THE EFFECT OF COLLOID CONCENTRATION ON THE FUNCTIONAL CHARACTERISTICS OF ISOLATED PERFUSED RAT LIVER

The volume of bile produced by isolated perfused rat liver was dependent on the concentration of bovine serum albumin (BSA) in the perfusate, the lowest volumes being obtained with Krebs Ringer bicarbonate (KRB) alone and with 70 g/l. BSA In KRB. Increasing amounts were produced as the concentration of BSA was reduced from 70 g/l. to 8.5 g/l. The concentration of bile salts in the bile decreased rapidly during the first hour, but much more slowly thereafter. The highest concentration observed during the first hour was with KRB alone and the lowest with 20 g/l. BSA; subsequently, the highest concentrations were obtained with 70 g/l. BSA and the lowest with 20 g/l. BSA. Urea synthesis was lowest with KRB alone, but increased as the concentration of BSA increased; however, values obtained with 8.5, 20, and 40 g/l. were fairly close together. With KRB alone there was a rapid release of potassium during the first hour, but thereafter the rate of release was similar to that found when BSA was present. The lowest concentrations of potassium were obtained with 20 and 40 g/l. BSA. With KRB alone, GOT was released from the start of perfusion of 300 units per minute. With BSA present, GOT release was delayed 4 hours, and thereafter the rate was dependent on the concentration of BSA, being lowest with 20 and 40 g/l. (200 units per min), higher with 8.5 g/l. (350 units per min) and highest with 70 g/l. (400 units per min).     

HEPATOTOXICITY TESTING OF ATRACURIUM AND LAUDANOSINE IN THE ISOLATED, PERFUSED RAT LIVER

The pharmacokinetics of atracurium, which is degraded by Hofmanndecomposition and ester hydrolysis, is not altered by impairedliver function. Atracurium should, therefore, be ideal for patientswith hepatic failure, and is now widely used in clinical practice.However, some studies reported considerable hepatotoxicity afteratracurium, especially from its breakdown products–forexample, leakage of lactate dehydrogenase (LDH) from isolatedrat hepatocytes. Therefore, we have studied, in an isolatedperfused rat liver model, biochemical and morphological changesafter administration of either atracurium or its main metabolite,laudanosine. Despite using extremely high concentrations ofthese substances, we could not detect, biochemically (releaseof LDH or aspartate amino-transferase (AST)) or histologically,any signs of liver cell damage.     

体外肝脏切除术对肝脏功能和结构的影响

方法:正常家猪13头，在体外静脉转流和4℃EuroCollins液持续灌注肝脏下行体外肝切除及自体残肝原位再植术。在手术中不同时相点检测肝组织能荷水平（EC）、线粒体呼吸活性（RCR）、动脉血酮体比值（AKBR）和肝脏病理变化。结果：在肝脏冷灌注时相，两组动物肝组织ATP、EC及AKBR水平较术前显著降低，RCR轻度降低。残肝植入后，术程平稳的6头动物，EC水平回升、RCR无显著变化、AKBR回升到0．7以上；术程不平稳的7头动物，RCR下降、EC进一步降低、AKBR仍低于0．5。冷灌注时肝脏组织结构基本保持完整，残肝再植复流后肝组织出现以肝腺泡第Ⅲ带为著的组织损害。结论：体外肝切除术造成肝脏损害的主要原因是再灌流损害；肝细胞能量代谢状态与手术动物的预后密切相关。     

