Biochemical and biophysical changes in guinea pigs after acute head injury.

Animal experiments were set up mainly to derive additional diagnostic data from the study of biochemical changes after acute head injury. In standardized experiments guinea pigs were subjected in groups of 20 to three identical head injuries, each of either 1.0 J or 1.5 J intensity. The trauma was likely to result in a concussion or contusion syndrome similar to that found in man; 40 animals served as controls. During the 60 min after injury observation and measurement of body functions did not reveal signs of a shock-like condition or hypoxaemia in the traumatized animals compared with control animals. Superficial anaesthesia probably did not influence the findings. Temperature and respiration were altered significantly in all the animals receiving head injuries. Blood gas analysis showed a decrease of standard bicarbonate only after the 1.5 J injury but even though hypoxaemia was not present 2,3-diphosphoglycerate values and P50 increased, compared with the control animals. The fall of plasma lipid concentrations reported probably had to be seen as a sympathomimetic effect of the minor (1.0 J) trauma. Of special significance was the increased activity of malate dehydrogenase and aldolase, found only in the blood of severely traumatized animals, as this could serve as an early diagnostic aid for evaluating head injuries.     

头孢曲松钠对豚鼠胆囊收缩功能影响的实验研究

目的研究头孢曲松钠对豚鼠胆囊收缩功能的影响,以更好地指导临床用药。方法将60只豚鼠随机分为四组,A组(空腹对照组)、B组(饱餐对照组)、C组(空腹实验组)和D组(饱餐实验组)。对实验组C组、D组肌肉注射头孢曲松钠,建立头孢曲松钠相关性胆囊模型。造模成功后,对四组豚鼠的胆囊体积、胆汁量、胆汁及血清中胆汁酸、丙氨酸氨基转移酶(ALT)及胆囊收缩素(CCK)含量及胆囊组织中胆囊收缩素A受体(CCK-AR)基因的表达等进行测定。结果 C组和饱餐实验组的胆囊体积均显著高于A组和B组,表明头孢曲松钠可显著增高豚鼠的胆囊体积(P0.05);实验组豚鼠的胆汁量均显著高于对照组(P0.05),表明实验组豚鼠胆囊内出现胆汁淤积。胆汁中实验组豚鼠的胆汁酸水平均显著低于对照组;而血清中实验组豚鼠的胆汁酸水平均显著高于对照组(P0.05),表明实验组胆汁中胆汁酸的浓度出现下降,而血清中胆汁酸的含量则呈上升趋势。实验组豚鼠的ALT含量显著高于对照组豚鼠,表明头孢曲松钠可致豚鼠ALT水平升高。血清及胆囊组织中实验组的CCK水平均显著低于对照组;实验组胆囊组织中CCK-AR mRNA的相对表达量均显著低于对照组(P0.05)。结论头孢曲松钠可降低血清及胆囊组织中CCK的含量,并抑制CCK受体基因的表达,从而减弱胆囊的收缩功能,导致胆囊内出现胆汁淤积,促进结石的形成。为减少此类不良反应的发生,临床上应尽量避免长期、大剂量的使用头孢曲松钠。     

重症急性胰腺炎血流动力学和氧代谢变化的实验研究

目的 观察重症急性胰腺炎(SAP)猪的血流动力学和氧代谢变化特点,为临床治疗提供理论依据。方法 通过向主胰管逆行注入含质量分数为4％牛磺胆酸钠和质量分数为1％胰蛋白酶的生理盐水溶液(1 ml／kg)诱导猪SAP模型(n=8);通过Swan-Ganz导管和心电监护仪,连续监测心率(HR)、中心静脉压(CVP)、平均动脉压(MAP)、肺动脉楔压(PAWP)、平均肺动脉压(MPAP)和心排血量,计算心脏指数(CI);通过对制模前(0 h)和制模后6、12、24及36 h的动脉及混和静脉血的血气分析,计算出相应的全身氧输送(DO2)、氧耗(VO2)和氧摄取率(O2ext),分析上述各指标的变化。结果 制模12 h MAP和CI与0 h比较显著下降(P均<0.05)。动脉氧分压(PaO2)和DO2都有下降的趋势。与0 h比较,PaO2在制模后6 h以后下降显著,DO2在制模后24 h下降最显著(P均<0.05)。VO2和O2ext的走势一致,都在制模后6 h上升至最高水平(P均<0.05),然后一直下降,制模后24 h较6 h差异具有显著性(P均<0.05)。结论SAP时不仅有血流动力学紊乱,而且有氧代谢障碍。SAP导致多器官功能障碍综合征(MODS)的因素可能与VO2和O2ext下降有关。     

