Characterization of continuously extruded iopromide-carrying liposomes for computed tomography blood-pool imaging.

RATIONALE AND OBJECTIVES: Contrast-carrying liposomes are potentially useful as computed tomography (CT) blood-pool agents. In the present study, preliminary safety, pharmacokinetics, and the CT imaging behavior of continuously extruded iopromide-carrying liposomes were studied. METHODS: Iopromide liposomes were prepared by continuous high-pressure extrusion. Cell membrane-damaging characteristics were assessed in vitro in dog erythrocytes. Acute and subchronic toxicity and pharmacokinetics parameters were determined in rats. Computed tomography imaging efficiency was studied in rabbits. RESULTS: The iopromide-carrying liposomes caused only minor morphological changes in dog erythrocytes. The median lethal dose in rats was approximately 4.5 g of total iodine per kilogram of body weight. In a subchronic tolerance study in rats that were administered six doses of 1 g iodine per kilogram twice a week, no adverse effects were observed. The pharmacokinetics in rats was dose dependent, and elimination of iopromide was almost complete within 7 days after intravenous administration. In rabbits, at a dose of 300 mg total iodine per kilogram, the iopromide-carrying liposomes displayed prolonged blood circulation, with mean CT density differences > 60 Hounsfield units (aorta) for up to 10 minutes. CONCLUSIONS: The iopromide liposomes were well tolerated, almost completely excreted, and have potential as a CT blood-pool imaging agent.     

吡那地尔预处理对失血性休克大鼠血流动力学影响的实验观察

目的观察吡那地尔预处理（Ｐｒｅｃｏｎｄｉｔｉｏｎｉｎｇ，ＰＣ）对失血性休克大鼠血流动力学的影响。方法复制失血性休克模型前 ２４ 小时，预先给予大鼠 ２次腹腔注射吡那地尔 ２５μg／ｋｇ进行预处理，观察预处理对心率（ＨＲ）、平均动脉压（ＭＡＰ）、左室收缩压（ＬＶＳＰ）、等容收缩压（ＩＰ）、左室压力上升和下降的最大变化速率（±ｄｐ／ｄｔｍａｘ）、实测心肌最大收缩速度（ＶＰＭ）和心肌收缩向量环面积（Ｌｏ）。结果预处理明显增强心功能，ＨＲ、ＭＡＰ、ＬＶＳＰ在观察时相点内较对照组明显提高；反映心肌收缩舒张性能的± ｄｐ／ｄｔｍａｘ、ＶＰＭ和 Ｌｏ各值较 Ｃ组为高。结论吡那地尔预处理能改善失血性休克的血流动力学，减轻失血性休克对大鼠造成的心功能损伤。     

An in vitro study of the hemodynamic effects of catheter injections

The injection jet from a catheter has been shown to elevate distal pressure and flow. These disturbances in flow present a problem for the application of digital arteriography to measure physiologic flow. The authors used an in vitro model to determine the primary factors responsible for the increases in distal flow with the goal that these disturbances might be estimated and minimized. Experiments were performed to evaluate the importance of the cross-sectional area of the catheter and vessel, the importance of absolute vessel flow, and the importance of distal resistance. A lumped resistance model predicted the flow changes to within 3% of the preinjection vessel flow. In the model system the elevation of distal flow in percent was equal to (the injection rate divided by the tube flow rate) multiplied by (the proximal resistance divided by the total resistance) multiplied by 100. Because the resistance ratio generally is small, injections at physiologic flow rates should produce acceptably small increases in distal flow. The use of a large diameter catheter or the presence of a proximal stenotic lesion would increase the ratio.     

Bolus injection of MR contrast agents: hemodynamic effects evaluated by intracerebral laser Doppler flowmetry in rats.

