronchodilatory agents interact in inhibiting SOCE, thus enhancing ASM relaxation. Methods:In enzymatically dissociated porcine ASM cells imaged using fluorescence microscopy, sarcoplasmic reticulum Ca2+ was depleted by 1 &mgr;m cyclopiazonic acid in 0 extracellular Ca2+, nifedipine, and potassium chloride (preventing Ca2+ influx through L-type channels and SOCE). Extracellular Ca2+ was rapidly reintroduced to selectively activate SOCE in the presence or absence of 1 minimum alveolar concentration (MAC) halothane, isoflurane, or sevoflurane. Anesthetic interference with SOCE regulation by cyclic nucleotides was examined by activating SOCE in the presence of (1) 1 &mgr;m acetylcholine, (2) 100 &mgr;m dibutryl cyclic adenosine 3′,5′-cyclic monophosphate, or (3) 100 &mgr;m 8-bromo-cyclic guanosine 3′,5′-cyclic monophosphate. Results:SOCE was enhanced by acetylcholine, whereas volatile anesthetics and both cyclic nucleotides partially inhibited Ca2+ influx. Preexposure to 1 or 2 MAC anesthetic (halothane > isoflurane > sevoflurane) inhibited SOCE. Only halothane and isoflurane inhibited acetylcholine-induced augmentation of Ca2+ influx, and significantly potentiated cyclic nucleotide inhibition such that no influx was observed in the presence of anesthetics and cyclic nucleotides. Conclusions:These data indicate that volatile anesthetics prevent sarcoplasmic reticulum refilling by inhibiting SOCE and enhancing cyclic nucleotide blunting of Ca2+ influx in ASM. Such interactions likely result in substantial airway relaxation in the presence of both anesthetics and bronchodilatory agents such as β agonists or nitric oxide.

Spinal abscess after epidural anesthesia: need for more vigilance and better patient advice.

To JNA Readership: Development of a spinal epidural abscess after epidural catheterization is very rare, but it is the most serious late complication of this procedure. Anesthesiologists and surgeons should be aware of all the potential complications of this procedure and should warn patients about related signs and symptoms. In this letter we describe a patient in whom an epidural abscess was diagnosed 1 month after epidural anesthesia for total knee arthroplasty. A 77-year-old woman presented to our emergency clinic with severe lowback pain, urinary incontinence, and complete loss of sensation and complete loss of motor function of the left lower extremity. One month earlier she had undergone total left knee arthroplasty with epidural anesthesia. Apart from the knee problem, she had been in good health prior to presentation. Three weeks after the operation, she started to experience pain in her knee and lower back, which had gradually worsened in the week prior to presentation. The patient first noticed pins-and-needles sensation in the operated leg by postoperative day 30; this had progressed to complete loss of sensation and complete loss of motor function. Laboratory studies at admission revealed peripheral white blood cell count 13,200/mm, erythrocyte sedimentation rate 75 mm/h, and serum C-reactive protein 79 mg/dL. An ELISA test for human immunodeficiency virus was negative. Magnetic resonance imaging of the lumbar spine demonstrated a multilobular cystic mass that measured 18 × 16 × 78 mm and extended from T12 to L5. The lesion was heterogeneously hypointense on T1-weighted images (Figs. 1 and 2 left) and heterogeneously hyperintense on T2-weighted images (Figs. 1 and 2 right), and showed mild enhancement after intravenous injection of gadolinium. The differential diagnosis was epidural hematoma or abscess, and emergency surgery was carried out immediately. A midline posterior skin incision was made from T12 to S1, and laminectomies were performed at L1, L2, and L4. This exposed a massive epidural abscess that filled the entire surgical field. A sample of abscess material was collected for microbiological examination, and then antibiotic therapy was started with cefazolin sodium 1 g given intravenously. This treatment was continued three times daily postoperatively. The abscess was carefully drained, and the surgical field was irrigated with physiologic saline and hydrogen peroxide. A drain was placed in the epidural space and left in position for 48 hours postoperatively. Gram staining of a specimen of the drainage material revealed grampositive cocci. Methicillin-sensitive Staphylococcus aureus was subsequently isolated from cultures of the abscess material. The loss of motor function and sensation in the patient’s left leg resolved in the first week after surgery. After 3 weeks of parenteral antibiotics, she was discharged on a 4-week course of oral trimethoprim-sulfamethoxazole 1 g twice daily. A recheck in the eighth week after surgery revealed complete recovery, and there was no abscess recurrence during follow-up. Development of spinal epidural abscess after epidural anesthesia is one of the most serious complications of epidural anesthesia. The reported incidence rates range from 1 in 506,000 obstetric cases to 3% in cases requiring chronic pain management. Staphylococcal species are the most common causative organisms in spinal epidural abscess. Diabetes mellitus, chronic renal failure, immune incompetence, and alcoholism are frequent predisposing factors in patients with epidural abscess. Our patient had none of these risk factors, but epidural anesthesia itself is a risk factor for spinal epidural abscess. Strict attention to sterile technique is crucial when performing epidural catheterization. In research on 40 cases of spinal epidural abscess, Hlawin et al found that skin and soft-tissue injuries were the main routes of bacterial entry. The break in the skin is a potential site of entry for infectious microorganisms, and several methods for cleansing the FIGURE 1. MRI showing T1-weighted (left) and T2-weighted (right) sagittal images.

Co-existence of Pott's disease and alkaptonuria in a 21-month-old child.

reported in a case with PDA 30 h after the procedure (4). The migrated devices are usually removed surgically, whereas in the presented case the device was removed by endovascular techniques. Two patients had late complications: peripheral embolization in the left leg 1 year after implantation of an Amplatzer device and sudden death 1.5 year later (2). In such procedures, regardless of the occluder type, the migration of device can happen in 1.1% of the cases and surgical removal is required in 0.2% of all the cases (3). Early and easy migration of the device can be caused by the technical reasons like inappropriate choice of the device (insufficient length of the rim). Device-defect ratio also had a significant effect on delivery success and composite success. Defect stretch diameter had the largest influence on outcome, and implantation was possible in only 67% if the stretched diameter of the defect was >20 mm (5). The other possible causes of migration of the device are either because of choice of the occluder or less experience in application of the device. The migration of the device in percutaneous transcatheter occlusion procedures may cause life-threatening complications and we suggest that all patients should go to intensive care unit postoperatively. The anesthesiologists should be careful to the developing techniques and complications of such procedures. Yusuf Unal M D* Serdar Kula M D† Gokcen Emmez M D* Rana Olgunturk M D† Sahin Yardim M D* *Department of Anesthesiology and Reanimation and †Department of Pediatric Cardiology, Gazi University School of Medicine, Ankara, Turkey (email: yunal71@yahoo.com, yunal@gazi.edu.tr) References