Experimental enteric Shigella and Vibrio infections in mice and guinea pigs

A method has been devised for inhibiting the normal enteric flora, permitting long term asymptomatic enteric infections of mice and guinea pigs with streptomycin-resistant strains of Shigella flexneri or Vibrio cholerae. Introduction of a streptomycin-resistant strain of E. coli into the intestinal tract of experimental animals resulted in a rapid elimination of the enteric pathogens studied. No in vitro production of antibiotic substances by this coli strain could be demonstrated. Active and oral passive immunization did not noticeably influence the number of Shigella or Vibrio organisms recoverable from the feces of infected animals.     

Longitudinal study of cardiac electrical activity in anesthetized guinea pigs by contactless magnetocardiography

Guinea pigs (GPs) are used for preclinical evaluation of electrophysiologic effects of new drugs, because their myocytes have human-like action potentials and ventricular repolarization's (VR) ion currents. This study was aimed to assess the reliability of magnetocardiographic (MCG) mapping for longitudinal studies of GP cardiac electrical activity. Eighteen anesthetized GPs were investigated with an unshielded 36-channel MCG instrumentation, at the age of 5 months (268.1 +/- 19 g). Twelve GPs survived and were restudied when 14 months old (595.6 +/- 90.5 g). RR, PR, QRS, QT(peak), QT(end), JT(peak), JT(end) and T(peak-end) intervals were measured from MCG waveforms. Magnetic field (MF) maps, equivalent current dipole (ECD) parameters and current density imaging were also analyzed. A significant prolongation of the PR (p < 0.05) and QRS (p < 0.001) intervals was found at 14 months. Gender-related differences of VR intervals were not significant. P(peak) and QRS(peak) MFs were similar in all animals, while T(peak) MF varied interindividually at 5 months and showed a rotation in some animals, at 14 months. The ECD strengths, measured at the P(peak), QRS(peak) and T(peak) were stronger (p < 0.01) at the age of 14 months than at 5 months. In contrast to findings in Wistar rats, age-related and gender-related differences of MCG VR parameters were not significant in GPs. Further work is necessary to clarify the variability of VR MF observed in healthy GPs.     

Influence of carbon monoxide, hypoxic hypoxia or potassium cyanide pretreatment on acute carbon monoxide and hypoxic hypoxia lethality.

Pre-exposure of mice to 500 or 1000 ppm of carbon monoxide (CO) for 4 hours resulted in a significant decrease in lethality induced by exposure to 2500 ppm of CO 24 hours later. Pre-exposure to CO had no effect on lethality induced by hypoxic hypoxia (low inspired O2 tension) or potassium cyanide (KCN). Pre-exposure to 10% O2 for 4 hours significantly decreased lethality induced 24 hours later by CO or 7% O2 exposures lethality induced 24 hours later by CO or 7% O2 exposures but had no effect on KCN-induced lethality. Pretreatment with a nonlethal dose of KCN had no significant effect on lethality induced 24 hours later by exposure to CO (2500 ppm), 7% O2 or KCN. The alterations in CO lethality were not associated with alterations in carboxyhemoglobin levels. Studies of oxygen consumption and indicators of oxygen delivery to tissues (P50 and red blood cell 2,3-diphosphoglycerate) failed to provide any evidence of pretreatment alteration. Examination of blood lactate, pyruvate and lactate/pyruvate ratios in control and pre-exposed mice after a short exposure to 2500 ppm of CO showed significantly lower lactate and lactate/pyruvate ratios in the pre-exposed mice as compared to controls. These data suggest that animals pre-exposed to 1000 ppm of CO and 10% O2 are less hypoxic than non-pre-exposed animals even through their oxygen delivery system is unchanged.     

