Development of an isolated, pulsatile blood-perfused rat lung model for evaluating the preserved lung functions

The purpose of this study was to develop an isolated, pulsatile blood-perfused rat lung model that allows us to evaluate the preserved lung functions. Lungs isolated from Sprague-Dawley rats, were perfused with venous whole blood by either a pulsatile or constant flow. The effuent was continuously deoxygenated with a 95% N₂/5% CO₂ gas mixture. Airway resistance, lung compliance, elastic work, flow resistive work, pulmonary vascular resistance, and blood gas analysis were assessed. Pressor responses toN ^G -monomethyl-l-arginine (l-NMMA) were compared between pulsatile and constant blood flow. At a flow of 0.1 ml/g body weight/min, pulsatile perfusion allowed for stable perfusion at least for 2h (mean 162.5±15.1 min) with stable aerodynamic and hemodynamic variables including blood gas tensions, whereas constant perfusion resulted in immediate lung failure. Whenl-NMMA was added to the perfusate, the mean pulmonary artery pressure did not show any change in the constant flow (6.0±2.6% increase), but did show a significant increase in the pulsatile flow (45±11% increase). Pulsatile blood flow reduced the pulmonary vascular resistance relative to the constant flow and allowed for a 2-h perfusion period to evaluate the lung function. The vasorelaxant mechanism in the pulsatile perfusion is related in part to the endothelial-dependent relaxation observed in the nitric oxide pathway. Presented in part at the 79th, Annual Clinical Congress of the American College of Surgeons (ACS) held in San Francisco, CA USA, 1993.     

拮氟锐对大鼠肠道氟吸收及微量元素的影响

拮氟锐是由硼、微量元素和中药制成的抗氟药物。本文应用肠道原位灌流技术。观察了拮氟锐对大鼠肠道氟吸收的干预作用及微量元素的影响。结果透明：拮氟锐可促进肠道ＢＦ４的形成，使氟吸收量减少，血氟降低。同时，拮氟锐可拮抗氟所致的微量元素的降低。与硼锌组比较，拮氟锐的抗氟作用效果更明显。     

川芎嗪和参麦注射液对老龄大鼠脑缺血再灌注胃肠损伤的作用

目的 :研究川芎嗪和参麦注射液及其配伍对老龄大鼠脑缺血再灌注胃肠损伤作用。方法 :选SD 2 0～ 2 2月龄大鼠分为对照组、模型组、尼莫通组、川芎嗪组、参麦组、川芎参麦组 ,测各组脑电图幅度的变化 ,胃肠组织、血清、血液和下丘脑中的生化指标及胃肠生理变化。结果 :川芎嗪和参麦注射液对老龄大鼠脑缺血再灌注胃肠组织损伤有明显保护作用。结论 :其保护作用机制与拮抗自由基损伤、调节ATP酶活性和降低肿瘤坏死因子及调节单胺类神经递质的变化有关。川芎嗪和参麦注射液及其配伍的作用机制有所不同     

Effects of different perfusates on functional parameters of isolated perfused dog kidneys.

BACKGROUND: The isolated perfused canine kidney has been established as a valid model for conducting both renal physiology and transplantation research. This model is of particular importance for developing new strategies to improve graft function after renal transplantation. In the present study, a newly developed method using isolated haemoperfused porcine kidneys was adapted for use in canine kidneys. In contrast to haemoperfusion, synthetic perfusion media can be standardized and can prevent the initiation of blood-mediated reperfusion reactions. Thus, an additional aim was to determine whether blood could be replaced by synthetic cell-free perfusion solutions. METHODS: Canine kidneys (n = 30) were harvested from donors euthanized in veterinary practices for causes unrelated to the present study. The kidneys were isolated and perfused with autologous blood or cell-free synthetic electrolyte buffer (Tyrode solution). During perfusion, we monitored renal perfusate flow (RPF), glomerular filtration rate (GFR), electrolyte and glucose reabsorption, oxygen consumption and urine concentration. RESULTS: Changes in perfusion medium did not affect the RPF. In contrast, GFR, urine concentration and oxygen consumption were significantly higher, whereas fractional excretion of sodium and glucose were significantly lower in blood- than in Tyrode-perfused kidneys. CONCLUSIONS: This system offers a simple model for studying whole-organ functional alterations after acute renal ischaemia. Renal function indicators were below values reported during in vivo physiological conditions. These functions were better conserved when kidneys were perfused with autologous blood than with Tyrode.     

