Myocardial sympathetic denervation prevents chamber-specific alteration of beta-adrenergic transmembrane signaling in rabbits with heart failure

Objectives.The purpose of this study was to assess the effect of myocardial sympathetic denervation on the chamber-specific alteration of beta-adrenergic signaling in left ventricular failure in rabbits.Background.Local abnormalities in sympathetic nerve terminals, including the neuronal reuptake of norepinephrine, are thought to be responsible for the chamber-specific regulation of beta-adrenergic signaling in heart failure.Methods.Sixteen rabbits were given 6-hydroxydopamine, 25 mg/kg body weight intravenously on days 1 and 2 and 50 mg/kg intravenously on days 7 and 8. Another 16 rabbits received vehicle. Aortic regurgitation was induced in eight of the 6-hydroxydopamine—treated and eight of the vehicle-treated rabbits on day 14. Another eight of the 6-hydroxydopamine—treated and eight of the vehicletreated rabbits underwent a sham operation. The hearts were excised for biochemical analysis on day 21.Results.Hemodynamic characteristics on day 21 showed left ventricular failure in both the aortic regurgitation groups. The plasma norepinephrine concentration on day 21 was higher in both the aortic regurgitation groups than in the sham groups. The beta-adrenoceptor densities and isoproterenol plus 5′guanylylimidodiphosphate-, 5′-guanylylimidodiphosphate- and sodium fluoride-stimulated adenylyl cyclase activities were decreased only in the failing left ventricle of the vehicle-pretreated aortic regurgitation group, but in both ventricles of the 6-hydroxydopamine-pretreated aortic regurgitation group. The basal and forskolin-stimulated adenylyl cyclase activities were similar in both the aortic regurgitation groups and in the sham groups.Conclusions.Sympathetic denervation prevented chamberspecific alterations in beta-adrenergic signaling in acute left ventricular failure. Local loss of sympathetic nerve endings, and especially the defective neuronal norepinephrine reuptake, are likely to be responsible for the chamber-specific alteration of the beta-adrenoceptor-G protein-adenylyl cyclase system in heart failure in rabbits

国際規格ISO 10139-1による市販ティッシュコンディショナーの比較検討

The aim of this study was to analyze the composition of eight commercial tissue conditioners, assess each material using the International Standard (ISO) 10139-1 and relate differences in properties to composition. A visible light spectrophotometer (IR-460: Shimadzu, Kyoto, Japan) was used to analyze the principal components of both liquids and polymer powders. A High Pressure Liquid Chromatograph (HPLC: Shimadzu, Kyoto, Japan) was used to measure the principal ingredients. A gas chromatograph (GC-15A: Shimadzu, Kyoto, Japan) was used to measure the alcohol concentration. Consistency and penetration tests were carried out as detailed in the ISO 10139-1. The penetration test measurements were also made at 2, 3 and 4 weeks. All materials satisfied the standard in the consistency test and in the penetration test after one week. However, three materials failed to satisfy the standard in the penetration test after two hours. In all materials the powder was found to be poly (ethyl methacrylate), while plasticizers and ethanol content varied. Two materials contained other components thought to be antibiotic or antibacterial agents. There appeared to be a correlation between the ethanol content and the consistency results

Direct and Specific Effect of Sevoflurane Anesthesia on <em>rat Per2</em> Expression in the Suprachiasmatic Nucleus

<div><p>Background</p><p>Our previous studies revealed that application of the inhalation anesthetic, sevoflurane, reversibly repressed the expression of <i>Per2</i> in the mouse suprachiasmatic nucleus (SCN). We aimed to examine whether sevoflurane directly affects the SCN.</p> <p>Methods</p><p>We performed <i>in vivo</i> and <i>in vitro</i> experiments to investigate rat <i>Per2</i> expression under sevoflurane-treatment. The <i>in vivo</i> effects of sevoflurane on <i>rPer2</i> expression were examined by quantitative <i>in situ</i> hybridization with a radioactively-labeled cRNA probe. Additionally, we examined the effect of sevoflurane anesthesia on rest/activity rhythms in the rat. In the <i>in vitro</i> experiments, we applied sevoflurane to SCN explant cultures from <i>Per2-dLuc</i> transgenic rats, and monitored luciferase bioluminescence, representing <i>Per2</i> promoter activity. Bioluminescence from two peripheral organs, the kidney cortex and the anterior pituitary gland, were also analyzed.</p> <p>Results</p><p>Application of sevoflurane in rats significantly suppressed <i>Per2</i> expression in the SCN compared with untreated animals. We observed no sevoflurane-induced phase-shift in the rest/activity rhythms. In the <i>in vitro</i> experiments, the intermittent application of sevoflurane repressed the increase of <i>Per2-dLuc</i> luminescence and led to a phase delay in the <i>Per2-dLuc</i> luminescence rhythm. Sevoflurane treatment did not suppress bioluminescence in the kidney cortex or the anterior pituitary gland.</p> <p>Conclusion</p><p>The suppression of <i>Per2-dLuc</i> luminescence by sevoflurane in <i>in vitro</i> SCN cultures isolated from peripheral inputs and other nuclei suggest a direct action of sevoflurane on the SCN itself. That sevoflurane has no such effect on peripheral organs suggests that this action might be mediated through a neuron-specific cellular mechanism or a regulation of the signal transduction between neurons.</p> </div

Measurements of body temperature and O₂ saturation (SpO₂).

<p>(A) The body temperature of rats was measured rectally before and during anesthesia. (B) The O₂ saturation of rats was measured in the thigh during anesthesia. Values are expressed as means ± SD (n = 4).</p

Responses of cultured tissue under anesthetic treatment.

<p>(A) The main panel shows the bioluminescence from an SCN slice during intermittent application of sevoflurane (red) or of airflow alone (black). The inset panel at the lower left demonstrates the definition of inter-peak length, while the inset lower right shows a comparison of inter-peak lengths under air and sevoflurane application. Data are mean ± SD (n = 5 for each group). ^*denotes a statistically significant difference (Student’s t-test, <i>p</i><0.05). (B) Bioluminescence from slices of kidney cortex (left) and the pituitary gland (right) with intermittent application of sevoflurane (red) or of airflow (black).</p

Effects of sevoflurane-anesthesia on <i>Per2</i> expression in the SCN <i>in vivo</i>.

<p>(A) The light/dark conditions, time of anesthesia and time of sampling in the experiment are illustrated. White and black bars indicate light and dark periods, respectively. Gray rectangles indicate the period of anesthetic treatment during the daytime (08∶00–16∶00). (B) Typical images of <i>in situ</i> hybridization. Labels indicate the sampling time and anesthetic treatment. (C) Intensity of <i>Per2</i> mRNA expression on the day of anesthetic treatment. Expression of <i>Per2</i> in non-treated (open squares) and treated (closed squares) rats in the DD condition. Data are mean ± SD. ^*denotes a significant difference (two-way ANOVA, <i>p</i><0.05) between the groups at the indicated time point. Same alphabetic annotation denotes non-significant difference between time points within the same group.</p