南 浩一郎

The effects of isoflurane on Na-22(+) influx, Ca-45(2+) influx, catecholamine secretion and cyclic GMP production induced by three kinds of secretagogue (nicotinic agonists, veratridine and a high concentration of K+) have been investigated using cultured bovine adrenal medullary cells. (1) Isoflurane (1-6%) inhibited catecholamine secretion stimulated by carbachol, nicotine and dimethyl-4-phenylpiperazinium in a concentration-dependent manner. Isoflurane suppressed carbachol-evoked Na-22(+) influx and Ca-45(2+) influx at concentrations similar to those which suppressed catecholamine secretion. The inhibition of catecholamine secretion by isoflurane was not overcome by increasing the concentration of carbachol. (2) The inhibitory effects of isoflurane on veratridine-induced Na-22(+) influx, Ca-45(2+) influx and catecholamine secretion became evident when the concentration of isoflurane was raised to 4-6%, i.e. 2-3 fold higher than the concentrations (1-2%) employed clinically. (3) High K+-evoked Ca-45(2+) influx and catecholamine secretion were not affected by isoflurane (1-6%). (4) Isoflurane (1-6%) attenuated the production of cyclic GMP caused by muscarine, but not that caused by atrial natriuretic peptide or by sodium nitroprusside. These results suggest that isoflurane, at clinical anesthetic concentrations, inhibits nicotinic acetylcholine receptor-mediated cell responses as well as muscarinic receptor-mediated cyclic GMP production in adrenal medullary cells.

We investigated the effect of recombinant human interleukin-1 beta (IL-1 beta) on catecholamine secretion from cultured bovine adrenal medullary cells. Treatment of cultured cells with IL-1 beta (10 ng/ml) for 24 hr caused an increase in accumulation of catecholamines in the cultured medium. The accumulation of catecholamines stimulated by IL-1 beta was observed in time (4-48 hr)- and concentration (3-30 ng/ml)-dependent manners. The stimulatory effect of IL-1 beta (10 ng/ml) was completely inhibited by recombinant human IL-1 receptor antagonist (1 microgram/ml). IL-1 beta had little effect on [3H]norepinephrine uptake to cultured cells. These results suggest that IL-1 beta stimulates catecholamine secretion through activation of IL-1 receptors in adrenal medullary cells.

We examined the effects of C-type natriuretic peptide (CNP) on cyclic GMP production and catecholamine synthesis in cultured bovine adrenal medullary cells. 1) CNP increased intracellular cyclic GMP content in a concentration- dependent manner (10-1000 nM). 2) The cyclic GMP production induced by 1 μM CNP reached a 200-fold increase, and the effect of CNP was most potent among the natriuretic peptide family. 3) The CNP-induced cyclic GMP production was attenuated by endothelin (1 μM) and angiotensin II (0.1-1 μM). 4) When the cells were cultured with hypertonic NaCl medium, the CNP-induced cyclic GMP production was potentiated in a time (1-4 days)- and concentration (25-100 mM)-dependent manner. 5) CNP stimulated the synthesis of 14C-labeled catecholamines from [14C]tyrosine but not from [14C]dopa. The stimulatory effect of CNP on the 14C-labeled catecholamine synthesis was observed at the concentrations of 100 to 1000 nM. 6) 8-Bromo cyclic GMP, a membrane- permeable cyclic GMP analog, and sodium nitroprusside, an activator of soluble guanylate cyclase, also stimulated the synthesis of 14C-labeled catecholamines from [14C]tyrosine, whereas C-ANP, a specific ligand for the ANP-C (clearance) receptor that does not increase cyclic GMP content, failed to stimulate the synthesis of 14C-labeled catecholamines. 7) CNP (1 μM) as well as 8-bromo cyclic GMP and sodium nitroprusside increased the activity of tyrosine hydroxylase in the cells. These results suggest that in the adrenal medulla, CNP is a potent agonist for cyclic GMP production, which is modulated by endothelin, angiotensin II and the hypertonic NaCl condition. CNP may stimulate the catecholamine synthesis through the cyclic GMP- dependent activation of tyrosine hydroxylase in the adrenal medulla.

To characterize sites of action of C-type natriuretic peptide (CNP) in the glial cells, the effect of CNP on cGMP accumulation and the binding of [I-125]CNP in rat astrocyte RCR-1 cells were studied. CNP stimulated cGMP accumulation in the cells from 10(-9)) M in a dose-dependent manner, but ANP (atrial natriuretic peptide) had a negligible effect on cGMP accumulation in the cells. [I-125]CNP was bound to the cells and its K(d) value was 2 orders of magnitude lower than that of the ED50 value for stimulation of cGMP accumulation in the cells. Not only CNP but also ANP displaced [I-125]CNP binding to the cells. These results suggest that RCR-1 cells have a B-receptor which contains a guanylate cyclase domain and is preferentially activated by CNP, and that they also have a C-receptor which does not contain a guanylate cyclase domain that reacts with both ANP and CNP.

高度な気道狭窄のある症例では,術中に換気不能に陥る危険性があり,麻酔管理に当たっては,気道の確保が問題となる.今回,気道狭窄を有する気管腫瘍患者に対する気管形成術に際し,マスクによる補助呼吸下の全身麻酔に部分体外循環を併用することを計画した.術中,偶発的に両側開胸になり,高炭酸血症となったため,体外循環の灌流量を増加させた.しかし,脱血カニューレが左大腿静脈より1本しか挿入されていなかったため,2,000ml/min以上の脱血ができず,気管内挿管による用手的呼吸管理が行なわれるまで,高炭酸血症を改善することは不可能であった.今後は,脱血や送血を十分に確保するために,動・静脈カニューレの本数を増やすことなどを検討する必要があるように思われた.

44歳男.自動車内で意識不明で発見された.衣服はガソリンで濡れており,車内はガソリン臭が強かったが燃えた跡はなかった.広範な皮膚びらんがあり近医にて全身熱傷と診断された.びらんは体表面積の約50%であった.来院時には代謝性アシドーシス,CPK値の異常高値を示した.集中治療にもかかわらず多臓器不全で受傷後9日目に死亡した.吸収されたガソリンは代謝されず,肺からの呼出が主な排泄経路である.しかも呼出時に血管内皮を傷害し,呼吸器合併症を生じる