小剂量卡介苗、丝裂霉素交替灌注预防浅表性膀胱癌术后复发

目的 观察小剂量卡介苗(BCG)、丝裂霉素C(MMC)交替灌注预防浅表性膀胱癌术后复发的疗效和安全性。方法 回顾性分析自2000年5月～2001年6月的45例浅表性膀胱癌患的临床资料，29例行膀胱部分切除术，16例行经尿道膀胱肿瘤电切术(TuRBt)，术后定期应用卡介苗60mg、丝列霉素C 10mg交替膀胱灌注，每周1次共6次，间歇3个月，再每月1次，持续12个月。其中Ta、T1期22例、T2期23例。结果 所有病人随访12～24个月，45例患中，共有2例复发，均为TURBt后T2病人，总有效率95．2％，无全身不良反应，仅2例应用BCG后出现轻度膀胱刺激症状。结论 小剂量MMC、BCG交替膀胱内灌注，预防浅表性膀胱癌术后复发，效果好、病人耐受性强、副作用小。     

Estimated Functional Diameter of Alveolar Septal Microvessels at the Zone I-II Border

Objective : To measure the functional diameter of alveolar septal microvessels under conditions in which the pulmonary arterial pressure and the lung inflation pressure are equal, at 25 cm H₂O (zone I-II border), and to compare these results with those obtained when inflation pressure exceeded arterial pressure by 5 or 10 cm H₂O (zone I). Methods : We perfused isolated rat lungs (P_A 25, P_PA 25, P_LA 0 cm H₂O) with fluorescent latex particles of specific diameters (0.49, 1.05, 2.0, 4.0, or 10 μm) and then prepared samples for histology. Using a confocal, laser-scanning fluorescence microscope, we measured latex particle densities within the septal plane of individual alveoli. We compared these particle densities with those in arterioles supplying the septa and calculated the density ratio. We fit curves produced by the Verniory equation to these ratios to estimate the septal microvessel functional diameter. Results : Particle densities in septa ranged from 0.06 ± 0.02 particles per μm² ‘for 0.49-μm-diameter particles to 0.007 ± 0.004 particles per μm² for 4.0-μm-diameter particles. The 10-μm particles did not enter septa. Calculations based on these data suggest a septal microvessel functional diameter of 6–8 μm. Conclusions : In a previous study, conducted at the same value of P_inflat, but with P_PA set at 15 or 20 (5 or 10 cm H₂O into zone I), we estimated the capillary diameter to be 1.7 μm. Thus, the septal capillary diameter seems to increase by three- to fourfold as P_PA is raised to equal P_inflat.     

A Correlation Between the Permeability Characteristics of a Series of Peptides Using an in Vitro Cell Culture Model (Caco-2) and Those Using an in Situ Perfused Rat Ileum Model of the Intestinal Mucosa

In an attempt to establish an in vitro/in situ correlation of intestinal permeability data, the permeability coefficients (P _app) for a series of model peptides, which were determined using an in situ perfused rat ileum model, were compared to the permeability coefficients (P _mono) determined using an in vitro cell culture model (Caco-2). The model peptides, which were all blocked on the N-terminal (acetyl, Ac) and the C-terminal (amide, NH2) ends, consisted of D-phenylalanine (F) residues (e.g., AcFNH₂, AcFFNH₂, AcFFFNH₂). To alter the degree of hydrogen bonding potential, the nitrogens of the amide bonds were sequentially methylated [e.g., AcFF(Me)FNH₂, AcF(Me)F(Me)FNH₂, Ac(Me)F(Me)F(Me)FNH₂, Ac-(Me)F(Me)F(Me)FNH(Me)]. These peptides were shown not to be metabolized in the in situ perfused rat ileum system. The results of the transport experiments showed that there were poor correlations between the apparent permeability coefficients (P _app) determined in an in situ perfused rat ileum model and the octanol–water partition coefficients (r = 0.60) or the hydrogen bonding numbers (r = 0.63) of these peptides. However, good correlations were observed between the in situ P _app values for these peptides and their partition coefficients in heptane–ethylene glycol (r = 0.96) and the differences in their partition coefficients between octanol–water and isooctane–water (r = 0.86). These results suggest that lipophilicity may not be the major factor in determining the intestinal permeability of these peptides and that hydrogen bonding potential may be a major contributing factor. A good correlation (r = 0.94) was also observed between the P _app values determined for these peptides in the in situ perfused ileum model and those P _mono values determined in the in vitro cell culture model (Caco-2) (Conradi et al., Pharm. Res. 8:1453–1460, 1991). These results suggest that the permeability values determined in the Caco-2 cell culture model may be a good predictor of the intestinal permeability of peptides.     

