Effects of halogenated anesthetics on splanchnic hemodynamic in normo- and hypovolemic cirrhotic rats]

The effects of 1 MAC of either halothane, enflurane or isoflurane on splanchnic haemodynamics were studied in cirrhotic rats that were either normovolaemic or hypovolaemic from haemorrhage. A group of conscious rats acted as the control group. Bile duct ligation had been carried out in all the rats four weeks previously to induce cirrhosis. At the time of the study, all the rats were anaesthetized with ether for catheterization of the left femoral artery and vein, and the left ventricle via the right carotid. The control group was allowed to awake. When the other rats started to recover, they were artificially ventilated with room air and 1 MAC of the halogenated agent. Heart rate and mean arterial blood pressure were monitored continuously. Once the animals had remained steady for one hour, 1.25 ml of blood for 100 g body weight was removed over a 10 min period. PaO2, PaCO2, arterial pH, heart rate, mean arterial blood pressure, cardiac index and regional blood flows (RBF) were measured before, and thirty minutes after the haemorrhage. Cardiac output and RBF were measured using the radioactive-labelled microsphere method. Only 32 animals were finally included, eight in each group. Splanchnic, portal and hepatic arterial blood flows were similar in conscious rats and in those receiving isoflurane or halothane, and were higher than in those receiving enflurane. The lowest splanchnic and portal venous blood flows were found in those rats receiving enflurane. After haemorrhage, these RBF decreased significantly in all groups except in the enflurane group.(ABSTRACT TRUNCATED AT 250 WORDS)     

门静脉动脉化加门腔分流对肝硬化大鼠肝储备功能的影响

目的研究入肝门静脉动脉化加门腔分流术对肝硬化大鼠肝脏储备功能的影响。方法 100只肝硬化大鼠随机分为A组（n=40）,入肝门静脉完全动脉化＋门腔分流;B组（n=40）,仅行门腔完全分流;C组（n=20）,门静脉阻断30min＋右肾切除。分别检测术前和各组大鼠术后1周、2周、4周及8周动脉血酮比（AKBR）及吲哚氰氯15min潴留率（ICGR15）。结果术后A组大鼠的AKBR较术前及B、C两组均有明显升高,差异有明显统计学意义（P〈0.01）,并于术后2周,可达到稳态;术后A组大鼠ICGR15较术前及B、C两组明显降低,差异也有统计学意义（P〈0.01）,并于术后2周可达到稳态。结论入肝门静脉动脉化能明显促进肝硬化大鼠肝脏储备功能恢复,有助于预防门腔分流术后肝衰竭。     

二氧化碳气腹对肝硬变大鼠肝功能影响的实验研究

目的 探讨二氧化碳(CO2)气腹对肝硬变大鼠肝功能的影响及可能机制.方法 制作大鼠肝硬变模型,建立不同压力、不同持续时间气腹,于术前、术后检测肝功能、内毒素、丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)、一氧化氮合酶(NOS)含量.HE及免疫组化观察肝组织学变化.结果 (1)气腹压力越高、持续时间越长丙氨酸转氨酶(ALT)、门冬氨酸转氨酶(AST)、内毒素、MDA、NO、NOS则越高,术后组显著高于术前及假气腹组(P<0.05);白蛋白(ALB)在第7天有下降趋势,但无显著差异.(2)NO、NOS、ALT、AST的变化与内毒素变化成正相关(r=0.56、0.57、0.41、0.44,P<0.05).(3)HE及免疫组化显示气腹压力越高、持续时间越长诱生型一氧化氮合酶(iNOS)表达越多,肝组织损害越重.结论 肝硬变条件下,CO2气腹对肝功能的损害与内毒素、NO的异常升高有关.     

Effects of volatile anesthetics on cardiac ion channels

The focus of the present review is on how interference with various ion channels in the heart may be the molecular basis for cardiac side-effects of gaseous anesthetics. Electrophysiological studies in isolated animal and human cardiomyocytes have identified the L-type Ca(2+) channel as a prominent target of anesthetics. Since this ion channel is of fundamental importance for the plateau phase of the cardiac action potential as well as for Ca(2+)-mediated electromechanical coupling, its inhibition may facilitate arrhythmias by shortening the refractory period and may decrease the contractile force. Effective inhibition of this ion channel has been shown for clinically used concentrations of halothane and, to a lesser extent, of isoflurane and sevoflurane, whereas xenon was without effect. Anesthetics furthermore inhibit several types of voltage-gated K(+) channels. Thereby, they may disturb the repolarization and bear a considerable risk for the induction of ventricular tachycardia in predisposed patients. In future, an advanced understanding of cardiac side-effects of anesthetics will derive from more detailed analyses of how and which channels are affected as well as from a better comprehension of how altered channel function influences heart function.     

