Iron chelators do not reduce cold-induced cell injury in the isolated perfused rat kidney model.

BACKGROUND: In vitro, cold-induced injury is an important contributor to renal tubular cell damage. It is mediated by iron-dependent formation of reactive oxygen species and can be prevented by iron chelation. We studied whether iron chelators can prevent cold-induced damage in the isolated perfused rat kidney (IPK) model both after cold perfusion (CP) and after cold storage (CS). We hypothesized that in the CP model iron-dependent cold-induced injury is more pronounced, since oxygen is constantly provided. METHODS: The IPK was either flushed with University of Wisconsin (UW) solution and stored for 4, 18 or 24 h at 4 degrees C or perfused during 4 h at 4 degrees C with UW for machine perfusion. The iron chelators 2,2'-dipyridyl or desferal, or the negative control 4,4'-dipyridyl were added during the cold perfusion. Kidney function was measured during 2 h reperfusion at 37.5 degrees C and compared to a control group (without cold preservation). RESULTS: Compared to control perfusion, kidney function was decreased in all experimental protocols. glomerular filtration rate and FR(H2O) were significantly decreased, while FE(gluc) and FE(Na) were higher after 4 h CS and CP. After 4 h CP, also renal vascular resistance was increased. Addition of 2,2'-dipyridyl did not improve kidney function after either CS or CP. Prolonged periods of CS worsened kidney function. The addition of 2,2'-dipyridyl or desferal did not improve kidney function after longer periods of CS. CONCLUSIONS: Addition of an iron chelator to the preservation solution UW did not improve kidney function after both CS and CP. Iron chelation is not able to prevent cold-induced damage in the isolated perfused rat kidney.     

Image contrast using the secondary and tertiary eigenvectors in diffusion tensor imaging.

Diffusion tensor imaging (DTI) is a new imaging modality that can provide unique information on brain white matter anatomy. Measurements of water diffusion constant along multiple axes are fitted to a tensor model, from which the diffusion anisotropy and dominant fiber orientation can be estimated. Even though the tensor model is an oversimplification of the underlying neuroanatomy, information within the tensor has not been fully utilized in routine research and clinical studies. In this study we proposed and examined the properties and anatomical contents of several DTI-derived image contrasts that utilize all three eigenvectors. The new contrasts are studied and validated using known anatomical structures in ex vivo mouse brain and embryonic mouse cortex. Application to human white matter is illustrated. Our results suggest that when these contrasts are combined with a priori anatomical knowledge, they reveal neuroanatomical information that is useful for tissue segmentation and diagnosis of white matter lesions.     

How to investigate oxygen supply, uptake, and utilization simultaneously by interleaved NMR imaging and spectroscopy of the skeletal muscle.

Human skeletal muscle perfusion, oxygenation, and high-energy phosphate distribution were measured simultaneously by interleaved (1)H and (31)P NMR spectroscopy and (1)H NMR imaging in vivo. From these parameters, arterial oxygen supply (DO(2)), muscle reoxygenation rate, mitochondrial ATP production, and O(2) consumption (VO(2)) were deduced at the recovery phase of a short ischemic exercise bout. In addition, by using a reformulation of the mass conservation law, muscle maximum O(2) extraction was calculated from these parameters.     

Synthesis,separation and biodistribution of 99mTc‐CO‐MIBI complex

^99mTc‐CO‐MIBI was prepared by a two‐step procedure involving the convenient preparation of the [^99mTc(CO)₃(OH₂)₃]⁺ precursor and followed by the substitution of the water molecules by the MIBI (2‐methoxyisobutylisonitrile) ligands. In a second step, the reaction solution was adjusted to different pH values, and then the product, ^99mTc‐CO‐MIBI, was confirmed to be a mixture of two complexes: complex A and complex B, whose labeling yields could be over 90%. The ratio of complex B to the sum of A and B could increase gradually from 0 to 1 when pH was shifted from 3.0 to 9.0. These changes were monitored by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The two complexes were stable within 8 h at room temperature in vitro. The partition coefficient of the two complexes indicated that there was distinct difference between them. Biodistribution in mice demonstrated that complex B showed better myocardial imaging properties than that of complex A. The heart/liver ratios of complex A, the mixture, and complex B were 1.57, 1.93, and 2.33, respectively, for 30 min post‐injection. The discovery of chemical and biological properties of ^99mTc‐CO‐MIBI would certainly promote the research on a new promising myocardial perfusion‐imaging agent. Copyright © 2004 John Wiley & Sons, Ltd.     

贲门周围血管离断术前后肝硬化病人肝脏血流灌注的改变

目的：利用肝脏阻抗血流图探讨肝硬化门静脉高压症病人的肝脏血流灌注改变和贲门周围血管离断术对肝脏血流灌注的影响。方法：选取22例肝硬化门静脉高压症病人，分别在术前1周、术后2周检测肝血流阻抗改变，同时用Doppler检测门静脉血流动力学变化。结果：阻抗血流图表明，和对照XEG相比，门静脉高压症病人的肝动脉、门静脉向肝血流灌注明显下降，总肝灌注量降低；门静脉高压症病人术后门静脉向肝灌注增加，肝动态的向肝灌注无显著改变。Doppler测定表明门静脉高压症病人的门静脉直径增加，血流量增加，但血流速度无显著差别；术后门静脉血流动力学与术前无差别。结论：肝硬化病人肝动脉、门静脉向肝有效血流灌注都降低，肝脏总血流量下降；贲门周围血管离断术增加大部分病人的门静脉向肝血流灌注，但对肝动脉的向肝灌注无显著影响；肝脏阻抗血流图作为反映肝脏动态血流灌注的无创性检查，对于评价肝硬化病人的肝脏血流及评价手术对肝脏血流动力学的影响有一定的价值。     