Use of cryomicrotomy to study gastric diffusion of amoxicillin in guinea pigs.

Cryomicrotomy has been used as a new technique for removing gastric mucosae from adult guinea pigs for the study of amoxicillin secretion across gastric mucosae. This method allowed a very regular thickness of the removed surface layer of mucosa to be obtained with good reproducibility. Gastric superficial mucosa concentrations and gastric juice concentrations of amoxicillin were determined 1, 2, and 4 h after intramuscular administration (50 mg/kg) in 21 guinea pigs by a microbiological method. No antibiotic was detected in gastric samples at 4 h, except for a low-level mucosal concentration in one animal, thus indicating the short time that amoxicillin is present in gastric samples.     

Hepatic and splanchnic oxygen consumption during acute hypoxemic hypoxia in anesthetized pigs

OBJECTIVE: To compare the hepatosplanchnic oxygen consumption (VO2) with the hepatic and splanchnic VO2 and to calculate the critical oxygen delivery (DO2crit) below which VO2 decreases in the hepatic, splanchnic, and hepatosplanchnic regions in a model of hypoxemic hypoxia. DESIGN: Prospective animal study. SETTING: University research laboratory. SUBJECTS: Anesthetized and ventilated pigs (n = 7). INTERVENTIONS: The right carotid artery was cannulated to measure mean arterial pressure. A pulmonary artery catheter was inserted to measure mean pulmonary arterial pressure and cardiac output. After a midline abdominal incision, two flow probes were positioned around the portal vein and the hepatic artery to measure portal vein blood flow and hepatic artery blood flow. Oxygen and lactate contents in the carotid artery, the portal vein, and the hepatic vein were measured in blood samples obtained from the appropriate catheters. MEASUREMENTS AND MAIN RESULTS: After a 2-hr stabilization period, hemodynamic and biological variables were recorded during acute hypoxemic hypoxia (FIO2 = 0.5, 0.4, 0.3, 0.21, 0.15, 0.10, and 0.07). VO2, DO2, and DO2crit were determined in the hepatic, splanchnic, and hepatosplanchnic regions. The hepatosplanchnic VO2 was 48 +/- 5 mL/min at high FIO2 (40% for the liver and 60% for the splanchnic organs) and decreased below FIO2 of 0.15. Lactate uptake in the whole hepatosplanchnic region remained steady at FIO2 values of 0.5 to 0.15 and then switched to a lactate release at low FIO2. However, the splanchnic region released lactate, whereas lactate was taken up by the liver. DO2crit in the hepatic, splanchnic, and hepatosplanchnic regions was 24 +/- 3, 38 +/- 2, and 49 +/- 4 mL/min, but the systemic DO2crit, below which regional VO2 became oxygen supply dependent, did not differ in the liver, splanchnic, and hepatosplanchnic regions. CONCLUSIONS: The variables of oxygenation and lactate flux measured in the hepatosplanchnic region summarize the metabolic changes of various organs that may vary in different ways during hypoxemic hypoxia.     

中药皮肤剥脱剂对豚鼠皮肤损伤的实验研究

目的化学药物损伤皮肤后很容易留下瘢痕,自拟中药皮肤剥脱剂在避免化学药物损伤皮肤中的作用,为临床应用提供实验依据。方法将药物外用于豚鼠皮肤,观察不同时间、不同药物对豚鼠皮肤的损伤。结果3d后中药皮肤剥脱剂组对豚鼠皮肤损伤达(0.22±0.06)mm(棘细胞和真皮乳头层);贝克-戈登液组损伤达(0.53±0.03)mm(真皮网状层);杰森液组损伤达(0.10±0.02)mm(角质浅层);低浓度中药皮肤剥脱剂组损伤达(0.12±0.03)mm(角质层)。中药皮肤剥脱剂和贝克液组角质蛋白均出现凝固、坏死、真皮上中层胶原纤维发生重新排列,真皮网状层有中性粒细胞、巨噬细胞、淋巴细胞等炎性细胞浸润;基质对照组未见皮肤损伤。结论中药皮肤剥脱剂优于低浓度中药皮肤剥脱剂和化学剥脱剂,既能控制深度,避免太深引起瘢痕,又能加速表皮死亡细胞或受损细胞的脱换率。     