Effects of volatile anesthetics on cardiac calcium channels

In order to investigate how volatile anesthetics affect cardiac calcium channels, the effects of halothane, enflurane, and isoflurane on the specific binding of [3H]-nitrendipine to bovine heart sarcolemmal membranes were studied. All three anesthetics added in liquid form inhibited [3H]-nitrendipine binding in a dose-dependent manner, and more interestingly, the order of inhibition by these volatile anesthetics roughly followed that of their anesthetic potencies. The partial pressures, calculated using the gas/water partition coefficients of halothane, enflurane, and isoflurane which inhibited [3H]-nitrendipine binding by 30% at 37 degrees C were about 1.48 x 10(-2) atm. (1.48%), 4.89 x 10(-2) atm. (4.89%) and 2.76 x 10(-2) atm. (2.76%), respectively. One mmol/l halothane altered not only the maximal binding (Bmax) from 189 f mol/mg protein to 136 f mol/mg protein, but also the dissociation constant (Kd) from 0.074 nmol/l to 0.18 nmol/l. Halothane was also added to the reaction mixture in the gaseous form with air. The partial pressure of halothane needed to bring about 30% inhibition was 0.82 x 10(-2) (0.82%), a value almost similar to that for halothane added in the liquid form. These results indicate that all three volatile anesthetics have direct effects on cardiac calcium channels, and that the magnitude of the effects depends on their anesthetic potencies.     

Hepatic circulation and oxygen supply-uptake relationships after hepatic ischemic insult during anesthesia with volatile anesthetics and fentanyl in miniature pigs

The objective of the present study was to quantitate the effects of several anesthetics on hepatic circulation, oxygenation, and function after hepatic ischemic insult and during reperfusion. We examined the effects of different anesthetics on hepatic circulation, oxygenation, and function after hepatic ischemic insult in 28 miniature pigs weighing 20-27 kg. The preparation allowed a stepwise decrease followed by a complete cessation for 1 h of hepatic blood and oxygen supply. Immediately after the unclamping of both vessels supplying the liver and restoration of the hepatic circulation, systemic mean arterial pressure decreased to approximately 75% of preischemic values in animals anesthetized with pentobarbital and fentanyl and to 60% of preischemic values in pigs anesthetized with halothane, enflurane, or isoflurane. Total hepatic blood flow immediately returned to preischemic values without significant difference between the groups. Subsequently, hepatic oxygen delivery returned to 75%-95% of preischemic values. Hepatic oxygen uptake returned to 50%-60% of preischemic values in animals anesthetized with pentobarbital and with volatile anesthetics and up to 80% and then later to baseline values with fentanyl anesthesia. Lactate uptake by the liver returned to preischemic values only in animals given fentanyl or isoflurane but remained at approximately 50% of preischemic values during enflurane and 20%-40% during halothane and pentobarbital anesthesia. Thus, the study indicates that both isoflurane and fentanyl anesthesia provide more protection from ischemic insult than do halothane, enflurane, or pentobarbital anesthesia.     

肝门阻断对肝硬化大鼠肠黏膜屏障的影响

目的 探讨肝硬化大鼠肝门阻断后肠道黏膜屏障结构和功能的改变.方法 40 只肝硬化模型雄性SD 大鼠被随机分为假手术组、肝门阻断10 min、肝门阻断20 min、肝门阻断30min 组,每组各10 只.在行肝门阻断术后18 h 乳果糖、甘露醇混合液灌胃,6 h 后收集尿液,检测乳果糖和甘露醇排出率及比值（L/M）,并于术后24 h 取未段回肠行病理组织学和电镜检查.结果 肝硬化大鼠肝门阻断10 min 时即出现明显小肠病理损伤,电镜下可见小肠微绒毛肿胀、缩短,紧密连结变宽.阻断20 min 时,小肠微绒毛缺失、脱落,细胞器肿胀.阻断30 min 时,可见部分肠黏膜细胞坏死,微绒毛脱落以及紧密连结破坏.肝门阻断10 min 组大鼠的尿中L/M 比值（0.069 ±0.022）明显高于假手术组（0.047 ± 0.016）,并随肝门阻断时间延长增高越明显.结论 肝硬化大鼠肝门阻断后可导制肠道黏膜通透性增加,肠黏膜屏障功能受损.     

