Sandra G. Lyon

Steroids: theoretical and experimental basis for utilization in prevention of contrast media reactions.

In vitro and in vivo studies were done to examine the effects of methylprednisolone on the adverse reactions induced by contrast media. At very high concentrations, the steroid potentiated the complement-activating effect produced in vitro by iodipamide, but inhibited the immune and nonimmune mechanisms of hemolysis. Rabbits pretreated for 3 days with intramuscular methylprednisolone (at high or low dosages) were significantly protected against an LD47 challenging dose of iodipamide. Those treated once with a low intravenous dose immediately prior to iodipamide challenge were protected to a lesser degree. Rabbits treated once with a very high intravenous dose of steroid evidenced no protection. A hyper-responsive dog was consistently protected against adverse reactions to injected sodium iothalamate by a 3-day steroid pretreatment.

Complement and contrast material reactors

Patients showing systemic reactions to intravascular contrast media and patients receiving contrast media without reaction have significantly different mean values (p is less than 0.05) for functionally determined serum C1-esterase inhibitor (C1 INH) and total hemolytic complement (CH50). The lower concentration of these components in reactors appears in baseline serum samples (as well as after injection), and suggests that many anaphylactoid reactions to contrast media are conditioned by earlier complement consumption, and result directly from contrast-induced activation of complement, and other activation system components in the presence of inhibitor depression.

Heparin-like anticoagulants in asthma

In a previous study, and in the present study, we have found that the baseline plasma samples of patients with asthma contain average levels of an endogenous heparin‐like material (EHM) that is significantly higher than that noted in non‐allergic, non‐asthmatic controls. This material appears to have properties of both heparin and heparan sulfate. Three out of six patients responding to inhalational antigen challenge displayed an acute increment in EHM concentration that coincided with a fall in FEV1 values. The relation of EHM concentration to provoked asthma, or to asthma in general, remains to be determined.

Activation systems in contrast idiosyncrasy.

Both animal and human data suggest the possibility that the C1 esterase inhibitor may play an important controlling role in contrast media systemic reactions. This critical controlling protein has a major inhibitory effect on C1, kallikrein, activated factor XII of the intrinsic coagulation system, and on plasmin. In addition, it probably has other inhibitory effects not so well documented. Any circumstance that contributes to a continuing activation of the complement, coagulation, kinin, or fibrinolytic systems may result in partial consumption of the inhibitor and predispose the individual to adverse reactions to contrast challenge.

Changes in complement and coagulation factors in a patient suffering a severe anaphylactoid reaction to injected contrast material: some considerations of pathogenesis.

A patient, suffering a severe anaphylactoid reaction to contrast material injected for an intravenous pyelogram, developed a consumption coagulopathy and evidence of complement activation. Precontrast complement values suggested that the patient had been processing complement via the classical pathway, perhaps as a consequence of an earlier protracted Klebsiella infection. Following contrast injection, a precipitous fall in total hemolytic complement (CH50) and in the concentration of the C1 esterase inhibitor (C1 INH) developed, as well as a diminution in C4 and C3 with the evolution of C3 conversion products. The possible role that these changes might play in the pathogenesis of idiosyncratic reactions to contrast media is considered.

The plasma contact system in atopic asthma

An in vitro test for the rate of appearance of kallikrein in plasma due to contact system activation by dextran sulfate at 0 degree C was applied to plasmas of 19 atopic asthma patients and 19 age- and sex-matched controls without atopy. The average prekallikrein activation rate was markedly higher in the plasmas of the atopic patients. Mean endogenous heparin levels were also elevated.

