Acetylation of human serum albumin by acetylsalicylic acid.

Human serum albumin is acetylated when exposed to acetylsalicylic acid (aspirin) under physiologic conditions in vitro. Indications are that a similar phenomenon occurs in vivo after ingestion of aspirin.

Failure to induce hypersensitivity reactions to opaque contrast media analogs in guinea pigs.

In a further exploration of idiosyncratic reactions to injections of contrast media, a systematic study of immediate or delayed hypersensitivity in guinea pigs injected with contrast media analogs was performed. No evidence of immediate or delayed hypersensitivity could be ascertained to either contrast media analogs alone, or analogs bound to protein carriers. This does not represent conclusive evidence against the notion of antibody formation as a factor in the production of some adverse reactions, but makes such a pathogenesis less likely.

Mechanism of renal excretion of various X-ray contrast materials in rabbits.

The excretory behavior of nine nephrotropic contrast agents with varying physicochemical properties such as charge, lipophilicity, and molecular size was investigated. Renal clearance in comparison with inulin was determined by means of the continuous infusion method. Each contrast agent was infused at three dose levels in four to six rabbits. The investigations show that tubular transportation in proportion to glomerular filtration decreases with increasing dosages of all the contrast agents. Thus, with the highest concentration in plasma all contrast agents are eliminated at more or less the glomerular filtration rate (GFR). After administration of the low dosages the following differences are found: 1) Net tubular secretion increases for the monomeric contrast agent acids with increasing lipophilicity, in the order diatrizoate congruent to iothalamate less than iodamide less than acetrizoate. 2) The clearance studies do not reveal any tubular secretion or reabsorption for a hydrophilic cationic contrast agent. 3) The nonionic contrast agents do not show net secretion. The more lipophilic they are, the more they are reabsorbed. 4) Two dimeric contrast agents also do not reveal any tubular secretion. They seem to be reabsorbed more than monomers with the same charge.

The allergic theory of radiocontrast agent toxicity: demonstration of antibody activity in sera of patients suffering major radiocontrast agent reactions.

An allergic, immunologic mechanism for certain adverse reactions to radiocontrast agents has been postulated on the basis of clinical and theoretical considerations. One obstacle to the acceptance of this allergic theory has been the inability to demonstrate significant antibodies with specificity for these agents. In our studies, rabbits were immunized with 4 analogues of radiocontrast agents which induced IgG or IgE antibodies specific for the contrast media analogues. Then, to determine if antibodies to contrast agents were present in man a prospective, one-year surveillance of radiocontrast agent reactions was undertaken. Sera from 27 patients suffering severe reactions and 37 control subjects were analyzed by radioimmunoassay for antibodies reactive with radiocontrast media. Binding of radiolabeled contrast media was significantly elevated (p less than 0.01) by the serum globulin fraction of the patients suffering severe reactions. Demonstration of this antibody activity, although not proof of cause and effect between the presence of antibody activity and clinical symptoms, nonetheless adds support to the hypothesis that some adverse reactions to radiocontrast agents are due to antibodies.

Activation of serum complement by contrast media.

Evidence is presented for the activation of serum complement by contrast media, in vitro and in vivo. Activation as a function of concentration was measured and the increasing order of effectiveness was found to be metrizamide, iothalamate, diatrizoate, acetrizoate, iodipamide and iopanoate. This order is the same as for protein binding and enzyme inhibition. The activation mechanism for iodipamide, and by inference for the other compounds, does not involve gamma-globulin aggregation. Serial daily injections in normal dogs resulted in substantial declines in serum complement over several days. Guinea pigs which were depleted of serum complement with cobra venom factor were found to be no less sensitive to lethal doses of iodipamide than those with normal complement. Implications of these findings are discussed.

[Renal toxicity of contrast media. Experimental study on dogs (author's transl)]. / Beitrag zur nierenschädigenden Wirkung der Kontrastmittel. Experimentelle Arbeit an Hunden

Experiments injecting Indian ink have confirmed the theory that postangiographic renal damage is due primarily to ischaemia. Cortical ischaemia is due to vascular spasm and sludging caused by contrast medium. Current and previous experimental findings suggest the following course in the pathomechanism: vasospasm reduced blood velocity--aggregation of erythrocytes--further deterioration in the circulation--microemboli--irreversible sludge formation--arterial and venous thromboses--ischaemic foci--necrosis or infarction. It is not possible to prevent this damage by alpha blocking sympathicolytic drugs.