Kenji Shigemi

Single-beat Estimation of Ventricular End-systolic Elastance–Effective Arterial Elastance as an Index of Ventricular Mechanoenergetic Performance

Background The ratio of ventricular end-systolic elastance (Ees) to effective arterial elastance (Ea) is known to reflect not only ventricular mechanical performance but also energetic performance. Despite these useful features, technical difficulties associated with estimating Ees make the clinical application of Ees/Ea impractical. We developed a framework to estimate Ees/Ea without measuring ventricular volume or altering the loading condition. Methods To achieve this goal, we approximated the ventricular time-varying elastance curve with two straight lines, one for the isovolumic phase and the other for the ejection phase, and characterized the curve with the slope ratio, k, of these two straight lines. Using the concept of the pressure–volume relationship, Ees/Ea is algebraically expressed as Ees/Ea = Pad/Pes (1 + k · ET/PEP) − 1, where Pes is end-systolic pressure, Pad is aortic diastolic pressure, ET is ejection time, and PEP is pre-ejection period. In 11 anesthetized dogs, we recorded arterial and ventricular pressures and ventricular volume and estimated Ees and Ea under various contractile states and loading conditions. Results An empirical relation between k and Ees/Ea was found as k = 0.53 (Ees/Ea)0.51. Simultaneous solution of these two equations yielded Ees/Ea as a function of Pad/Pes and ET/PEP. The estimated Ees/Ea values correlated well with the measured Ees/Ea values ([Measured Ees/Ea] = 0.96 [Estimated Ees/Ea] + 0.098, r = 0.925, SEE = 0.051). Conclusions The proposed framework is capable of estimating Ees/Ea from ventricular and aortic pressure.

Neonatal electroencephalography shows low sensitivity to anesthesia

This study examined EEG under clinical anesthesia in neonates and infants, to clarify how growth affects EEG during anesthesia. Subjects comprised 62 neonates and infants. Patients were divided into four groups according to age: Group 1 (neonates), <1 month; Group 2, 1-2 months; Group 3, 3-5 months; and Group 4, 6 months to 2 years. Anesthesia was maintained with sevoflurane and fentanyl and/or caudal block. At four points of sevoflurane concentration (0.5%, 1%, 1.5%, and 2%), 90% spectral edge frequency (SEF90), burst suppression ratio (BSR), relative beta ratio (RBR) and approximate entropy (ApEn) were analyzed. In Group 4, SEF90, BSR, RBR and ApEn changes were dependent on the concentration of anesthesia, along with changes in sevoflurane concentration from 0.5% to 2% (from 14.3 (2.7) [mean (SD)] Hz to 8.2 (3.8) Hz, from 0.0 to 0.32 (0.36), from -1.58 (0.14) to -1.10 (0.15), and from 0.56 (0.25) to 0.24 (0.25) respectively; p<0.05 each). Conversely, these processed EEG parameters in Group 1 showed little anesthesia-dependent change under sevoflurane concentrations between 0.5% and 2% (SEF90: 7.3 (1.2) Hz vs. 7.7 (2.1) Hz; BSR: 0.51 (0.20) vs. 0.62 (0.29); RBR: -1.00 (0.17) vs. -1.03 (0.27); ApEn: 0.32 (0.18) vs. 0.25 (0.14), respectively). The unique EEG features of neonates during anesthesia rapidly change to the usual anesthesia-dependent patterns seen in older children, with a boundary of 3-5 months old. In infants younger than 6 months old, neural network regulation reflected in EEG by anesthesia is weak.

Rectified Proton Grotthuss Conduction Across a Long Water-Wire in the Test Nanotube of the Polytheonamide B Channel

A hydrogen-bonded water-chain in a nanotube is highly proton conductive, and examining the proton flux under electric fields is crucial to understanding the one-dimensional Grotthuss conduction. Here, we exploited a nanotube-forming natural product, the peptide polytheonamide B (pTB), to examine proton conduction mechanisms at a single-molecule level. The pTB nanotube has a length of ∼40 Å that spans the membrane and a uniform inner diameter of 4 Å that holds a single-file water-chain. Single-channel proton currents were measured using planar lipid bilayers in various proton concentrations and membrane potentials (±400 mV). We found, surprisingly, that the current-voltage curves were asymmetric with symmetric proton concentrations in both solutions across the membrane (rectification). The proton flux from the C-terminal to the N-terminal end was 1.6 times higher than that from the opposite. At lower proton concentrations, the degree of rectification was attenuated, but with the addition of a pH-buffer (dichloroacetate) that supplies protons near the entrance, the rectification emerged. These results indicate that the permeation processes inside the pore generate the rectification, which is masked at low concentrations by the diffusion-limited access of protons to the pore entrance. The permeation processes were characterized by a discrete-state Markov model, in which hops of a proton followed by water-chain turnovers were implemented. The optimized model revealed that the water-chain turnover exhibited unusual voltage dependence, and the distinct voltage-dependencies of the forward and backward transition rates yielded the rectification. The pTB nanotube serves as a rectified proton conductor, and the design principles can be exploited for proton-conducting materials.