A role for nitric oxide in x-ray contrast material toxicity

RATIONALE AND OBJECTIVES We assessed the role that nitric oxide (NO) plays in contrast media (CM) toxicity, using 100% lethal dose (LD100) studies in hyperimmune Brown Norway (BN) rats. METHODS Ninety-two BN rats and 41 Sprague-Dawley (SD) rats underwent CM LD100 tail vein injections with methylglucamine iothalamate or sodium iothalamate to the point of cessation of respiration. Methylglucamine hydrochloride also was injected. The injections were accompanied by L-arginine (L-Arg) or D-arginine (D-Arg) analogues or by an H1 blocker. L-Arg analogues inhibit NO formation, and D-Arg analogues do not. RESULTS An L-Arg analogue, but not a D-Arg analogue, increased the tolerance of BN rats (p < .005) for methylglucamine iothalamate but not for sodium iothalamate. The L-Arg analogue also protected BN rats against methylglucamine chloride injections (p < .002). H1 blockade protected BN rats against methylglucamine iothalamate (p < .0005) and methylglucamine chloride (p < .005) injections. None of these measures altered the CM tolerance of SD rats. In SD rats, injections of either methylglucamine iothalamate or sodium iothalamate along with a D-Arg analogue or normal saline were better tolerated than similar injections in BN rats (p < .01 and .002 for methylglucamine iothalamate and sodium iothalamate, respectively). In SD rats but not BN rats, sodium iothalamate was better tolerated than was methylglucamine iothalamate (p < .0005). CONCLUSION NO appears to play a significant role in BN rats LD100 CM toxicity and has been implicated by others in the blood pressure fall characterizing some forms of antigen-induced anaphylaxis [1, 2]. The results of the current study and the literature suggest that methylglucamine-modulated release of histamine from mast cells may underlie the NO production.

Inhibition of angiotensin-converting enzyme by contrast media. I. In vitro findings.

There is increasing evidence that activation of the plasma contact system that results in the production of bradykinin plays an important role in contrast material systemic reactions. The effects of bradykinin in anaphylaxis depend on its rate of destruction and its rate of production. The highest percentage of contrast material reactions occur after intravenous injections, and the major enzyme hydrolyzing bradykinin (kininase II; angiotensin-converting enzyme) is found on pulmonary vascular endothelial surfaces. The inhibitory effects of numerous ionic and nonionic contrast material solutions on the enzyme have been determined. Additionally, the role in this inhibition of the chelators found in all commercial contrast material vials has been studied. In vitro, all such preparations combined with their chelators inhibit angiotensin-converting enzyme. Whether this inhibition plays a role in vivo remains to be established.

Effect of endotoxemia on contrast media reactions.

Since complement activation is sharply temperature-dependent, we have examined the effects of fever produced by a very small dose of endotoxin on contrast media lethality in rabbits. After the injection of 8.2 ml/kg of 52% methylglucamine iodipamide, a group of rabbits exhibiting an average temperature elevation of 1.5 degrees C had a 100% mortality rate. This was contrasted to a 30% mortality in control rabbits receiving contrast alone, and no mortality in rabbits receiving endotoxin alone. The rabbits with fever and increased mortality exhibited increased activation of serum complement. From this preliminary data it appears that caution should be observed in performing a contrast examination in a patient with endotoxemia and/or a fever.

Analogous features of cold-promoted activation and contact system activation in human plasmas: the role of cryptic soluble surfaces in asthma oral contraception and pregnancy.

Aspects of cold-promoted activation (CPA) and contact system activation (CSA) of human plasma were assayed in 13 normal subjects, 11 asthmatics and 15 patients with history of allergy to x-ray contrast media, to see whether the phenomena were correlated. Cold activation commonly occurs in stored plasma in 60% of women taking oral contraceptives, 93% of women in 3rd trimester of pregnancy, but only 15% of normal subjects. It is assayed by measuring kallikrein. CSA also occurs at low temperatures, but is dependent on soluble negatively-charged surfaces. It is assayed using dextran SO4 or polybrene. In this study, kallikrein amidolytic activity with dextran SO4-CDA and cold-dilution CDA were positively correlated in asthmatics. The allergic patients showing elevated B-CDA values also had shortened Thrombotest times with cold dilution, while those with normal B-CDA values had normal coagulation times. The significance of these results were discussed, including the theoretical possibility that cryptic surface phenomena may be involved in the heightened coagulability of plasma in women taking oral contraceptives.