EFFECTS OF MIDAZOLAM ON INSULIN SECRETION FROM ISOLATED RAT PANCREATIC ISLETS OF LANGERHANS

Isolated, cultured rat pancreatic islets of Langerhans wereincubated in medium containing glucose 2 or 20 mmol litre^-1and with glucose supplemented with midazolam 10, 100 or 1000ng ml^-1. Glucose 20 mmol litre^-1 with the addition of noradrenaline10 fimol litre^-1 was used as a control. In contrast with noradrenaline,midazolam did not inhibit glucose-induced insulin secretion.Noradrenaline 10 fimol litre^-1 inhibited secretion to basalvalues in response to glucose 20 mmol litre'1 (Y 0.001). (Br. J. Anaesth. 1993; 70: 221-222) Hormones: insulin. Hypnotics,benzodiazepines. midazolam Midazolam facilitates the effectof the inhibitory neurotransmitter y-aminobutyric acid (GABA).In a recent clinical study [1], circulating concentrations ofinsulin were found to be decreased significantly after inductionof anaesthesia with midazolam 0.42 mg kg^-1 over 5 min; a controlgroup of patients received a sleep dose of thiopentone, afterwhich serum concentrations of insulin were unchanged. Benzodiazepinereceptors have been demonstrated in rat pancreatic tissue [2]and GABA has been found in both rat and human pancreatic islets[3], although at present there is no consensus on the effectsof GABA agonists on the insulin secretory response [4]. It wassuggested [1] that a possible cause of the decrease in seruminsulin concentrations seen clinically after midazolam couldbe direct inhibition of insulin secretion. In this study, wehave investigated the effects of midazolam on glucose-stimulatedinsulin secretion from isolated rat pancreatic islets in vitro.     

海藻酸钠-氯化钡微囊对大鼠胰岛体外胰岛素分泌功能的影响

目的　观察海藻酸钠 -氯化钡微囊对大鼠胰岛体外胰岛素分泌功能有无影响。方法　以海藻酸钠和氯化钡为材料 ,采用气体吹喷制囊法将新鲜分离纯化的大鼠胰岛制成微囊化胰岛 ,取空微囊、微囊化大鼠胰岛与未微囊化大鼠胰岛各 5 0 0只 ,分为 10份 ,置于培养板中培养 ,用放免法测定并比较第 2、4、6 d培养液中基础胰岛素浓度。结果　空微囊组第 2、4、6 d的基础胰岛素平均浓度均为 0 nm ol/ 1/ 5 0 ,微囊化大鼠胰岛组第 2、4、6 d的基础胰岛素平均浓度为 5 .179、5 .80 6、5 .5 5 8nm ol/ 1/5 0只 ,未微囊化大鼠胰岛组第 2、4、6 d的基础胰岛素平均浓度为 5 .4 4 1、6 .0 80、5 .4 6 8nmol/ 1/ 5 0只 ,后两者差异无显著性意义 (P>0 .0 5 )。结论　海藻酸钠 -氯化钡微囊对大鼠胰岛体外胰岛素分泌功能无影响     

THE EFFECT OF AGE ON THE SAFETY FACTOR IN NEUROMUSCULAR TRANSMISSION IN THE ISOLATED DIAPHRAGM OF THE RAT

An analysis of neuromuscular transmission has been made in phrenicnerve/diaphragm preparations from male rats aged 30 days or110 days. The amplitude of miniature end-plate potentials wasfound to decrease with age, being 0.969±SEM 0.058 mVat 30 days and 0.510±SEM 0.031 mV at 110 days. Over thesame period, the quantum content of the first end-plate potentialof a train of 40 at 10 Hz, increased from 144.5, SEM+11.1, –10.4to 346, SEM+41.4, –37.0. A corresponding change was observedalso in the average quantum contents of the last 30 end-platepotentials of each train; from 50.6, SEM+ 3.5, –3.2, to138.9, SEM+15.0, –13.6. The safety factor for neuromusculartransmission, calculated from these measured parameters, wasfound at 30 days to be only 70–80% of that at 110 days.It was estimated that the lower safety factor found in youngrats was approximately equivalent to the neuromuscular blockingaction of a dose of, at least, 0.0225 mg/kg of d-tubocurarine.Extrapolation of these results to man would support previousreports of increased sensitivity to d-tubocurarine inneonates.     

MODIFICATION OF THE EFFECTS OF CHLOROFORM ON THE RAT LIVER

Investigations with chloroform anaesthesia in rats pretreatedwith phenobarbitone indicate that the hepatotoxic action ofchloroform is directly related to the activity of the microsomaldrug-metabolizing enzymes. Pretreatment with disulfiram, aninhibitor of the enzymes in man and rats, completely preventsthe hepatotoxicity of chloroform in rats. It would seem thatthe toxic effects of chloroform on the liver are due to toxicmetabolites, the nature of which remains unknown. The enzymesresponsible for the production of the toxins appear to be locatedin the centre of the hepatic acinus.     