Determination of an adequate perfusion pressure for continuous dual vessel hypothermic machine perfusion of the rat liver

Hypothermic machine perfusion (HMP) provides better protection against ischemic damage of the kidney compared to cold-storage. The required perfusion pressures needed for optimal HMP of the liver are, however, unknown. Rat livers were preserved in University of Wisconsin organ preservation solution enriched with acridine orange (AO) to stain viable cells and propidium iodide (PI) to detect dead cells. Perfusion pressures of 12.5%, 25% or 50% of physiologic perfusion pressures were compared. Intravital fluorescence microscopy was used to assess liver perfusion by measuring the percentage of AO staining. After 1-h, the perfusion pressure of 12.5% revealed 72% +/- 3% perfusion of mainly the acinary zones one and two. The perfusion pressure of 25% and 50% showed complete perfusion. Furthermore, 12.5% showed 14.7 +/- 3.6, 25% showed 3.7 +/- 0.9, and 50% showed 11.2 +/- 1.4 PI positive cells. One hour was followed by another series of experiments comprising 24-h preservation. In comparison with 24-h cold-storage, HMP at 25% showed less PI positive cells and HMP at 50% showed more PI positive cells. In summary, perfusion at 25% showed complete perfusion, demonstrated by AO staining, with minimal cellular injury, shown with PI. This study indicates that fine-tuning of the perfusion pressure is crucial to balance (in)complete perfusion and endothelial injury.     

Normothermic ex vivo lung perfusion of non-heart-beating donor lungs in pigs: from pretransplant function analysis towards a 6-h machine preservation

Donor shortage urges optimal use of all lungs available. Ex vivo lung perfusion (EVLP) is a method to evaluate lung function before implantation. EVLP was performed in pigs to evaluate lung function, using two different clinical non-heart-beating (NHS) donor protocols: flush perfusion and topical cooling after 1-h warm ischaemia (n = 5 each). Secondly, we investigated whether EVLP can be used for 6 h ex vivo machine preservation (n = 4). In comparison with topical cooling, flush perfusion preserved lung function better during EVLP. During 6 h normothermic EVLP, gas exchange remained stable; however, the pulmonary artery pressure and ventilation pressure showed a significant increase. EVLP is a reliable method for evaluation of lung graft function. Flush perfusion with Perfadex is preferred above topical cooling in NHB lung donation. Six-hour normothermic EVLP is feasible but should be further improved to make ex vivo machine preservation or treatment of lung grafts successful.     

逆行灌注心脏不停跳心脏手术犬血浆降钙素基因相关肽的变化

目的 :探讨经冠状静脉窦逆行灌注心脏不停跳手术对犬降钙素基因相关肽的影响。方法 :将 1 6只健康杂种犬随机分为浅低温逆行灌注心不停跳组 (实验组 )与中度低温心停跳组 (对照组 ) ,每组 8只。体外循环 (CPB) 1 5 0 m in。于 6个时点采集静脉血 ,检测血浆降钙素基因相关肽 (CGRP)。结果 :两组 CPB期间 CGRP与 CPB前比较均有不同程度升高 ,实验组 CGRP较对照组升高快 ,在 CPB结束达峰值 ,实验组与对照组 CGRP在 CPB中各时点比较差异均有统计学意义 (P <0 .0 1或 P <0 .0 5 )。结论 :CGRP可作为 CPB过程中检测心肌保护效果的敏感指标 ;心脏不停跳手术法有利于 CGRP的合成和释放 ,具有较佳的心肌保护作用     

In vivo imaging of extraction fraction of low molecular weight mr contrast agents and perfusion rate in rodent tumors

Tissue uptake of a fully extractable MR detectable tracer, deuterated water (D₂O), was compared with that of a less extractable contrast agent, Gadolinium-DTPA-dimeglumine (Gd-DTPA), in rodent tumor and muscle tissue. This dual tracer method allowed calculation of relative (to muscle) tissue perfusion and extraction fraction of Gd-DTPA in each image pixel in vivo. Solutions of Gd-DTPA and D₂O were injected intravenously into Fisher female rats (n = 9) with R3230 mammary adenocarcinomas implanted in the hind limb. Perfusion rate was approximately two times greater (P < 0.005 by paired t test) in tumor than in muscle. Gd-DTPA extraction fraction at the interface between tumor and muscle was 2.0 times the extraction fraction in normal muscle (P <0.005 by paired t test). Extraction fraction at the tumor center was 1.6 times the extraction fraction in muscle (P <0.01 by paired t test). High extraction fraction of Gd-DTPA correlated with high capillary permeability determined from Evans Blue staining. Low molecular weight Gd-DTPA derivatives are widely used in clinical practice, and their extraction fractions are crucial determinants of image contrast during the first few passes of the contrast agent bolus. Therefore spatially resolved measurements of contrast agent extraction fractions obtained in vivo have significant clinical utility. The data demonstrate that extraction of low molecular weight tracers is sensitive to increased permeability in tumor vasculature and that this increased permeability can be imaged.     

豚鼠肾灌注模型及其吸收大鼠天然抗体的实验研究

本实验建立了豚鼠肾灌注模型，观察了３２例豚鼠肾灌注后ＳＤ大鼠天然抗体的动态变化。结果３２例豚鼠肾灌注手术均获成功，ＳＤ大鼠体天然抗体于灌注后１５分钟内有显著下降（Ｐ〈０．０１），抗全效价从１：３２－１：６４下降至１：４－１：８；１５－３０分钟内又有所下降（Ｐ〈０．０１），从１：４－１：８下降至１：２－１：４；３０－６０分钟后下降不明显（Ｐ〉０．０５）。病理检查显示豚鼠灌注肾血管充血、出血及明显的血