Effects of volatile anesthetics on the calcium ionophore A23187-mediated alterations in hepatic flow and metabolism in the perfused liver in fasted rats

Alterations in intracellular calcium homeostasis have been implicated in hepatic injury. Volatile anesthetics modulate the homeostasis of intracellular calcium.
The effects of volatile anesthetics on the hemodynamic and metabolic alterations induced by the calcium ionophore A23187 were studied using isolated liver perfusion in fasted rats. The liver was isolated from 24 hr-fasted male Sprague-Dawley rats, and perfused through the portal vein at a constant pressure of 1.2 kPa in a recirculating perfusion-aeration system. Halothane, isoflurane and sevoflurane were administered at 2%, 3% and 4.4%, respectively.
All volatile anesthetics maintained basal hepatic flow, reduced oxygen consumption, and transiently enhanced net lactate production. A23187 at initial concentrations of 0.8 to 3.2 μM decreased hepatic flow and oxygen consumption in a dose-de pendent manner, and enhanced lactate production. All anesthetics significantly attenuated the decreases in hepatic flow and oxygen consumption after administration of A23187 at 1.6 μM. None of the anesthetics significantly influenced the A23187-induced enhancement of net lactate production.
Volatile anesthetics may attenuate the hepatic vasoconstriction and oxygen debt induced by intracellular calcium overload.     

挥发性吸入麻醉药对短潜伏期体感诱发电位的影响

目的 选择合适的吸入麻醉药及其浓度，为术中体感诱发电位（SSEP）监测提供参考。方法 60例择期行神经外科手术的患者随机分为三组：安氟醚组、怫氟醚组和地氟醚组。每个患者在清醒和挥发性麻醉药呼气末浓度分别为0．3、0．5、0．75、1．0和1．5MAC时记录正中神经体感诱发电位N13（颈髓）及N20（大脑皮层）。观察皮层电位N20、颈髓电位N13的潜伏期、波幅和中枢传导时间（CCT）的变化。结果 三种吸入麻醉药不改变皮层下电位N13的潜伏期和波幅（P＞0．05）。而皮层电位N20的潜伏期和中枢传导时间（CCT）随安氟醚、异氟醚和地氟醚呼气末浓度的增加，逐渐延长，波幅则下降（P＜0．05）。其中吸入安氟醚在呼出末浓度1．0MAC时有3例患者波形消失，在1．5MAC时共有6例患者波形消失，而异醚和地氟醚呼吸末浓度只在1．5MAC时有3个患者波形消失。结论（1）挥发性吸入麻醉药对SSEP的皮层成分N20波潜伏期和波幅的影响呈浓度依赖性，对皮层下成分N13波影响轻微；（2）在三种吸入麻醉药中，安氟醚对皮层SSEP影响比异氟醚及地氟醚更大，而后者作用相似。术中SSEP监测时，安氟醚在呼气末浓度不大于0．75MAC时是合适的；异氟醚、地氟醚在呼气末浓度不大于1．0MAC时是合适的。     