Effect of anaesthesia maintained with sevoflurane and propofol on surgical site infection after elective open gastrointestinal surgery.

Perioperative increase in oxidative activity in surgical patients reportedly prevents postoperative surgical site infection (SSI). Several clinical studies have shown that oxidative activity under sevoflurane anaesthesia was higher than that under propofol anaesthesia. Therefore, we hypothesised that sevoflurane anaesthesia would discourage SSI compared with propofol anaesthesia. To examine the effect of anaesthesia maintained with sevoflurane and propofol on SSI, a total of 265 consecutive adult patients, with American Society of Anesthesiologists physical status 1-3, who underwent elective open gastrointestinal surgery under general anaesthesia, were surveyed for SSI between January 2007 and December 2008. Sevoflurane or propofol was selected to maintain anaesthesia in 95 and 170 patients, respectively. A propensity score was used for pairwise matching of these patients to avoid selection biases between the two methods of anaesthesia. Propensity matching yielded 84 pairs of patients. We compared standardised infection ratios (SIRs), i.e. the quotient of the number of SSI cases observed and the number of SSI cases expected, calculated using data from the National Nosocomial Infection Surveillance, between sevoflurane and propofol anaesthesia. After propensity matching, SIR after sevoflurane anaesthesia was 1.89 [95% confidence interval (CI): 1.46-2.32], which was significantly lower than after propofol anaesthesia (4.78; 95% CI: 4.30-5.27) (P=0.02). This study suggests that sevoflurane tends to suppress SSI after elective open gastrointestinal surgery compared with propofol.

Increasing Membrane Interactions of Local Anaesthetics as Hypothetic Mechanism for Their Cardiotoxicity Enhanced by Myocardial Ischaemia

While myocardial ischaemia enhances the cardiotoxicity of local anaesthetics, the pharmacological background remains unclear. Cardiolipin (CL) localized in mitochondrial membranes is possibly the site of cardiotoxic action of local anaesthetics and peroxynitrite is produced by cardiac ischaemia and reperfusion. We verified the hypothetic mechanism that local anaesthetics may interact with CL‐containing biomembranes to change the membrane biophysical property and their membrane interactions may be increased by peroxynitrite. Biomimetic membranes were prepared with different phospholipids and cholesterol of varying compositions. The membrane preparations were reacted with peroxynitrite of pathologically relevant concentrations and local anaesthetics (bupivacaine and lidocaine) of a cardiotoxic concentration separately or in combination. Changes in membrane fluidity were determined by measuring fluorescence polarization. Peroxynitrite decreased the fluidity of biomimetic membranes at 0.1–10 μM with the relative potency being CL>1‐stearoyl‐2‐arachidonoylphosphatidylcholine>1,2‐dipalmitoylphosphatidylcholine‐constituting membranes, indicating the lipid peroxidation‐induced membrane rigidification determined by the unsaturation degree of membrane lipids. When treated with 0.1–10 μM peroxynitrite, biomimetic membranes were more rigid with elevating the CL content from 0% to 30 mol%, suggesting that CL is a primary target of peroxynitrite. Bupivacaine and lidocaine fluidized at 200 μM biomimetic membranes containing 10 mol% CL and their effects were increased by pre‐treating the membranes with 0.1 and 1 μM peroxynitrite. Cardiotoxic bupivacaine and lidocaine increasingly interact with CL‐containing mitochondria model membranes which are relatively rigidified by peroxynitrite. Such an increasing membrane interaction may be, at least in part, responsible for the local anaesthetic cardiotoxicity enhanced by myocardial ischaemia.

A comparative study of measurement of arterial blood pressure using HEM-802F and arterial cannulation.