PURPOSETo determine the effects on arterial blood pressure and cerebral blood flow of intravenous bolus injection of three MR contrast agents: gadopentetate dimeglumine, polylysine-Gd-DTPA, and superparamagnetic iron particles (SPIO).METHODSA single-fiber laser Doppler flowmetry probe was placed intracerebrally in 56 anesthetized rats. Cerebral blood flow and mean arterial blood pressure were measured before (baseline), during, and up to 30 minutes after intravenous bolus administration of the three contrast agents: 0.1 mmol/kg and 0.3 mmol/kg gadopentetate dimeglumine (n = 18 per group), 0.3 mmol/kg polylysine-Gd-DTPA (n = 10), and 0.03 mmol/kg SPIO (n = 10).RESULTSNeither the higher nor lower dose of gadopentetate dimeglumine had any statistically significant effect on cerebral blood flow, and there was no change in blood pressure during administration of either dose of gadopentetate dimeglumine. Administration of polylysine-Gd-DTPA caused a transient drop in blood pressure in two animals, marked in one (decrease to 21% of baseline values) and mild in the other (84% of baseline). After administration of SPIO, a significant decrease in blood pressure occurred in one animal (41% of baseline). Despite this decrease in mean arterial blood pressure, there were no statistically significant changes in cerebral blood flow after administration of polylysine-Gd-DTPA or SPIO.CONCLUSIONOur results suggest that bolus injection of these contrast agents at clinically relevant doses causes no significant alteration in cerebral blood flow. We conclude that gadopentetate dimeglumine is well suited for cerebral MR perfusion imaging without inherent influence on cerebral blood flow and that the same is probably true for polylysine-Gd-DTPA and SPIO.     

安多霖对微波辐射致大鼠脑损伤的预防作用研究

目的 探讨安多霖对微波辐射致大鼠脑损伤的预防作用.方法 140只二级雄性Wiser大鼠随机分为5组:健康对照组、辐射对照组、低浓度(0.75 g·kg～·d-1)预防组、中浓度(1.5 g·kg～·d-1)预防组及高浓度(3 g·kg～·d-1)预防组.预防组每日1次灌胃给予安多霖溶液,连续给药工2周.给药结束后采用30 mW/cm.微波辐射大鼠15 min.于处理后6 h、7 d和14 d,采用Morris水迷宫检测大鼠学习和记忆能力,高效液相色谱检测海马氨基酸类神经递质含量,光镜和电镜观察海马组织学和超微结构变化.结果 微波辐射后7 d内,大鼠学习和记忆能力下降(F=0.000～0.043,P<0.05);微波辐射后6 h,4种氨基酸类神经递质含量均降低,其中谷氨酸、甘氨酸及γ-氨基丁酸降低明显(F=0.000～0.007,P<0.01);微波辐射后6 h、7 d,海马组织水肿,神经元变性;神经元线粒体肿胀、空化,内质网扩张,突触间隙模糊,血管周间隙增宽.低浓度预防组上述变化与辐射对照组相似.中浓度和高浓度预防组微波辐射后7 d内,大鼠学习和记忆能力损伤不明显,两者与辐射对照组相比,差异有统计学意义(F=0.015～0.028,P<0.05);微波辐射后6 h,4种氮基酸类神经递质含量均无明显下降,其中谷氨酸含量接近正常,两者与辐射对照组比,差异有统计学意义(F=0.000-0.042,P<0.05);微波辐射后6 h、7 d,海马组织无明显损伤.结论 30 mW/cm.微波辐射可引起大鼠学习和记忆能力下降、海马氨基酸类神经递质代谢紊乱及海马组织学和超微结构损伤;1.5和3 g·kg-1·d-1安多霖对微波辐射致大鼠脑损伤有预防作用.1.5 g·kg-1·d-1安多霖为预防微波辐射致大鼠脑损伤的有效剂量.

