Zaheer Parvez

Contrast media-induced lipid peroxidation in the rat kidney.

Lipid peroxidation of biological membranes is often implicated in tissue injury. The authors compared the effects of ionic and nonionic contrast media (CM) on the induction of lipid peroxidation in rat kidney and its impact on renal function. Male Wistar rats weighing 200 to 230 grams were dehydrated for 24 hours and divided into 6 groups (n = 15/group). On day 0, groups 1 through 3 were injected with 25% glycerol (10 mL/kg, im) and rats from groups 4 through 6 received an equivalent amount of intramuscular saline. The next day, rats from groups 1 and 4 were injected with normal saline (10 mL/kg, iv); groups 2 and 5 received the ionic CM, diatrizoate, and groups 3 and 6 received the nonionic CM, iopromide. Each CM was tested at 10 mL/kg BW. At 24-hour intervals, 5 rats from each group were sacrificed. In rats injected with CM (diatrizoate or iopromide) alone, no changes in serum creatinine or kidney structure were demonstrated. In glycerol treated rats, a peak in serum creatinine was seen on day 2 which returned to normal level by day 4. Histologic changes included focal tubular damage and intraluminal debris. Malondialdehyde (MDA), a marker of lipid peroxidation concentration was higher than in controls (P less than 0.05). In diatrizoate-injected rats, increase in serum creatinine on day 4 was ten times higher than glycerol; severe morphological alterations in proximal tubules were noted and significant increases in renal MDA concentration were obtained (P less than .05). Iopromide (on day 4), caused a five-fold increase in serum creatinine compared with glycerol.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Nonionic Contrast Media (CM) on the Components of Coagulation and Complement Systems

Several nonionic experimental contrast media (CM) were evaluated for their effects on coagulation cascade, platelet aggregation, and the activation of complement pathways. In an in vitro system, most of the contrast media tested showed a mild anticoagulant property by prolonging the clotting times, such as partial thromboplastin time and the thrombin time of pooled normal human plasma. However, aggregation of normal human platelets by adenosine-diphosphate (ADP), collagen, epinephrine, ristocetin, and thrombin was not blocked when the platelet-rich plasma was incubated with these agents. No quantitative or qualitative changes in the complement components C3 or C4 were detected when a mixture of CM and pooled normal human serum was analyzed by radial immunodiffusion, immuno- or crossed-immunoelectrophoresis techniques. These results indicate that nonionic contrast media produce certain transient hematologic changes and should be further tested for their immunologic properties in order to establish their absolute safety in diagnostic procedures.

Antiplatelet action of intravascular contrast media. Implications in diagnostic procedures.

The antiplatelet action of intravascular contrast media (CM) Renografin-76 (diatrizoate meglumine and diatrizoate sodium) was studied in vitro and in 21 patients undergoing radiodiagnostic procedures. In vitro studies suggested that in Renografin-76, meglumine was the chief constituent responsible for its antiplatelet action. In post-CM plasma from patients, clotting times were prolonged and platelet aggregation greatly impaired, albeit normal aggregation restored within 3 hours. Although changes in global clotting times and platelet aggregation were mostly transient, it is possible that CM usage in patients with thrombocytopenia, sickle cell phenomenon, and on anticoagulant-antiplatelet drugs may present a serious risk to their hemostatic integrity.

Nonionic Contrast Medium: Effects on Blood Coagulation and Complement Activation In Vitro

A nonionic contrast medium was evaluated in vitro for its effects on coagula tion and complement activation in comparison to a low osmolal contrast agent. In clotting assays each contrast medium was mixed with blood and clotting parameters were analyzed by using a thromboelastographic machine. Platelet function was studied by incubating platelet-rich plasma with individual contrast medium, and the subsequent challenge of a platelet aggregating agent. Comple ment activation was assessed by the hydrolysis of C3 protein into C3c fragment in contrast medium-incubated serum. Immunoelectrophoresis was used to detect C3c protein. Both the nonionic contrast medium and the low osmolal contrast agent acted as anticoagulant and antiplatelet agents, however, results with the low osmolal contrast agent were more pronounced compared to the nonionic contrast medium. Even at nonphysiologic concentration of contrast medium, no significant conversion at C3 to C3c was seen. Since these two agents caused hypo coagulable states in vitro, it is likely that patients with thrombocytopenia, se vere liver disease and with clotting factor deficiencies may present hemostatic complications during angiographic procedures.

Effect of contrast media on prostaglandin synthesis in vivo.

Parvez Z, Marsan RE, Moncada R, Patel N. Effect of contrast media on prostaglandin synthesis in vivo. Invest Radiol 1988; 23(Suppl 1):S178‐S181. Since systemic reactions to contrast media (CM) in patients often resemble pathophysiologic conditions associated with prostaglandin metabolites prostacyclin (PGI2), and thromboxane B2 (TXB2), plasma levels of these mediators are likely to provide an index of CM pathogenesis. In this study, patients undergoing peripheral arteriography were injected either with a hyperosmolal CM sodium diatrizoate or with a newer low osmolal CM, iohexol. Arterial blood samples were collected before and after the procedure. Prostacyclin and thromboxane were quantified as 6 ketoprostaglandin F1a (PGF1a) and TXB2 by using radioimmunoassay kits. Diatrizoate caused prostaglandin I2 (PGI2) release in 60% of patients, whereas 66% receiving iohexol also exhibited increased levels of PGI2 in their plasma. TXB2 concentration remained unchanged. No clinically adverse reactions were seen following the procedure. These results indicate that both high and low osmolality CM are capable of stimulating vascular endothelium, thereby causing prostacyclin release. Molecular mechanisms, however, remain to be determined.