Nephropathy produced by forssman antibody in guinea pigs:

In the present work the involvement of the kidneys of guinea pigs injected with rabbit anti-sheep red blood cell antiserum (Forssman antibody) was studied. The antibody was introduced by a catheter into the abdominal aorta close to the openings of renal arteries. Glomerular lesions were observed 6 h following the injection: increased cellularity at the expense of polymorphonuclear and mononuclear cells, widened mesangial regions, deposits of fuchsinophilic material in the mesangium and capillary loops. By immunofluorescence the antibody was detected in the mesangial region extending to adjacent capillary loops, but it was not possible to demonstrate the presence of complement with certainty. The presence of subepithelial nodules on the glomerular basement membrane and deposits in the mesangium was demonstrated by electron microscopy. These findings suggest that this glomerulopathy induced by Forssman antibody may be a simple and reproducible model for the study of mesangial lesions.     

游泳增强川芎嗪对慢性低氧豚鼠耳蜗微循环障碍的治疗作用

目的观察游泳锻炼对慢性低氧豚鼠耳蜗微循环的影响。方法将28 只豚鼠随机分成舱外正常对照组(A组,5 只)与慢性低氧模型组(B)。4周后,慢性低氧模型组又随机分为低氧对照组(B1组,5只)、低氧药物(川芎嗪)治疗组(B2 组,8 只)和低氧药物治疗配合游泳锻炼组(B3组,10只)。豚鼠喂养8周后,用激光多普勒(LDF)统计耳蜗血流量(CBF),用螺旋韧带铺片光镜观察豚鼠血管纹毛细血管的形态及血管内红细胞计数。结果A组CBF为(98. 075±5 .08)%,B1 组为(86 .80±2. 12)%(P<0. 01);B2组CBF为(89. 14±4 .12)%,与B1 组有显著性差异(P<0. 05);B3 组CBF为(91 .18±5. 02)%,与B2 组无显著性差异(P>0. 05),但与B1组有非常显著性差异(P<0 .01)。结论游泳锻炼能促进川芎嗪改善慢性低氧环境下豚鼠耳蜗毛细血管的肿胀及红细胞淤滞现象。     

Autogenic thymocytotoxic IgG antibody in normal guinea pigs.

Normal guinea pig serum (GPS) was confirmed to be cytotoxic for guinea pig thymocytes at 4 degrees C. Approximately 50% of the cells were sensitive for the cytotoxic action of GPS (4 h incubation). Binding of IgG and, to a smaller extent, IgM to the thymocyte surface was shown after incubation with GPS. Absorption of GPS with protein A agarose (which removes immunoglobulins), heat inactivation (56 degrees C, which removes complement activity) or treatment with 2-mercaptoethanol (2-me) (which affected binding of IgG and IgM to thymocytes) abolished the cytotoxic activity. After gel filtration chromatography with Sephadex G-150, the cytotoxic activity was found in fractions with molecular weights comparable to that of IgG. This is different from reports of others on natural thymocytotoxic antibodies (NTA) where IgM was found to be the dominant thymocytotoxic antibody. The toxic activity in GPS was readily absorbed by autogenic bone marrow, spleen, lymph node and thymus cells. In contrast to normal thymocytes, mitogen stimulated thymus cells were totally resistant to the cytotoxic activity. In summary, it is suggested that the thymocytotoxic activity in GPS at 4 degrees C is mediated by IgG and complement and is directed against immature thymocytes. The antigenic determinant is also present on cells in other lymphoid organs.     

Comparative pharmacokinetics of aminoglycoside antibiotics in guinea pigs.

