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Ionic and non-ionic contrast agent-mediated endothelial injury. Quantitative analysis of cell proliferation during endothelial repair.

PURPOSE: To quantitatively evaluate endothelial injury in vivo and to assess the time course of cellular repair after endothelial cell exposure to ionic and non-ionic contrast media. MATERIAL AND METHODS: Local changes at the cellular level following intraaortic injection of 1 ml of the ionic contrast agent ioxithalamate or 1 ml of the non-ionic contrast agent iomeprol, each with an iodine content of 300 mg/ml, were investigated using rat endothelium as an in vivo model. A sorbitol solution iso-osmolar to iomeprol served as control. Quantitative analysis of endothelial changes by autoradiography of 3H-thymidine-labeled endothelial cells was assessed after 3, 5 and 10 days, determining the 3H-thymidine index and the DNA synthesis rate. RESULTS: Ioxithalamate showed a clear harmful effect on the endothelium, with an elevated 3H-thymidine index of 7.68% on day 3 and 6.89% on day 5, versus 2.97% on day 3 and 2.55% on day 5 for iomeprol and 2.29% on day 3 and 1.91% on day 5 for the control. CONCLUSION: Ionic contrast agents lead to reversible transient focal endothelial cell injury. No such side effect was detectable for non-ionic contrast agents.

Animals↗

Measurement of glomerular filtration rate by fluorescent excitation of non-radioactive meglumine iothalamate.

The clearance of non-radioactive meglumine Iothalamate (Conray 60), assayed by fluorescent excitation analysis, has been shown to be a good indicator of the glomerular filtration rate (GFR). Investigations in rats by the constant infusion technique showed a good correlation with insulin clearance. In a group of ten children and one adult, we obtained excellent agreement between GFR determinations by clearance of Conray 60 and I-125 sodium Iothalamate, using the single injection technique, and taking samples from 10 min to 4 hr after injection. The decay curve was resolved into two exponential components. We have also shown that the 3 and 4 hr samples, fitted to a single exponential function, yield good agreement with GFR determinations using a double exponential model. The GFR determination method presented here is accurate, simple, cost effective, and involves no radiation exposure to the patient.

Adult↗

Differential effects of radiocontrast agents on human umbilical vein endothelial cells: cytotoxicity and modulators of thrombogenicity.

UNLABELLED: The endothelium plays a central role in the regulation of blood flow and coagulation. The impact of radiocontrast agents on endothelial cells is therefore potentially clinically important, particularly in percutaneous interventions for acute coronary thrombosis. The effects of radiocontrast agents on endothelial cell viability and determinants of thrombogenicity were studied in human umbilical vein endothelial cells (HUVECs) in vitro. Intercellular tight junctions were assessed using immunofluorescence microscopy and measurement of the transmonolayer electrical resistance (TMR). The concentrations of endothelin-1 (E), von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and thrombomodulin (T) were measured in the cell culture media. The ionic, high osmolal radiocontrast agent diatrizoate induced concentration-dependent cell death and an opening of tight junctions with the attendant abolition of the TMR. The concentration of E decreased, vWF increased in the cell culture media, the concentration of PAI-1 and T was not significantly changed by diatrizoate. Radiocontrast agents with reduced osmolality (ioxaglate: ionic; iopamidol: non-ionic) induced an increase in PAI-1 and vWF, but E and T were not significantly changed. CONCLUSIONS: Radiocontrast agents have differential effects on endothelial cells in vitro including the secretion of modulators of thrombogenesis. The effects are most pronounced in the markedly hyperosmolal compound diatrizoate suggesting a contributory role of hypertonicity. Ioxaglate and iopamidol both increased the prothrombotic factors vWF and PAI-1 to the same degree indicating a similar risk of thrombogenicity between low-osmolal ionic and non-ionic radiocontrast agents in this in vitro model.

Blood Coagulation↗

High-dose bolus urography. A superior technique in advanced renal failure.

High-dose bolus urography was evaluated in 38 patients with severe renal failure. Iothalamate meglumine (Conray 60) (2 ml/kg of body weight) was injected within one minute and nephrotomograms were taken for 30 minutes, with delayed films until 24 hours. Immediate nephrograms were obtained in all cases. The collecting systems, seen in 29 cases, were dilated in three. In the rest, obstruction could be ruled out by a combination of roentgenographic criteria. No untoward reactions occurred, and all the required information was obtained within 30 minutes. The results were superior to plain nephrotomography or infusion pyelography. We conclude that bolus nephrotomography is the procedure of choice in the investigation of severe renal failure.