Finger arterial blood pressures determined by a newly developed sphygmomanometer, HEM-802F, were compared with arterial pressure obtained from direct measurement of the radial artery. An excellent correlation was found between the two methods (systolic: r =0.93, diastolic: r =0.91), although there was a large variability among individual subjects. The range of differences between them are from +32 to −13 mmHg for systolic and +15 to −25 mmHg for diastolic blood pressure measurement. HEM-802F underestimated systolic pressure (−4.0 mmHg) and overes timated diastolic pressure (+6.7 mmHg), compared with intra-arterial readings.The HEM-802F was useful for the non-invasive arterial pressure monitoring during general anesthesia.

Reliability and validity of the Japanese translation of the DN4 Diagnostic Questionnaire in patients with neuropathic pain

BackgroundThe Douleur Neuropathique 4 questionnaire (DN4) is a simple and objective tool developed by the French Neuropathic Pain Group to screen for neuropathic pain.MethodsThis prospective observational study was undertaken in three hospitals to assess the validity of a Japanese translation of the DN4. We first translated the DN4 into Japanese using a forward–backward method. Pain specialists then examined patients independently and diagnosed them with neuropathic or non-neuropathic pain, according to the International Association for the Study of Pain definitions. The Japanese version of the DN4 questionnaire was then given to each patient.ResultsOf 187 patients that met our inclusion criteria, 100 and 87 were diagnosed with neuropathic and non-neuropathic pain, respectively. The test–retest intra-class correlation coefficient (95% confidence interval) was 0.827 (0.769–0.870). Among patients with identical diagnoses of neuropathic or non-neuropathic pain, receiver-operating characteristic curve analysis revealed an area under the curve of 0.89. A cut-off point of equal or greater than 4 resulted in a sensitivity of 71% and specificity of 92%.ConclusionThe Japanese version of the DN4 was found to be a helpful tool for discriminating between neuropathic and non-neuropathic pain.

A Case of Anaphylactic Shock Diagnosed on Second Implementation of Anesthetic Management

著者連絡先 松木悠佳 〒 910-1193 福井県吉田郡永平寺町松岡下合月 23-3 福井大学学術研究院医学系部門医学領域 器官制御医学講座麻酔・蘇生学 タニルで麻酔を導入し,ロクロニウム投与後に気管 挿管した.挿管後に血圧が36/26mmHgに低下し, エフェドリン,フェニレフリン,ノルアドレナリン の投与を行ったが反応は乏しかった.皮膚の発赤や 気道内圧上昇は見られなかった.心エコーで,左心 室壁運動や弁に異常はないが心腔容積の減少を認め たため循環血液量減少と判断した.急速輸液と塩酸 ドパミン持続投与で血圧は徐々に上昇した.術中ロ クロニウムの追加投与は必要としなかった. 2カ月後に,くも膜下出血後の水頭症に対し脳室腹腔シャント術(VPシャント術)を予定した.1回 目と同様に麻酔導入し気管挿管した.血圧が35/ 27mmHgに低下したため,エフェドリンを投与し たが血圧は上昇しなかった.全身の発赤に気づきア ナフィラキシーを疑い,アドレナリン,メチルプレ ドニゾロンを静脈内投与し,手術は中止した.同時 はじめに

Correction to: Physiological insights of recent clinical diagnostic and therapeutic technologies for cardiovascular diseases

The article Physiological insights of recent clinical diagnostic and therapeutic technologies for cardiovascular diseases, written by Kenji Shigemi, Soichiro Fuke, Dai Une, Keita Saku, Shuji Shimizu, Toru Kawada, Toshiaki Shishido, Kenji Sunagawa and Masaru Sugimachi, was originally published Online First without open access.

Physiological insights of recent clinical diagnostic and therapeutic technologies for cardiovascular diseases

Diagnostic and therapeutic methods for cardiovascular diseases continue to be developed in the 21st century. Clinicians should consider the physiological characteristics of the cardiovascular system to ensure successful diagnosis and treatment. In this review, we focus on the roles of cardiovascular physiology in recent diagnostic and therapeutic technologies for cardiovascular diseases. In the first section, we discuss how to evaluate and utilize left ventricular arterial coupling in the clinical settings. In the second section, we review unique characteristics of pulmonary circulation in the diagnosis and treatment of pulmonary hypertension. In the third section, we discuss physiological and anatomical factors associated with graft patency after coronary artery bypass grafting. In the last section, we discuss the usefulness of mechanical ventricular unloading after acute myocardial infarction. Clinical development of diagnostic methods and therapies for cardiovascular diseases should be based on physiological insights of the cardiovascular system.