The pharmacokinetics of netilmicin, gentamicin, and tobramycin in plasma and in perilymph of guinea pigs were studied after a single intravenous injection of 40 mg/kg. Detailed pharmacokinetic analysis of the plasma drug concentration-time data up to 36 h after the intravenous dose revealed that the pharmacokinetics of the aminoglycoside antibiotics can be best described as a three-compartment open model. The disposition half-lives (t1/2) in plasma of the three antibiotics were comparable and within the following ranges: t1/2 alpha of 0.09 to 0.16 h; t1/2 beta of 0.88 to 1.01 h; and t1/2 gamma of 7.87 to 8.29 h. The volume of distribution in the central compartment and the total body clearance of netilmicin (294 ml/kg, 5.74 ml/min per kg) were greater than those of gentamicin (160 ml/kg, 3.40 ml/min per kg) and tobramycin (204 ml/kg, 4.63 ml/min per kg). Pharmacokinetic analysis of the perilymph drug concentration-time data indicated that all three antibiotics penetrated the perilymph readily, but netilmicin cleared from the perilymph compartment faster than gentamicin and tobramycin. The maximum perilymph drug concentrations were 4.17, 8.05, and 6.78 micrograms/ml and occurred at 1, 2, and 4 h for netilmicin, gentamicin, and tobramycin, respectively. The ratio of area under the curve of perilymph to plasma was lowest for netilmicin (0.27), followed by gentamicin (0.39) and tobramycin (0.57). These results suggest that the differences in pharmacokinetics and concentrations of netilmicin in the perilymph may account for less ototoxic liability of netilmicin compared with gentamicin and tobramycin.     

瘦素预处理减轻小鼠心肌缺血/再灌注损伤的实验探讨

目的 监测小鼠心肌缺血/再灌注损伤(MIRI)过程中,血清炎性细胞因子TNF-α、IL-6水平, 中性粒细胞活性及氧自由基含量的变化,以及瘦素(leptin)预处理对其影响, 探讨瘦素预处理在小鼠MIRI过程中的作用及其机制.方法 24只雄性C57BL/6小鼠随机分为四组:①假手术组;②心肌缺血/再灌注模型组(MIRI组);③MIRI瘦素预处理组(leptin+MIRI组);④MIRI术后瘦素处理组(MIRI+leptin组).在MIRI手术后6 h,四组小鼠分别取标本, 测定小鼠血清炎性细胞因子水平(TNF-α、IL-6)、髓过氧化物酶活性(MPO)水平、血清丙二醛(MDA)活性以及超氧化物歧化酶(SOD)含量.结果瘦素预处理可降低细胞因子TNF-α、IL-6的水平,降低小鼠MPO活性,减少MDA含量并升高SOD活性.结论 瘦素预处理可减少中性粒细胞的聚集与浸润, 减轻脂质过氧化和自由基损伤, 对MIRI有保护作用.     

Cerebral and systemic amino acid metabolism in experimental acute amphetamine poisoning in guinea pigs

Protein catabolism, as measured by plasma amino acids is increased by amphetamine injection (15 mg/kg body wt) administered to 10 adult male guinea pigs. Changes in the cerebrospinal fluid were less marked than those in the plasma. The amphetamine seemed to inhibit the enzymes of the metabolic pathways that use amino acids.     

组织多普勒成像在急性心肌缺血心功能异常中的实验研究

目的 运用组织多普勒成像（TDI）技术对急性心肌缺血区域和二尖瓣环侧壁处的运动速度、移动振幅进行检测,探讨TDI在急性心肌缺血、心肌梗死中的应用价值。方法 10只开胸猪结扎左冠状动脉前降支（LAD）,通过TDI技术速度模式检测缺血区域和心尖四腔观二尖瓣环侧壁处的色泽变化及收缩、舒张期运动速度（VS,VE,VA）、移动振幅（CD,MDe,MDa）、等容收缩期时间,并与基础状态对照分析。结果 LAD结扎后,缺血区域和二尖瓣环处色泽暗淡,局部心肌色彩缺失,结扎15s时收缩期、舒张早期运动速度、移动振幅显著降低,等容收缩期时间延长。结论 TDI技术能准确反映血梗死区域运动异常,精确测定局部收缩、舒张期运动速度、移动振幅,尤其二尖瓣环处的运动能反映整体心肌的运动,为临床早期评价局部心肌缺血及心功能异常提供了一种无创性的检查手段。     

Bronchodilator action of inhaled nitric oxide in guinea pigs.

