Search

The paper considers the mechanisms of development of contrast-induced nephropathy in the use of iodinated radiopaque contrast agents (RCAs), as well as the criteria of their assessment. It gives different existing recommendations for prevention of the nephrotoxic effects of RCAs.

The paper discusses the concept of risk-group patients who have an increased probability of immediate systemic adverse reactions to contrast agents used clinically in various radiodiagnostic techniques. It analyzes the pathogenesis of allergoid reactions to X-ray and magnetic resonance, contrast media. On this basis, the authors describe the abnormalities and nosological entities the patients had in their medical history before diagnostic studies will be indicative of the increased risk of these complications to the administration of a contrast agent.

It is shows that the diagnostic Roentgen contrast media (RCM) in a dose of 2.0 g iodine/kg increase the activity of lactate dehydrogenase in rat blood, the effect decreasing in the following order: iodamidebilignosttriombrastperitrastmelitrastomnipaquehexabrix. At the same time, the RCM in a dose of 0.5 g iodine/kg (iodine concentration, 0.03-30 mg/ml) and gadolinium-containing magnetic-resonance contrast media (MRCM) in a dose of 0.1 mM/kg (gadolinium concentration, 0.2-1 mg/ml) inhibit the enzyme, the effect decreasing in the following order: bilignost = iodamide = triombrast = peritrasthexabrixomnipaque = melitrast = ultravist = magnevist = dipentast. The mechanism of action of the contrast media on the LDH activity was studied and it was found that changes in the enzyme activity is correlated with the toxicity (LD 50) of RCM. The groups of risk from the standpoint of side reactions to the intravenous RCM introduction are determined.

The study conducted proved that triombrast (dose dependently)hexabricsUltravistor = melitrast = omnipac in a concentration interval of 0.03-30.0 mg iodine/ml in vitro and in a dose interval of 0.5-2.0 g iodine/kg in vivo activate the complement system (CS) according to the alternative way in the blood of "sensitive" rats. The degree of CS activation by radiopaque agents (ROA) is significantly determined mathematically by their viscosity and relation of the number of iodine atoms to the number of ions or dissolved particles, and by their hydrophilic (for nonion CS) and osmotic (for ion monomeric CS) properties.

epsilon-Aminocaproic acid and prednisolone in concentration of 3.0 x 10(-5) M are proven to reduce or even completely prevent activation of the alternative pathway of the component which has been induced by iod-amide adipiodone and triombrast in concentrations 2.5 x 10(-2) M in the serum of "sensitive" rats. The preventive effect of the glucocorticoid appeared less pronounced. There exists direct positive correlation between the degree of the component activation with radiopaque compounds and preventive effect of the drugs studied.

It was demonstrated in rat experiments that a positive direct correlation exists between the decrease in the amount of histamine in rat peritoneal must cells after intravenous infusion of radiopaque agents (ROA) in a dose of 2 ml/kg and the amount of these penetrating from the blood into the peritoneal cavity. The degree of penetration is determined by the chemical structure and/or physiochemical properties of the ROA.

During 73 single contrast investigations with 76% triobrast, 76% verographin, 76% urographin, urotrast and omnipaque-300, 65% of patients had clinical adverse reactions which were mainly mild. In 79% of cases, the syndrome of side effects consisted of one clinical manifestation. The occurrence of clinical adverse reactions caused by diatrizoate derivatives was proved to be associated with the elevation of blood levels of histamine and prostaglandin F2 alpha, with the activation of the complement system by an alternative pathway and to be independent of the sex and age of patients. According to the effects of contrast media on these blood biochemical parameters, patients are classified as "tolerant" and "sensitive", the proportion of the latter is 50-80%. With this, plasma histamine levels greater than values of the capacity of the complement system to activate by the alternative pathway greater than blood prostaglandin F2 alpha amounts may serve as mathematically significant criteria for the likelihood of side reactions occurring in the contrast diagnosis with diatriazoates. An elevated diastolic pressure is a valid symptom of side effects of the radioopaque media tested by us on the human body.

The effects of radiopaque agents on peripheral blood T-lymphocyte blast transformation were in vitro studied in healthy donors. It was shown that depending on the dose and type, radiopaque agents activated spontaneous proliferation of these cells and inhibited or activated PGA-induced proliferation. An individual sensitivity of peripheral blood lymphocytes to the radiopaque agents was revealed. There was a positive correlation between the functional response of peripheral blood lymphocytes to PGA and the degree of bilignost-induced inhibition of this reaction. There was also antagonism of some radiopaques in response to peripheral blood T-lymphocyte blast transformation.

The in vivo and in vitro effects of radioopaque agents such as bilignost, iodamide, and triombrast on blood thromboxane B2 (TxB2) and prostacyclin levels were studied in man and rats. These radioopaque agents were demonstrated to increase prostacyclin levels and to decrease TxB2 in the plasma by 40%, as evidenced by urography when given in vivo (1-2 g/kg) and in vitro (2.5.10(-2) M and 2.5.10(-3) M).

The data on immunodepressants most commonly used in the Soviet Union in the diseases caused by disorders in normal function of the immune system are presented. Such drugs as cyclosporine A, cyclophosphan, azatioprine, 6-mercaptopurine are considered. Emphasis is given to the mechanism of the primary pharmacological response of the drugs to the immunocompetent cells, the grounding of their clinical use, dosage and mechanisms of possible side effects.

Bilignost, iodamide and triombrast were shown to increase the concentration and to decrease the size of the rat blood serum immune complexes in vivo and in vitro. A decrease of the size of immune complexes was also observed during angiography with the use of triombrast in humans. According to the relation to the action of roentgen contrast media on the concentration and size of immune complexes humans and rats can be divided in "sensitive" and "tolerant" ones.

The effect of roentgen contrast media (RCM)--50% bilignost, 76% triombrast, 80% iodamide-380, on degranulation of peritoneal mast cells in rats was studied. It was found that 20 minutes after intravenous injections of RCM the content of intracellular histamine significantly decreased. This effect depended on the drug dose and increased in the order: triombrast, iodamide, triiotrast, bilignost. Different sensitivity of animals to the histamine-releasing effect of RCM was detected by using the nonparametric method of mathematical statistics. The number of "sensitive" animals was 50-75%.

The purpose of the work was to demonstrate the effect of radiographic contrast media (RCM) 50% bilignost, 76% triombrast, 80% iodamide-380 on the complement system in rats. It has been found that RCM cause alternative complement activation during incubation with the whole blood or serum in vivo and in vitro. The RCM effect value depends on the drug dose and increase in the order: triombrast iodamide bilignost. Different sensitivity of animals to the effect of RCM on the complement system has been shown.