Ultrastructural changes in rat aortic endothelium during contrast media infusion.

A rat model was employed to investigate contrast media (CM) induced ultrastructural changes in the vascular endothelium. Ionic contrast materials such as Renografin-76 (diatrizoate meglumine diatrizoate sodium), MD-76 (diatrizoate meglumine diatrizoate sodium), and Angiovist (meglumine diatrizoate) were injected into the femoral vein of anesthetized male Wistar rats (240-260 g) and allowed to circulate. Control animals were similarly injected with equiosmolar sucrose and physiologic saline. The thorax was opened 15 minutes, 1 hour, and 4 hours postinjection and cardiac perfusion performed using Karnovskys fixative; the thoracic aorta was then surgically removed, and processed for transmission electron microscopy. All CM produced shrinkage in cell cytoplasm and nuclear structures thereby causing distortions in cell morphology. In control tissues, however, no such ultrastructural damages were noted. Within 15 minutes of CM infusion, electron dense granules were seen on the luminal surface of endothelial cells, in pinocytotic vesicles, as well as in the gap junctions between cells. These observations indicate that contrast media intake occurs via vesicular transport, and through the cell junction.

Laser nephelometric quantitation of antithrombin-III (AT-III) development of a new assay

Abstract Antithrombin-III (AT-III) concentration in normal healthy volunteers and in an out-patient population was determined by a radial immunodiffusion (RID) and by a laser nephelometric technique, developed in our laboratory. In 43 normal individuals tested, the mean AT-III concentration by laser nephelometry was 24.1 ± 3.3 mg/dL or 108 ± 13% normal human plasma pool (NHP). The coefficient of variation (CV) of the assay was in the order of 7–10% and there was a good correlation (r=0.81) between RID and laser nephelometric method. Some developmental aspects of the laser nephelometric procedure and its advantages over the RID method are discussed.

Contrast media-induced chromosomal damage in human lymphocyte cultures.

Ionic (diatrizoate, ioxaglate) and nonionic (iohexol, iosimide, iopromide, and iotrolan) contrast media (CM) were evaluated for their cytogenetic effects in lymphocytes. Heparinized blood was mixed with culture medium RPMI-1640 supplemented with phytohemagglutinin, fetal calf serum, and antibiotics. Plastic tubes containing blood samples were incubated at 37 degrees C in 5% CO2 humidified air for 48 hours. To these cultures, increasing amounts of CM were added and cells incubated for an additional 24 hours. After this exposure, red blood cells were lysed with hypotonic KC1, lymphocyte smears fixed on glass slides and stained with May-Grünwald Giemsa. Chromosomal damage was analyzed by a micronucleus test. All CM tested induced micronuclei in lymphocytes quite significantly (P less than .001) when compared with the frequency of micronuclei in controls. These observations on the genotoxic potential of nonionic CM suggest that factors other than ionic composition and osmolality are involved in clastogenesis; further studies are needed to establish the molecular mechanisms in CM induced chromosomal damage.

Cytogenetic interactions of contrast media and antineoplastic drugs.

The cytogenetic interactions of ionic (diatrizoate, ioxaglate) and nonionic (iohexol) contrast media (CM) with antineoplastic drugs cyclophosphamide (CPA) and carmustine (CARM) were evaluated in a rat bone marrow cell model. Male Wistar rats were anesthetized with a 6% chloral hydrate solution and divided into five groups of five rats each. In protocol 1, there groups of rats received diatrizoate, ioxaglate, and iohexol (2.5 mL/kg) intravenously within 30 seconds. The remaining two groups were similarly injected with CPA and CARM (10mg/kg). Control animals were injected with nonpyrogenic streile water or saline solution. After 12 and 24 hours, that animals were killed with an overdose of ehloral hydrate, and bone marrow smears were prepared for determining chromosomal damage in polychromatic erytrocytes (PCEs) by a micronucleus test. In protocol 2, CPA and CARM were injected, and 15 minutes later, bolus injections of diatrizoate, ioxaglate and iohexol were given through the same route. Both ionic and nonionic CM induced significant numbers of micronuclei in PCEs (P < .05). CPA caused a severe cytogenetic effect, whereas CARM did not produce a significant number of mcronuclei in PCEs compared with control. In protocol 2 experiments, antagonism with CPA and synergism with CARM was demonstrable. Clinical limplication of the cytogenetic intractions between CM and antineoplastic drugs remains to be established.

Effect of a new nonionic contrast agent, ioxilan, on human erythrocytes and the hemostatic and serum complement pathways.

Parvez Z, Patel NB. Effect of a new nonionic contrast agent; ioxilan, on human erythrocytes and the hemostatic and serum complement pathways. Invest Radiol 1988;23(Suppl 1):S182‐S185. A new nonionic contrast medium (CM), ioxilan, was compared with iohexol and iopamidol. Following incubation of whole heparinized blood with CM, the morphology and osmotic fragility of erythrocytes were studied, the former by transmission electron microscopy. Effects on platelets and hemocoagulation were determined by standard hematologic procedures. Effects on serum complement were evaluated by measurement of total hemolytic complement (CH50), C3, C4 consumption and the presence in serums of C3c as determined by immuaoelectrophoresis. Ioxilan affected the erythrocyte membrane less than iohexol and iopamidol: the latter two produced acanthocytes, whereas ioxilan had no effect on erythrocyte morphology; also, erythrocytes exposed to ioxilan (and iopamidol) were more resilient to hypotonic saline solutions than those exposed to iohexol. In all tests, all CM showed anticoagulant activity, albeit much less when compared with ionic CM. At equal iodine concentration, ioxilan reduced the platelet aggregation and whole blood clotting time more than did iohexol. None of the CM activated the serum complement system.