阻塞性黄疸术前胆道外引流对肝细胞再生能力的影响

术前胆道外引注对阻塞性黄疸肝切除术后残肝细胞再生能力影响尚不清楚。本实验通过检测能反遇肝细胞再生能力的肝细胞核ＤＮＡ含量,有丝核分型计数（ＭＩ）和增殖细胞核抗原（ＰＣＮＡ）标记指数变化,对胆总管梗阻５天大鼠胆上引流,１、３、５天,然后观察７０％肝切除对残肝细胞再生能力的影响。实验结果表明：胆道外引流对肝细胞再生能力有抑制影响。     

EFFECT OF MEPTAZINOL ON NEUROMUSCULAR TRANSMISSION IN THE ISOLATED RAT PHRENIC NERVE-DIAPHRAGM PREPARATION*

Meptazinol has been shown to have significant effects on neuromusculartransmission in the isolated rat phrenic nerve-diaphragm preparation.The response of the preparation to indirect electrical stimulationwas increased in a concentration-dependent manner by meptazinolhydrochloride 2–32 µg ml^–1. Meptazinol 0.5–2µg ml^–1 antagonized the effects the tubocurarineon this preparation, and in concentrations of 1 µg ml^–1andgreater, potentiated suxamethonium. These effects were similarto those obtained with neostigmine and it was demonstrated thatmeptazinol had significant anti-cholinesterase activity in theconcentrations used. Inhibition of cholinesterase with ecothio-paterevealed a neuromuscular blocking activity of meptazinol inconcentrations as low ^*A preliminary account of some of this work was presented tothe Anaesthetic Research Society, June 31, 1984.     

促肝细胞生长素对肝硬变大鼠部分肝切除后肝再生影响的实验研究

为观察促肝细胞生长素（ｐＨＧＦ）对肝硬变大鼠部分肝切除后肝再生的影响，应用ＩＢＡＳⅡ全自动图像分析仪检测肝硬变大鼠术后肝细胞ＤＮＡ倍体率及肝脏组化染色后各组酶灰度值（ＯＰＴＤＭ）的变化，并通过检测血清谷丙转氨酶（ＳＧＰＴ）及吲哚青绿１５分钟滞留率（ＩＣＧ１５）以了解残肝功能。结果：实验组（Ａ组）３～４倍体肝细胞明显减少，２倍体及多倍体肝细胞明显增多；术后第１天各组酶灰度值无显著差异，第２、５天琥珀酸脱氢酶（ＳＤＨ）和乳酸脱氢酶（ＬＤＨ）明显增高，而碱性磷酸酶（ＡｋＰ）和酸性磷酸酶（ＡｃＰ）则明显减少；Ａ组术后第５天ＳＧＰＴ和ＩＣＧ１５明显降低。本实验结果提示：ｐＨＧＦ不仅能促使肝硬变大鼠肝切除后残肝的再生，而且能够促进再生肝细胞功能成熟及残肝功能的恢复     

胰岛素及丹参对体外培养成纤维细胞影响的实验研究

为了探讨胰岛素、丹参在伤口愈合过程中对胶原合成与分解代谢的影响，应用人胚皮肤培养成纤维细胞，分设胰岛素组、丹参组及对照组，培养２，４和６天，观察细胞的生长情况。成纤维细胞生长曲线显示：胰岛素组高于对照组，对照组高于丹参组。细胞核分裂率三组分别为１９．６０‰，２．５０‰和３．７７‰。扫描电镜观察发现胰岛素组成纤维细胞周围及表面有大量纤维状物，丹参组成纤维细胞表面光滑，仅有少量纤维状物。认为，胰岛素对成纤维细胞增殖和胶原合成有促进作用，而丹参对成纤维细胞增殖和胶原合成则有抑制作用     

IH764—3对肝脏缺血再灌注损伤的保护作用

目的 探讨中药丹参提取的有效单体IH764－3对肝脏缺血再灌注（ischemia reperfusion,I/R）损伤的作用。方法 通过对预先对大鼠I／R模型腹腔注射IH764－3,经测定肝脏内ATP、AMP、ADP含量、肝细胞的能荷、血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、碱性磷酸酶（AKP）、谷胺酰转肽酶（γ－GT）等指标,并观察肝组织超微结构。结果 用药组较单纯I／R组肝组织内ATP含量高,肝脏功能损害轻,肝组织超微结构的损伤减轻。结论 IH764－3对肝脏I／R造成的损伤有明显的预防作用。     