The effects of inhaling nitric oxide (NO) on airway mechanics were studied in anesthetized and mechanically ventilated guinea pigs. In animals without induced bronchoconstriction, breathing 300 ppm NO decreased baseline pulmonary resistance (RL) from 0.138 +/- 0.004 (mean +/- SE) to 0.125 +/- 0.002 cmH2O/ml.s (P less than 0.05). When an intravenous infusion of methacholine (3.5-12 micrograms/kg.min) was used to increase RL from 0.143 +/- 0.008 to 0.474 +/- 0.041 cmH2O/ml.s (P less than 0.05), inhalation of 5-300 ppm NO-containing gas mixtures produced a dose-related, rapid, consistent, and reversible reduction of RL and an increase of dynamic lung compliance. The onset of bronchodilation was rapid, beginning within 30 s after commencing inhalation. An inhaled NO concentration of 15.0 +/- 2.1 ppm was required to reduce RL by 50% of the induced bronchoconstriction. Inhalation of 100 ppm NO for 1 h did not produce tolerance to its bronchodilator effect nor did it induce substantial methemoglobinemia (less than 2%). The bronchodilating effects of NO were additive with the effects of inhaled terbutaline, irrespective of the sequence of NO and terbutaline administration. Inhaling aerosol generated from S-nitroso-N-acetylpenicillamine also induced a rapid and profound decrease of RL from 0.453 +/- 0.022 to 0.287 +/- 0.022 cmH2O/ml.s, which lasted for over 15 min in guinea pigs broncho-constricted with methacholine. Our results indicate that low levels of inhaled gaseous NO, or an aerosolized NO-releasing compound are potent bronchodilators in guinea pigs.     

Tachykinin receptor antagonists inhibit hyperpnea-induced bronchoconstriction in guinea pigs.

We tested the hypothesis that hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH) are mediated through stimulation of NK-1 and NK-2 receptors in guinea pigs. We first established the efficacy and selectivity of (+/-) CP-96,345 (3 mg/kg i.v.) and of SR-48,968 (300 micrograms/kg i.v.) as NK-1 and NK-2 antagonists, respectively. (+/-) CP-96,345 substantially attenuated bronchoconstriction and systemic vascular leak caused by administration of Sar9,Met(O2)11-Substance P (a specific NK-1 agonist), but had no effect upon bronchoconstriction induced by selective NK-2 stimulation with Nle10-Neurokinin A[4-10]. Conversely, SR-48,968 antagonized the bronchoconstrictor response to Nle10-NKA[4-10], right-shifting the dose-response curve by 2 log units, but had no effect on Sar9, Met(O2)11-SP-induced bronchoconstriction. Anesthetized, tracheostomized, opened-chest male Hartley guinea pigs were pretreated with (+/-) CP-96,345 (3 mg/kg i.v.), SR-48,968 (300 micrograms/kg i.v.), or their respective vehicles, and Evans blue dye (30 mg/kg i.v.) to label circulating albumin. 10 min isocapnic dry gas hyperpnea (12 ml/kg, 150 breaths/min) provoked HIB and HIBVH in vehicle-treated animals. (+/-) CP-96,345 reduced the magnitude of HIB by one-half (peak posthyperpnea RL 7.8 +/- 1.9 [SE] times prehyperpnea baseline versus 16.1 +/- 2.6, vehicle-treated; P < or = 0.0001, ANOVA); SR-48,968 blocked HIB more completely (peak posthyperpnea RL 5.1 +/- 1.7 [SE] times prehyperpnea baseline versus 19.3 +/- 2.8, vehicle-treated; P < 0.0001, ANOVA). Neither drug reduced HIBVH. We conclude that dry gas hyperpnea causes bronchoconstriction in guinea pigs through activation of tachykinin receptors. The differential effects of neurokinin receptor blockade on HIB and HIBVH demonstrate that hyperpnea-induced airflow obstruction is not primarily a consequence of hyperpnea-induced bronchovascular leak.