Abstract：

Objective To study the prevention effects of AduoLa Fuzhenglin(ADL)Oll the brain injury induced by microwave radiation in rats.Methods A total of 140 male Wismr rats were divided randomly into 5 groups,including control group,microwave exposed group,low dosage(0.75 g·kg-1·d-1)group.middle dosage(1.5 g·kg-1·d-1)group and high dosage(3 g·kg-1·d-1)group.Rats in three ADL groups were lavaged with ADL per day for 2 weeks before radiation.After administration,rats were exposed to microwave at 30 mW/cm2 for 15 min.The abilities of learning and memory were detected by Morris water maze,and the contents of amino acids neurotransmitter of hippocampus were detected by HPLC, then the histology and uhrastrncture of hippocampus were observed with light and electron microscope at 6 h,7 and 14 d after exposure.Results The abilities of learning and memory were declined(F=0.000-0.043,P<0.05)from 6 h to 7 d after exposure,and the contents of four kinds of amino acid neurotransmitter in hippocampus were decreased,of which GLU,GLY and GABA were decreased significantly(F=0.000-0.007,P<0.01)at 6h after exposure,then tissue edema,neuronal degeneration,neuron mitoehondria swelling and cavitation,endocytoplasmie rotieulum broaden,synaptic cleft blurred,and perivascular space widen were found in the hippocampus at 6 h and 7 d after exposure.The changes in low dosage group were similar to those of the radiation group.However,in middle and high dosage groups,the abilities of learning and memory were normal to some extent with the significant differences compared to the radiation group from 6 h to 7 d after exposure(F=0.015-0.028.P<0.05).The contents of four kinds of amino acid neurotransmitter were not decreased,especially GLU contents close tO normal level.There were significant differences between middle and high dosage groups and radiation group at 6 h after exposure(F=0.000-0.042,P<0.05).Moreover,no obvious injury in the hippocampus was observed in middle and high dosage groups at 6 h and 7 d after exposure.Conclusions Exposure to 30 mW/cm2 microwave radiation could decrease the abilities of learning and memory,induce amino acid neurotransmitter turbulence,and injure the histology and uhrastructure of hippocampus.ADL at the dosages of 1.5 and 3 g·kg-1·d-1 would have preventive effects on the injury induced by microwave exposure.The concentration of 1.5 g·kg-1 ·d-1 of ADL might be the effective dosage to prevent the brain damage after microwave exposure.     

安多霖对微波辐射致大鼠脑损伤的预防作用研究

Objective To study the prevention effects of AduoLa Fuzhenglin(ADL)Oll the brain injury induced by microwave radiation in rats.Methods A total of 140 male Wismr rats were divided randomly into 5 groups,including control group,microwave exposed group,low dosage(0.75 g·kg-1·d-1)group.middle dosage(1.5 g·kg-1·d-1)group and high dosage(3 g·kg-1·d-1)group.Rats in three ADL groups were lavaged with ADL per day for 2 weeks before radiation.After administration,rats were exposed to microwave at 30 mW/cm2 for 15 min.The abilities of learning and memory were detected by Morris water maze,and the contents of amino acids neurotransmitter of hippocampus were detected by HPLC, then the histology and uhrastrncture of hippocampus were observed with light and electron microscope at 6 h,7 and 14 d after exposure.Results The abilities of learning and memory were declined(F=0.000-0.043,P<0.05)from 6 h to 7 d after exposure,and the contents of four kinds of amino acid neurotransmitter in hippocampus were decreased,of which GLU,GLY and GABA were decreased significantly(F=0.000-0.007,P<0.01)at 6h after exposure,then tissue edema,neuronal degeneration,neuron mitoehondria swelling and cavitation,endocytoplasmie rotieulum broaden,synaptic cleft blurred,and perivascular space widen were found in the hippocampus at 6 h and 7 d after exposure.The changes in low dosage group were similar to those of the radiation group.However,in middle and high dosage groups,the abilities of learning and memory were normal to some extent with the significant differences compared to the radiation group from 6 h to 7 d after exposure(F=0.015-0.028.P<0.05).The contents of four kinds of amino acid neurotransmitter were not decreased,especially GLU contents close tO normal level.There were significant differences between middle and high dosage groups and radiation group at 6 h after exposure(F=0.000-0.042,P<0.05).Moreover,no obvious injury in the hippocampus was observed in middle and high dosage groups at 6 h and 7 d after exposure.Conclusions Exposure to 30 mW/cm2 microwave radiation could decrease the abilities of learning and memory,induce amino acid neurotransmitter turbulence,and injure the histology and uhrastructure of hippocampus.ADL at the dosages of 1.5 and 3 g·kg-1·d-1 would have preventive effects on the injury induced by microwave exposure.The concentration of 1.5 g·kg-1 ·d-1 of ADL might be the effective dosage to prevent the brain damage after microwave exposure.     

The renal hemodynamic response to diatrizoate in normal and diabetic rats

To study the renal hemodynamic response to a large intravenous bolus of a radiocontrast agent, 8 ml/kg body weight of 60% diatrizoate meglumine (D-60) was infused over 30 seconds in both normal rats and rats with streptozotocin-induced diabetes. The effect of equiosmolar mannitol (1350 mOsm/kg) was compared with the D-60 response in normal rats to examine the potential role of hypertonicity in mediating a response. A similar two-phase response was seen in all three groups. The effect of D-60 in normal rats was similar to that of mannitol, but all responses were reduced in diabetic rats. During Phase I in normal rats in response to D-60 there was a transient three-minute reduction in blood pressure (BP), and renal blood flow (RBF) fell by 62 +/- 7%. During Phase II blood pressure did not change from normal baseline values, but RBF fell by 29 +/- 5%; GFR fell by 42 +/- 3%, and filtration fraction (FF) diminished. In diabetic rats baseline FF was lower than normal and was not further reduced after infusion of D-60. It is suggested that D-60 reduces RBF and GFR by a nonspecific osmotic effect, perhaps related to tubuloglomerular feedback or to an acute increase in intratubular pressure. Responses to these mechanisms may be reduced in diabetic rats with a chronic glycosuric osmotic diuresis.     