Acute Kidney Injury↗

[The value and adaptability of glomerular filtration rate and reserve test (review of the literature)].

In normal conditions only 75% of kidney function capability are in use. Resting part of kidney function is called renal functional reserve. It is a very important indicator for prediction of renal insufficiency in chronic renal diseases, morphological changes or reduced mass of kidney parenchyma. More common test to estimate renal functional reserve is a method of measurement of glomerular filtration rate (clearance) before and after provocation of renal filtration by acute peroral protein load. The value and the possibilities to put in practice this test as well the factors influencing the results of glomerular filtration rate were estimated in this review.

Circadian Rhythm↗

Comparison of inulin, iothalamate, and 99mTc-DTPA for measurement of glomerular filtration rate.

Clearances of inulin, 125I-iothalamate, and 99mTc-Sn-DTPA were measured simultaneously in five mongrel dogs exhibiting a wide range of glomerular filtration rates (GFR). Standard constant-infusion inulin clearance was compared to radionuclide clearances after subcutaneous injection of the emitters mixed with aqueous epinephrine. All three substances were found to have virtually identical clearances. The accuracy, accessibility, low cost, low radiation hazard, and short half-life of 99mTc-Sn-DTPA make it an excellent substance for measuring GFR. The subcutaneous technique offers an accuracy comparable to the more difficult constant-infusion method.

Animals↗

[The effect of contrast medium injection into the left ventricle on systolic and diastolic ventricle function].

The influence of contrast medium on systolic and diastolic left ventricular function was studied in eight patients with coronary heart disease and in five dogs during and five minutes after ventriculography. Two biplane ventriculograms were performed in 5-minute intervals, in the dogs an additional one after 10 minutes. 0.66 cc/kg BW of sodium methyl-glucamin-iothalamate were injected during diastole into the left ventricel. 1. During ventriculography there are only slight changes of left ventricular volumes, pressures and diastolic compliance. The first four opacified heart cycles can be evaluated for the analysis of left ventricular function. 2. In patients with coronary heart disease there are much more pronounced alterations of systolic ventricular function 5 minutes after Ventriculography than in the normal dog. The ischemic ventricle has a reduced tolerance for volume load and negative inotropic effect of contrast media. In patients and dogs diastolic compliance is significantly increased 5 minutes after the injection of contrast medium. After 10 minutes however in the dogs compliance is significantly decreased. Analysing left ventricular function by repeated ventriculographies one has to take into account that the function is altered by the first angiogram. The degree of the changes depends on the initial hemodynamic conditions and on the time interval between the ventriculograms.

Angiocardiography↗

[Evaluation of glomerular filtration rate in clinical practice].

Glomerular filtration rate (GFR) is the most frequently used parameter to evaluate the renal function. GFR may be estimated with serum creatinine, creatinine clearance based on 24 hours urine collection or Cockcroft formula. All these methods have bias. Other approaches have thus been proposed. The limitations and advantages of isotopic methods and recent mathematical approaches (MDRD formula) are reviewed.

Chromium Radioisotopes↗

Glomerular filtration rate in children with solid tumors: normative values and a new method for estimation.

Many chemotherapy regimens used in children are nephrotoxic. Accurate dosing of these medications requires that some estimation of glomerular filtration rate (GFR) be performed prior to initiating chemotherapy. However, few studies evaluating normal GFR in children exist. The authors report normal values for GFR for children with nonhematogenous malignancies using a highly accurate method of directly measuring GFR and an equation for estimating absolute GFR in these children. Children with nonhematogenous malignancies with no evidence of renal involvement or prior use of nephrotoxic agents had their GFR measured using an iothalamate infusion methodology. A total of 111 children (males and females) with a mean age = 7.95 years (range 2.8 months-19.5 years) were included in the study. GFR adjusted for body surface area (mL/min/1.73 m(2)) increases in the first 2 years of life and then plateaus at a level comparable to adult values. GFR adjusted for body surface area for males >2 years = 131.3 +/- 22.5, females = 126.8 +/- 24.4 mL/min/1.73 m(2) (p value not significant). Absolute GFR in mL/min can be easily estimated by a simple formula (r(2) =.97) based on the child's weight and serum creatinine: GFR (mL/min) = k sqrt[ ( (agemos+ 6)* wt) / Cr serum ] where agemos is age in months, wt is weight in kg, and k = 1.05 for males and 0.95 for females. The accurate measurement of GFR remains vitally important in the safe and effective treatment of pediatric solid tumors. This study provides a set of normal GFR values for these children and an equation for easy estimate of absolute GFR.

Adolescent↗