Differential Effects of Anesthetics on Mitochondrial KATP Channel Activity and Cardiomyocyte Protection

Background: Mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels play a pivotal role in mediating cardiac preconditioning. The effects of intravenous anesthetics on this protective channel have not been investigated so far, but would be of importance with respect to experimental as well as clinical medicine.

Methods: Live cell microscopy was used to visualize and measure autofluorescence of flavoproteins, a direct reporter of mitoKATP channel activity, in response to the direct and highly selective mitoKATP channel opener diazoxide, or to diazoxide following exposure to various anesthetics commonly used in experimental and clinical medicine. A cellular model of ischemia with subsequent hypoosmolar trypan blue staining served to substantiate the effects of the anesthetics on mitoKATP channels with respect to myocyte viability.

Results: Diazoxide-induced mitoKATP channel opening was significantly inhibited by the anesthetics R-ketamine, and the barbiturates thiopental and pentobarbital. Conversely, urethane, 2,2,2-trichloroethanol (main metabolite of [alpha]-chloralose and chloral hydrate), and the opioid fentanyl potentiated the channel-opening effect of diazoxide, which was abrogated by coadministration of chelerythrine, a specific protein kinase C inhibitor. S-ketamine, propofol, xylazine, midazolam, and etomidate did not affect mitoKATP channel activity. The significance of these modulatory effects of the anesthetics on mitoKATP channel activity was substantiated in a cellular model of simulated ischemia, where diazoxide-induced cell protection was mitigated by R-ketamine and the barbiturates, while urethane, 2,2,2-trichloroethanol, and fentanyl potentiated myocyte protection.     

Adrenergic Receptor Genotype but Not Perioperative Bisoprolol Therapy May Determine Cardiovascular Outcome in At-risk Patients Undergoing Surgery with Spinal Block: The Swiss Beta Blocker in Spinal Anesthesia (BBSA) Study: A Double-blinded, Placebo-controlled, Multicenter Trial with 1-Year Follow-up

Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block.

Methods: The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined.

Results: A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the [beta]1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04).     

Creatine kinase isoenzyme (CK-BB) in combination to prostatic acid phosphatase measured by RIA in the diagnosis of prostatic cancer

Summary Creatine kinase isoenzyme (CK-BB) measured by mass was used to determine its value in the early diagnosis of prostatic cancer. Sera of patients with prostatic carcinoma of various stages (treated and untreated) were compared to normal male sera and sera of patients with benign hyperplasia of the prostate (BPH) with respect to CK-BB. The sera were simultaneously tested for PAP content. The sensitivity of the CK-BB-RIA was 1.63+/-0.08 g/l and reproducibility in the higher and lower concentration range 7.6% and 10.5%, respectively. CK-BB alone or in combination with PAP is no marker for early detection of prostatic cancer. In individual cases changes occurred similar to those found with a malignant growth of the prostate.     

Purification and characterization of a juvenile hormone binding protein from the hemolymph of the fourth instar tobacco hornworm, Manduca sexta

A protein which binds the insect juvenile hormone has been isolated from the hemolymph of the fourth instar tobacco hornworm, Manduca sexta (Lepidoptera). Bioassay and chemical characterization of the bound ligand from the purified binding protein indicates that this molecule is the primary macromolecule responsible for juvenile hormone transport in the hemolymph of this insect. The juvenile hormone binding protein has been purified using gel filtration, ion exchange chromatography and preparative polyacrylamide gel electrophoresis. The protein is a single polypeptide chain of about 28,000 daltons with a sedimentation coefficient of 2.2S and an isoelectric point of 5.0. Binding analysis using a hydroxyapatite batch assay indicates that the juvenile hormone binding protein has one binding site with a Ka of 1.2 times 10(7) M-1 at 4 degrees C.     

Implant-supported mandibular splinting affects temporomandibular joint biomechanics

Objectives: Mandibular functional movements lead to complex deformations of bony structures. The aim of this study was to test whether mandibular splinting influences condylar kinematics and temporomandibular joint (TMJ) loading patterns. Materials and methods: Six subjects were analyzed by means of dynamic stereometry during jaw opening–closing with mandibles unconstrained as well as splinted transversally by a cast metal bar fixed bilaterally to two implant pairs in the (pre)molar region. Statistical analysis was performed by means of ANOVAs for repeated measurements (significance level α=0.05). Results: Transversal splinting reduced mandibular deformation during jaw opening–closing as measured between two implants in the (pre)molar region on each side of the mandible significantly by 54%. Furthermore, splinting significantly reduced the distance between lateral condylar poles (average displacement vector magnitude of each pole: 0.84±0.36 mm; average mediolateral displacement component: 45±28% of the magnitude) and led to a medial displacement of their trajectories as well as a mediolateral displacement of stress‐field paths. Conclusions: During jaw opening–closing, splinting of the mandible leads to a significant reduction of mandibular deformation and intercondylar distance and to altered stress‐field paths, resulting in changed loading patterns of the TMJ structures. To cite this article:
Zaugg B, Hämmerle CHF, Palla S, Gallo LM. Implant‐supported mandibular splinting affects temporomandibular joint biomechanics.
Clin. Oral Impl. Res. 23 , 2012; 897–901
doi: 10.1111/j.1600‐0501.2011.02241.x     