Peripheral hemodynamic effects of intraventricular and intracoronary contrast media in man

The effects of intraventricular and intracoronary contrast media on the peripheral arterial and venous beds were directly measured with forearm plethysmography. Standard dose intraventricular radiographic contrast produces a potent peripheral arterial vasodilator effect accompanied by a hypotensive and tachycardic response, followed by peripheral venoconstriction, suggesting that the net hemodynamic response is mediated peripherally. Coronary arteriography is associated with a differing pattern of response, suggesting that the most important hemodynamic effects are mediated via myocardial depression with secondary peripheral vascular responses. Hemodynamic changes occur earlier than those following ventriculography and reflect peripheral arterial and venous constriction. Dose and osmolarity of the contrast are important determinants as well as the site of administration.     

The effects of sufentanil on the hemodynamic and respiratory response to exercise

The effects of the potent opioid, sufentanil, were studied in 11 athletes. Sufentanil was administered intravenously (up to 0.5 microgram.kg-1 over 10 min) to the subjects while they ran at 14 km.hr-1 on a level treadmill. Prior to, and after, the drug infusion, the treadmill was inclined by 6% for 4 min and CO2 was inhaled for 4 min. Two groups were studied: group 1 (six subjects) breathed room air and group 2 (five subjects) breathed O2 enriched air. During level running the ventilation (liters.min-1) of the group 1 subjects was reduced (65.3 +/- 8.6 to 55.9 +/- 4.9, P = 0.09, mean +/- standard error) and PaCO2 (mm Hg) increased from 37.6 +/- 0.7 to 44.0 +/- 0.5 (P less than 0.05). PaO2 (mm Hg) was substantially reduced from 92.0 +/- 2.0 to 70.0 +/- 2.0 (P less than 0.05). In group 2, where hypoxia did not occur, ventilation was reduced from 62.5 +/- 1.5 to 47.6 +/- 1.0 (P less than 0.05). The ventilatory response to the CO2 was shifted to the right but the slope was unchanged by sufentanil. The 6% grade did not cause any significant change in the PaCO2 in either group 1 (0.1 +/- 0.4 prior and 0.8 +/- 0.5 mm Hg increase after sufentanil) or group 2 (1.0 +/- 1.5 prior and 0.4 +/- 0.9 mm Hg increase after sufentanil). The heart rate response was unaffected by sufentanil but the blood pressure increase in response to the 6% grade was blocked with the drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

糖尿病大鼠视网膜NF-kB表达与其血流改变的实验性研究

目的:连续6个月,观察NF-kBp65在视网膜的表达,研究糖尿病大鼠视网膜中央动脉、静脉血流动力学的变化,并探讨分析两者的相关性。方法:采用右下腹腔内一次性注射Streptozotocin 60mg/kg诱导Wistar大鼠糖尿病模型35只,分别于成模后1、2、34、、5及6个月,行视阀膜NF-kBp65的免疫组织化学检测、视网膜血管消化铺片和彩色多普勒血流显像检查。结果:NF-kBp65在正常对照组大鼠视网膜的血管层有少许阳性表达,随糖尿病病程延长,NF-kBp65的阳性表达数目和范围增加,同时,视网膜中央动脉速度减低,博动指数、阻力指数增加,视网膜中央静脉流速增加,视网膜微血管出现狭窄闭塞。结论:NF-kBp65的表达随糖尿病病程延长、视网膜组织缺血缺氧的加重而显著增加。     