Laser Doppler flowmetry of blood perfusion in mucoperiosteal flaps covering membranes in bone augmentation and implant procedures. A pilot study in dogs.

In guided tissue regeneration (GTR) procedures, flap recession or sloughing may occur as an unwanted sequel to the placement of a membrane. This study was designed to assess the applicability of laser Doppler flowmetry (LDF) in the evaluation of blood perfusion in the mucoperiosteal flap covering the membrane. Five Labrador dogs were initially used inthe study, but one animal was later excluded due to post‐operative problems. Maxillary premolar teeth were extracted and full thickness mucoperiosteal flaps were raised. Following removal of the buccal bone plate, 4 titanium implants were placed on each side. An experimental biodegradable polylactic‐acid membrane was placed over the fixtures on one side to allow for GTR. The mucoperiosteal flap was repositioned and secured with sutures. The contralateral side served as control with no membrane. Blood perfusion was measured in the flaps before surgery, immediately after suturing and at 24, 48 and 72 h postoperatively. A laser Doppler flowmeter was used to assess the blood perfusion. In 3 animals the membrane was exposed within 2 weeks post‐operatively, and in these 3 animals the LDF values were lower on the membrane side than on the control side. The mean LDF value was lower on the membrane side for each of the 4 periods studied. The tindings suggest that LDF can be a valuable method to study blood perfusion of oral mucosal flaps and that there may be a relationship between a reduced relative LDF value and subsequent exposure of the membrane to the oral environment.     

Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C.

Cerebral perfusion was assessed with 13C MRI in a rat model after intravenous injections of the 13C-labeled compound bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-D8 in aqueous solutions hyperpolarized by dynamic nuclear polarization (DNP). Since the tracer acted as a direct signal source, several of the problems associated with techniques based on traditional dynamic susceptibility contrast (DSC) MRI contrast agents were avoided. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were calculated. The MTT was determined to be 2.8 +/- 0.8 sec. However, arterial partial-volume effects in the animal model prevented accurate absolute quantification of CBF and CBV. It was demonstrated that depolarization of the hyperpolarized 13C tracer via relaxation and the imaging sequence had little influence on CBF assessment when the time resolution of the imaging sequence was short compared to the MTT. However, CBV and MTT were increasingly underestimated as MTT or the depolarization rate increased if depolarization was not taken into account. With a modified bolus-tracking theory depolarization could be compensated for, assuming that the depolarization rate was known. Three separate compensation methods were investigated experimentally and by numerical simulations.     

温血高钾间断灌注心肌保护的临床应用

目的　探讨浅低温体外循环 (CPB)温血间断灌注心肌保护的临床效果。方法　全组随机分为对照组 (A组 )6 8例 ,采用浅低温CPB温血高钾持续灌注心肌保护。实验组 (B组 ) 91例 ,采用浅低温CPB温血高钾间断灌注心肌保护。观察两组术中心肌保护效果的差别。结果　CPB时间、主动脉阻断时间B组明显小于A组 (P <0 .0 5 ) ;库血用量和 2 4h胸腔引流量B组明显少于A组 (P <0 .0 5 ) ;主动脉开放前血钾浓度B组明显低于A组 (P <0 .0 5 ) ;主动脉开放后心脏自动复跳率B组明显高于A组 (P <0 .0 5 ) ;术后心功能临床观察两组无显著差异。结论　浅低温CPB温血高钾间断灌注保护心肌效果良好。