复方中药对肝硬化大鼠肝组织内皮素-1mRNA表达的影响

目的　研究复方中药对肝硬化大鼠血浆及肝组织内皮素 1(endothelin 1,ET 1)和肝组织ET 1mRNA表达的影响。方法　采用放射免疫法测定血浆和肝组织ET 1水平 ,逆转录多聚酶链反应 (RT PCR)测定大鼠肝组织ET 1mRNA表达水平。结果　模型组血浆 (171 99± 2 7 86pg/ml)和肝组织ET 1(80 4 8± 2 1 4 5 pg/ml)较对照组 (114 33± 17 34pg/ml,5 3 2 5± 13 6 4pg/ml,P <0 0 5 )均显著升高 ,肝组织ET 1mRNA表达也较对照组 (0 4 6 74± 0 10 4 5vs.0 14 13± 0 0 2 97,P <0 0 5 )显著升高。治疗组血浆ET 1(12 9 80± 13 15 pg/ml)和肝组织ET 1mRNA表达 (0 30 4 0±0 0 813)均显著低于模型组 (171 99± 2 7 86 pg/ml,0 4 6 74± 0 10 4 5 ,P <0 0 5 )。而治疗组肝组织ET 1(77 36± 18 2 7pg/ml)与模型组 (80 4 8± 2 1 4 5 pg/ml)相比无显著差异。 结论　复方中药能显著降低肝硬化大鼠肝组织ET 1mRNA的表达及血浆ET 1水平。     

Comparison of the effects of volatile anesthetics on brain glucose metabolism in rats

The objective of this investigation was to compare the effects of the commonly used volatile anesthetics on concentrations of plasma and cerebral glucose and cerebral intermediary metabolites. Fasted male Long-Evans rats were anesthetized with a volatile anesthetic and, after tracheostomy and paralysis, were mechanically ventilated. Each of three groups received one MAC concentration of anesthesia with halothane, enflurane, or isoflurane. At the end of 60-75 min of anesthesia, blood was sampled for arterial blood gas and plasma glucose analysis, and the brain was rapidly sampled and frozen for analysis of energy metabolites. Physiologic variables were maintained as follows: PaCO2 30-40 mmHg, pHa 7.20-7.40, PaO2 greater than 60 mmHg, MAP greater than 60 mmHg, and rectal temperature 37.5-38.5 degrees C. Mean plasma glucose concentrations in the three groups were as follows (muMol/ml +/- SEM): halothane, 7.45 /- .62; enflurane, 6.95 +/- .22; isoflurane, 10.11 +/- 1.00. Mean brain glucose concentrations in the three groups were (muMol/gm wet weight): halothane, 2.04 +/- .20; enflurane, 2.07 +/- .26; isoflurane, 3.04 +/- .31. Plasma and brain glucose levels were significantly increased in the isoflurane group compared to the other two groups (P less than .05) with no differences occurring in the brain/plasma glucose ratio among the three groups. No differences were present between groups in brain lactate, pyruvate, fructose diphosphate, malate, alpha-ketoglutarate, phosphocreatine, or adenine nucleotides. Thus, at one MAC concentration, major differences between volatile anesthetics on brain energy availability are not present, although isoflurane raised cerebral glucose levels.     

Minimum alveolar concentration of volatile anesthetics in rats during postnatal maturation

BACKGROUND: Although neonatal rats have become widely used as experimental laboratory animals, minimum alveolar concentration (MAC) values of volatile anesthetics in rats during postnatal maturation remain unknown. METHODS: We determined MAC values of volatile anesthetics in spontaneously breathing neonatal (2-, 9-, and 30-day-old) and adult Wistar rats exposed to increasing (in 0.1-0.2% steps) concentrations of halothane, isoflurane, or sevoflurane (n = 12-20 in each group), using the tail-clamp technique. MAC and its 95% confidence intervals were calculated using logistic regression and corrected for body temperature (37 degrees C). RESULTS: In adult rats, inspired MAC values corrected at 37 degrees C were as follows: halothane, 0.88% (confidence interval, 0.82-0.93%); isoflurane, 1.12% (1.07-1.18%); and sevoflurane, 1.97% (1.84-2.10%). In 30-day-old rats, the values were as follows: halothane, 1.14% (1.07-1.20%); isoflurane, 1.67% (1.58-1.76%); and sevoflurane, 2.95% (2.75-3.15%). In 9-day-old rats, inspired MAC values were as follows: halothane, 1.68% (1.58-1.78%); isoflurane, 2.34% (2.21-2.47%); and sevoflurane, 3.74% (3.64-3.86%). In 2-day-old rats, inspired MAC values were as follows: halothane, 1.54% (1.44-1.64%); isoflurane, 1.86% (1.72-2.01%); and sevoflurane, 3.28% (3.09-3.47%). CONCLUSION: As postnatal age increases, MAC value significantly increases, reaching the greatest value in 9-day-old rats, and decreases thereafter, and at 30 days is still greater than the adult MAC value.     

