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Assessment Of L-NAME Induced Hypertensive Renal Injury By SPECT And MSCT In Rabbit Experimental Models

Posted on:2012-07-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:W H WangFull Text:PDF
GTID:1484303356992259Subject:Medical imaging and nuclear medicine
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Object:?Utilizing SPECT examination techniques and using different doses of L-NAME(N-nitro-L-arginine methyl ester) induced hypertensive renal injury in the model can obtain the determination of renal function, the changes of Lateral renal function, the analysis of Lateral renal function and kidney uptake function, and urinary excretion of smooth. Dynamic observation and semi-quantitative assessment of pre-clinical and clinical drug dependence can provide imaging evidences during the longitudinal extent of renal injury in experimental basis in-depth study.?The assessment of MSCT examination technique can be used by the dynamic effects of different doses of L-NAME in rabbits. Re-using CT perfusion parameters and glomerular filtration rate (GFR) can be determined on the quantitative assessment of the extent of renal injury. The comparison between the GFRCT and GFRSPECT also can obtain a result whether there was a correlation between the degrees, so that to explore the value of MSCT examination technique about the one renal function. Materials and methods:Part?:Experiments were carried out New Zealand white rabbits (body weight 2.5?3kg, n=31) which divided into three groups. One group served as the control and received NaCl 0.9%(Vehicle, n=9) while each of the remaining groups received one of two doses of L-NAME:3mg/kg (n=12), and lOmg/kg (n=10). During the experiments (infusion and imaging), a 2 ml/kg bolus of the relative treatment solution was administered via the rabbit ear vein i.v.catheter (t=0), followed by a constant infusion (i.v.0.17 mlmin/kg) over a period of 30 min at the specified dose. The detected channel creatinine and hematocrit were measured before and after the injection by ear vein blood.It was to obtain the parameters by SPECT examination, including Cr, SBP, GFR, TTP and T1/2.The selection of another 15 rabbits was necessary because the blood pressure measurement was invasive. The experimental rabbits were divided into 3 groups according to the aforementioned injection method: normal control group (n-5), L-NAME3 group (n-5) and L-NAME10 group (n-5). The left femoral artery was exposed by surgery. After the separation of intubation, the connection pressure gauge measured systolic blood pressure into anesthetic rabbits (SBP). Part?: Experiments were carried out mentioned above which divided to three groups:normal control group (n=6), L-NAME3 group (n=6) andL-NAME10 group (n=8). Three groups were carried by MSCT within 5 minutes, and then by SPECT with 24 hours(n=15). It was to obtain the CT perfusion images and the perfusion parameters, including BF, BV, MTT, and PS. Observing the kidney cortex and medulla of the different degree of enhancement. Finally, the raw data can be transferred into the post-processing workstation to get the image processing and GFR calculation. It was same to the first part of SPECT examination. Statistical analysis used the SPSS for windows 13.0 statistical software package. The comparison between groups was analyzed by one-way ANOVA and Bonferroni. Results:Part I: L-NAME induced hypertensive renal injury in the model of rabbits successfully established because of the results about the increasing dependence and declining GFR. L-NAME3 group GFR comparing with the control group GFR decreased slightly. As 35 ml/min impaired renal standard, the diagnostic sensitivity and specificity was 100%. (?)he two groups comparison Had statistical signification. Compared with the control group, this TTP also extended for about 2 min. The two groups'comparison had statistical signification. The TTP of the high-dose L-NAME10 group had no statistical signification with low dose L-NAME3 group's TTP. Comparing with the control group, T1/2 had a significantly extension. Part II:Comparing the L-NAME3 group, L-NAME10 group and the control group, the difference of the BF, BV, PS perfusion values between the first two groups and the last group had the statistical signification. Especially the difference of BF and BV of renal cortex between the L-NAME3 group and L-NAME10 group also had the statistical signification. The difference of BF and BV of renal outer medulla and inner medullary renal parenchyma between the L-NAME3 group and L-NAME10 group had the statistical signification. The renal cortex, outer medulla, inner medullary peak enhancement and all the differences of the peak enhaneement between the first two groups and the last group had statistical signification (p< 0.05). The difference of the peak enhaneement between the L-NAME3 and the L-NAME10 group also had statistical signification. The peak time of renal cortex, outer medulla, and real area in the L-NAME3 and the L-NAME10 group was significantly longer than the peak time in the control group, and the differences of the peak time between the first two groups and the last group had statistical signification (P<0.05). The difference between the L-NAME3 and the L-NAME10 group also had statistical signification because the L-NAME10 group's GFRCT was deeply lower than the L-NAME3 group's (P=0.000). The differences had statistical signification when the LNAME10 group's GFRSPECTt compared with the control group's GFRSPECTt (P=0.000). If GFRSPECTt was the standard, enhanced CT and SPECT examination of the two measurement methods were carried out by the GFRCT and GFRSPECTt Spearman rank correlation and rank regression analysis. The correlation coefficient between the groups was 0.913?0.954 (p<0.05), two measurement methods were obtained GFRCT and GFRSPECTt highly relevant. Meanwhile, the determination coefficient is from 0.833 to 0.911 (p<0.05). The kidney damage of the L-NAME10 group was more terrible than the other two previous groups. The renal pelvis and calyx structure was incomplete. There also was kidney renal ischemia, congestion, and other diseases. From the light microscope, the renal tubular epithelial cells swelled, the tatty degenerated and the vacuolar degenerated. It can be easy to observe a large number of renal tubular epithelial cells in the formation and renal tubular necrosis of renal interstitial edema. Conclusion:?As a selective inhibitor, NOS can cause the increasing of dose-dependent blood pressure. In a short period of time, using SPECT can observe the changes of renal hemodynamic.?At the same time, using SPECT can analysis the kidney, especially the intake of a single kidney, excretory function and urinary tract smooth conduct. This method can be used as a new dynamic clinical treatment evaluation of experimental basis. This method also can help the clinical observation and evaluation of renal injury in the case of drug dependence on preclinical and clinical studies of experimental drugs.?Measured using MSCT can check the parameters of the kidney. Especially the GFRCT can directly and quantitatively reflect the changes in renal function, and the results by SPECT have a higher consistency.?MSCT not only is highly reproducible, objective, intuitive, but also provides important imaging evidence for clinical observation and evaluation of dynamic renal injury on the clinical early detection.
Keywords/Search Tags:Hypertensive, renal injury, SPECT, MSCT, L-NAME, glomerular filtration rate, consistency, animal experiments
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