THE EFFECT OF HALOTHANE ON THE ISOLATED CAT HEART

The effect of The effect of halothane on the electrocardiogramrecorded from the isolated perfused cat heart is described.A halothane tension of between 7 and 14 mm Hg produced bradycardia,atrioventricular dissociation, nodal rhythm and finally asystole.Conditions of low oxygen tension and high carbon dioxide tensionproduced ventricular extrasystoles in isolated hearts exposedto halothane. It is suggested that this provides corroborativeevidence for the contention that the ventricular extrasystolesproduced by halothane in cats can occur independently of sympatho-adrenalactivity. Present address: National Nutrition Research Institute, SouthAfrican Council for Scientific and Industrial Research, P.O.Box 395, Pretorin, South Africa     

ISOFLURANE INHIBITS INSULIN SECRETION FROM ISOLATED RAT PANCREATIC ISLETS OF LANGERHANS

We have investigated the effects of isoflurane on insulin secretionin vitro from rat isolated islets of Langerhans and found asignificant, dose-related and reversible inhibition of insulinsecretion. Isoflurane 2% decreased insulin secretion stimulatedby glucose 20 mmol litre^–1 to basal, nonstimulated values.In other studies to identify the stage in the stimulus secretionpathway for insulin at which the anaesthetic may exert an inhibitoryaction, we have stimulated insulin release using glyceraldehydeand a phorbol ester. Insulin se cretion induced by these secretagogueswas also blocked by isofiurane. This suggests that the inhibitoryeffect of the anaesthetic agent may be at a site distal to stimulationof insulin secretion by glyceraldehyde and phorbol esters. (Br.J. Anaesth. 1993; 71: 873–876)      

胆道疾患对肝脏的影响及手术选择

通过对胆道疾患病人的肝脏活检与非胆道疾患病人肝活检对比分析，探讨对肝脏的影响，从而确定哪些胆道疾患必须手术，哪些胆道疾患可以不须手术。并对手术方法选择提出一些看法。     

THE EFFECT OF URETERIC STENTING ON THE FUNCTION AND MORPHOLOGY OF LONG-TERM RAT RENAL ALLOGRAFTS

In the development of a reliable model for chronic rejection in rat renal allografts. the effect of modifying the ureteric anastomosis was tested. Rats. tolerized by pretreatment with two donor blood transfusions under Cyclosporin A. received renal allografts with either sewn or stented ureter. Control groups received isografts or underwent uninephrectomy with insertion of ureteric stents. For the first 6 days after transplantation, serum creatinine and urea values were lower in allograft recipients with stented ureters than in the group with sewn ureters. The method of ureteric anastomosis did not affect the long-term incidence of abnormal function. Allograft morphology was extremely variable from minor to extensive tubular atrophy. interstitial tibrosis. glomerular hypertrophy, focal and segmental glomerulosclerosis as well as vascular changes. Glomerulosclerosis was absent in controls and increased with time in the allografts. Two hundred days after transplantation all allograft recipients with sewn ureters exhibited some glomerulosclerosis, in half of these kidneys more than 25% of glomeruli were affected. Only 33% recipients of allografts with stented ureters exhibited some glomerulosclerosis and less than 20% of glomeruli were affected. The stented ureteric anastomosis provides a reliable method, a reduction of the technical failure rate, a reduction of the incidence of hydronephrosis, allows more accurate assessment of early renal function and may be of importance in reducing the occurrence and prevalence of glomerulosclerosis in the long-term allografts.     

肝硬变门脉高压症及不同术式对大鼠肝脏储备功能的影响

用四氯化碳／乙醇诱导的大鼠肝硬变模型分为４组：①选择性远端脾腔分流术（ＤＳＣＳ）；②门奇断流术（ＰＡＤ）；③肠腔侧侧分流术（ＭＣＳ）和④肝硬变组。在术后１、３、５周进行口服糖耐量试验（ＯＧＴＴ）、胰高糖素负荷试验（ＧＬＴ），比较各组肝脏储备功能的变化。结果表明：术后第１周ＤＳＣＳ、ＰＡＤ和ＭＣＳ与肝硬变组比较无显著性差异（Ｐ＞０．０５）；而术后第３和５周，ＤＳＣＳ和ＰＡＤ组与肝硬变组比较有显著性差异（Ｐ＜０．０５），ＭＣＳ组与肝硬变组比较无显著性差异（Ｐ＞０．０５）。本研究结果表明：ＤＳＣＳ和ＰＡＤ组大鼠肝脏储备功能明显优于ＭＣＳ组和肝硬变组。