The effects of volatile anesthetics on nonadrenergic,noncholinergic depressor responses in rats

The effects of volatile anesthetics on nonadrenergic, noncholinergic (NANC) transmission mediated by calcitonin gene-related peptide (CGRP) are unclear. We studied the effects of isoflurane, halothane, and sevoflurane on NANC depressor responses to electrical spinal cord stimulation in pithed rats whose mean arterial blood pressure was maintained near 120 mm Hg by continuous infusion of methoxamine. Autonomic outflow was blocked by hexamethonium. After 30 min of inhalation of different concentrations of anesthetics, spinal cord stimulation at the lower thoracic level (10 V at 4 Hz; duration, 1 ms) was applied for 30 s to induce a NANC depressor response. Isoflurane at 2% and halothane at 1.5% attenuated NANC depressor responses significantly, whereas isoflurane at 1%, halothane at 0.75%, and sevoflurane at 2% or 4% did not. Volatile anesthetics did not attenuate the release of CGRP after spinal cord stimulation, whereas isoflurane at 2% and halothane at 1.5% significantly inhibited depressor responses to exogenously administered CGRP. Sevoflurane at 4% did not significantly affect CGRP-induced depressor responses. Thus, isoflurane and halothane at large concentrations attenuate NANC depressor responses by attenuating the depressor action of CGRP, not CGRP release. IMPLICATIONS: The anesthetics isoflurane and halothane attenuate nonadrenergic, noncholinergic depressor responses mediated by calcitonin gene-related peptide in the rat without affecting the release of the peptide.     

Effects of volatile anesthetics on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cultures

BACKGROUND: Volatile anesthetics are known to ameliorate experimental ischemic brain injury. A possible mechanism is inhibition of excitotoxic cascades induced by excessive glutamatergic stimulation. This study examined interactions between volatile anesthetics and excitotoxic stress. METHODS: Primary cortical neuronal-glial cultures were exposed to N-methyl-D-aspartate (NMDA) or glutamate and isoflurane (0.1-3.3 mM), sevoflurane (0.1-2.9 mM), halothane (0.1-2.9 mM), or 10 microM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate (MK-801). Lactate dehydrogenase release was measured 24 h later. In other cultures, effects of volatile anesthetics on Ca++ uptake and mitochondrial membrane potential were determined in the presence or absence of NMDA (0-200 microM). RESULTS: Volatile anesthetics reduced excitotoxin induced lactate dehydrogenase release by up to 52% in a dose-dependent manner. At higher concentrations, this protection was reversed. When corrected for olive oil solubility, the three anesthetics offered equivalent protection. MK-801 provided near-complete protection. Ca++ uptake was proportionally reduced with increasing concentrations of anesthetic but did not account for reversal of protection at higher anesthetic concentrations. Given equivalent NMDA-induced Ca++ loads, cells treated with volatile anesthetic had greater lactate dehydrogenase release than those left untreated. At protective concentrations, volatile anesthetics partially inhibited NMDA-induced mitochondrial membrane depolarization. At higher concentrations, volatile anesthetics alone were sufficient to induce mitochondrial depolarization. CONCLUSIONS: Volatile anesthetics offer similar protection against excitotoxicity, but this protection is substantially less than that provided by selective NMDA receptor antagonism. Peak effects of NMDA receptor antagonism were observed at volatile anesthetic concentrations substantially greater than those used clinically.     

Effects of anesthetics on cystometric parameters in female rats

Aim  

The purpose of this study was to evaluate the effect of ketamine, propofol, midazolam and ether on cystometric parameters in rats.     

肝硬变大鼠肝脏缺血再灌注损伤

为比较硬化肝与正常肝在缺血再灌注损伤时的差异和意义。作者采用四氯化碳复制大鼠肝硬变模型,通过大鼠肝脏缺血再灌注损伤模型,检查不同时限大鼠门静脉血内毒素、肝静脉血一氧化氮。结果显示：肝硬变大鼠再灌注时门静脉内毒素水平更高;肝脏ＮＯ合成释放显著增加。作者认为肝硬变时对缺血再灌注损伤反应与正常大鼠不同,可能是肝硬变时对缺血再灌注损伤更敏感,更易发生肝功能衰竭的重要原因。