Significant reduction in systolic blood pressure following renal artery stenting in patients with uncontrolled hypertension: Results from the HERCULES trial

Background : Atherosclerotic renal artery stenosis (ARAS) causes hypertension (HTN) and threatens renal function (RF). The HERCULES Trial is a prospective, multicenter trial of renal stenting in patients with uncontrolled HTN and ARAS evaluating the safety and effectiveness of the RX Herculink Elite Renal Stent System (Abbott Vascular, Santa Clara, CA). Results : Mean systolic blood pressure (SBP) at baseline was 162 mm Hg. Nearly 70% of patients were receiving three or more antihypertensive medications (mean 3.4 medications per patient). Baseline serum creatinine was 1.2 ± 0.4 and 61.5% of subjects had estimated glomerular filtration <60. The restenosis rate was 10.5% at 9 months. The study device, procedure, and clinical success rates were 96.0, 99.2, and 98.0%, respectively. Freedom from major adverse events was 94.8%. At 9 months, the mean SBP significantly decreased (mean 145, paired t test P < 0.0001) after stenting with no change in medications. There was no correlation between SBP reduction and baseline BNP or BNP reduction. 相似文献   

The periosteal-cutaneous chimeric medial femoral condyle free flap for subtotal ear reconstruction: A case report

When costal graft is contraindicated or refused by the patient, autologous total/subtotal auricular reconstruction represent a real challenge as limited surgical options has been described. Aim of present report is to offer a novel possible autologous reconstruction of the ear frame using a chimeric free medial femoral condyle (MFC) flap. We present a case of a 29 years old patient who had total loss of the upper 2/3 of the right ear after bombing in Somalia and secondary infected condritis (considered a relative contraindication for costal cartilage graft). The MFC flap was harvested with a chimeric skin paddle (7 × 5 cm), a thin sheet of femoral cortex (6.5 × 8 cm) was used as basal ear frame, while part of the contralateral concha was trimmed as support for the helix, with the periosteal component of the flap wrapping around the whole framework. The chimeric skin paddle assured the retroauricular skin coverage, while the anterior part of the construct was covered by a thinned dermal flap. Postoperative course was uneventful. A defatting procedure of the posterior skin paddle was performed at 2 months post-op. At 6 months post-op, the patient was satisfied with the result, could wear glasses and was socially integrated. This new application of the free chimeric MFC flap, despite being not the primary choice for ear reconstruction, guaranteed satisfactory results in terms of ear shape and infection prevention and may be considered when ordinary cartilage rib reconstruction is refused, contraindicated, or failed.     

Modulation of beta-adrenergic receptor subtype activities in perioperative medicine: mechanisms and sites of action

This review focuses on the mechanisms and sites of action underlyingß-adrenergic antagonism in perioperative medicine.A large body of knowledge has recently emerged from basic andclinical research concerning the mechanisms of the life-savingeffects of ß-adrenergic antagonists (ß-AAs)in high-risk cardiac patients. This article re-emphasizes themechanisms underlying ß-adrenergic antagonism andalso illuminates novel rationales behind the use of perioperativeß-AAs from a biological point of view. Particularly,it delineates new concepts of ß-adrenergic signaltransduction emerging from transgenic animal models. The roleof the different characteristics of various ß-AAsis discussed, and evidence will be presented for the selectionof one specific agent over another on the basis of individualdrug profiles in defined clinical situations. The salutary effectsof ß-AAs on the cardiovascular system will be describedat the cellular and molecular levels. ß-AAs exhibitmany effects beyond a reduction in heart rate, which are lessknown by perioperative physicians but equally desirable in theperioperative care of high-risk cardiac patients. These includeeffects on core components of an anaesthetic regimen, such asanalgesia, hypnosis, and memory function. Despite overwhelmingevidence of benefit, ß-AAs are currently under-utilizedin the perioperative period because of concerns of potentialadverse effects and toxicity. The effects of acute administrationof ß-AAs on cardiac function in the compromised patientand strategies to counteract potential adverse effects willbe discussed in detail. This may help to overcome barriers tothe initiation of perioperative treatment with ß-AAsin a larger number of high-risk cardiac patients undergoingsurgery. Br J Anaesth 2002; 88: 101–23