海水浸泡对失血性休克大鼠血流动力学和一些生化代谢的影响

目的　研究 1 5℃低温海水浸泡对失血性休克大鼠血流动力学和一些生化代谢的影响。方法　采用雄性 Wistar大鼠 ,分为 3组 :正常对照组 (n=8) ;失血性休克组 (n=8) ;海水浸泡失血性休克组 (n=8)。测定血流动力学 ,血乳酸 (L A)、乳酸脱氢酶 (L DH )、磷脂酶 A2 (PL A2 ) ,血液和组织 MDA,分离肝线粒体 ,测定线粒体 H - ATP酶和琥珀酸脱氢酶 (SDH)。结果　海水浸泡失血性休克大鼠血浆L A、L DH、PL A2 、血浆和组织 MDA均显著高于失血性休克组和对照组 ,而血流动力学、肝细胞、心肌细胞线粒体 H - ATP酶和 SDH均显著低于失血性休克组和对照组。结论　 1 5℃海水浸泡失血性休克大鼠伤情明显加重 ,血流动力学减弱 ,缺血再灌流损伤加重 ,线粒体酶及能量合成和分解均下降 ;代谢性酸中毒加重 ,磷脂酶活性升高 ,膜通透性升高     

胆红素对大鼠实验性高脂血症的防治作用

 目的 研究胆红素对大鼠实验性高脂血症的防治作用.方法 将Wister大鼠随机分为对照组、模型组、预防组、治疗组.对照组每日灌胃一般饮用水10 ml/kg,其余各组每日灌胃脂肪乳10 ml/kg,连续灌胃4周.预防组于灌胃脂肪乳第1天开始静脉注射胆红素钠注射液5 ml/kg,两周后治疗组开始静脉注射胆红素钠注射液5 ml/kg,对照组、模型组注射等容积氯化钠注射液.预防组连续注射胆红素钠注射液5周,治疗组注射胆红素钠注射液3周.末次给药后24 h,眼眶取血制备血清,测定血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C).结果 预防组TC、TG、LDL-C均明显低于模型组(P<0.01),预防组TC、TG、LDL-C低于治疗组(P<0.05).结论 胆红素对大鼠实验性高脂血症 TC、TG、LDL-C不但有明显的治疗作用,而且有预防作用,是治疗高脂血症有效的新方法.     

速尿和氨茶碱对小猪再缺氧损伤的预防效果

目的寻找预防缺氧动物吸入纯氧后再损伤的药物。方法15只自平原空运至高原(3658m)的小猪被分为3组：对照组、速尿组和氨茶碱组。采用右心漂浮导管检测法，观察猪吸入纯氧后恢复吸空气前静推氨茶碱或速尿对再缺氧损伤的预防效果。结果对照组动物肺动脉平均压在吸入100％氧气后即明显下降，在突然停止吸氧而改吸室内空气后，下降的肺动脉压逐渐回升，5min后恢复到吸氧前水平。随着时间的延长，肺动脉压继续攀升，15min时肺动脉压达最高点，明显高于吸氧前水平。与此同时，动脉血氧分压较吸氧前低。而当猪在停止吸氧的同时，静推氨茶碱或速尿后，下降的肺动脉平均压虽有所回升，但回升速度明显低于对照组，在停止吸氧30min时，仍低于吸氧前水平。结论猪存在再缺氧损伤，速尿、氨茶碱均可预防缺氧动物再缺氧损伤。     

瑞芬太尼与舒芬太尼抑制患者气管插管血液动力学反应效果的比较

目的比较等效剂量的瑞芬太尼与舒芬太尼抑制患者气管插管血液动力学反应的效果。方法择期腹部手术患者166例,ASAⅠ级或Ⅱ级,年龄18～63岁。随机分为两组：瑞芬太尼组（R组,n=83）和舒芬太尼组（S组,n=83）。麻醉诱导：静脉注射咪达唑仑0．1mg／kg、异丙酚2．5mg／kg、瑞芬太尼1μg／kg（R组）或舒芬太尼0．1μg／kg（S组）、维库溴铵0．1mg／kg,气管插管后机械通气。于麻醉诱导前（基础值）、气管插管前后即刻、气管插管后lmin、3min、5min时记录SP、DP、MAP和HR．观察气管插管反应的发生情况。结果与基础值比较,两组其余时间点血液动力学指标均降低（P〈0．05）,且R组低于S组（P〈0．05）;S组BP和HR最大值较基础值升高,R组较基础值降低（P〈0．05）。结论在复合异丙酚一维库溴铵麻醉诱导时．等效剂量的瑞芬太尼较舒芬太尼抑制患者气管插管血液动力学反应的效果好。