Antithrombotic Effects of Ionic and Non-ionic Contrast Media in Nonhuman Primates

Abstract

SummaryThromboembolic complications have been attributed to the use of radiographic contrast media (CM) during interventional procedures for arterial revascularization. However, due to the low frequency of adverse events, comparisons between different CM have been difficult to perform, although it has been suggested that ionic (vs. non-ionic) CM may be associated with fewer thrombotic events. The present study was undertaken using well-characterized baboon thrombosis models in order to compare different CM under physiologically relevant and controlled conditions of blood flow, exposure time, and CM concentration. Three CM were studied: ioxaglate, iohexol, and iodixanol. CM were locally infused into the proximal segment of femoral arteriovenous shunts. Palmaz-Schatz stents (4 mm i.d.) and expanded tubular segments (9 mm i.d.), which exhibited venous-type flow recirculation and stasis, were deployed into the shunts distally. Saline was infused in identical control studies. Blood flow was maintained at 100 ml/min. Thrombosis was measured over a blood exposure period of 2 hours by gamma camera imaging of 111In-platelets and by gamma counting of deposited 125I-fibrin. CM concentrations within the flowfield were predicted using computational fluid dynamics. At infusion rates of 0.1 and 0.3 ml/min, the low-osmolar ionic CM ioxaglate reduced both platelet and fibrin deposition on the stents by 75-80% (p <0.005), while both iohexol and iodixanol reduced platelet deposition by 30-50% (p <0.05). In the regions of low shear flow, ioxaglate (0.3 ml/min) also reduced platelet deposition significantly (by 52% vs. control results; p <0.05). Thus the three agents evaluated – ioxaglate, iohexol, and iodixanol – all produced anticoagulant and antiplatelet effects and were inherently antithrombotic in vivo. The most striking effects were seen with the low osmolarity, ionic contrast agent ioxaglate.

Intra-Arterial Iodinated Radiographic Contrast Material Injection Administration in a Rat Middle Cerebral Artery Occlusion and Reperfusion Model

“…Nonionic low-osmolar IRCMs and isosmolal iodixanol permit greater thrombin generation and platelet and fibrin deposition in animal models 39–43 than ionic ioxaglate. Increased local thrombus formation during coronary intervention in humans occurs with nonionic compared with ionic low-osmolar contrast material.…”

The assessment of thrombotic markers utilizing ionic versus non‐ionic contrast during coronary angiography and intervention trial

“…An in vitro model by Corot et al demonstrated increased thrombin time with ioxaglate, iohexol, and iodixanol compared to saline controls . Similarly, in a baboon thrombosis model, all three agents were inherently antithrombotic compared to stents infused with saline . However, in these studies, ioxaglate was associated with a thrombin time more than five times that with iodixanol.…”

“…However, in these studies, ioxaglate was associated with a thrombin time more than five times that with iodixanol. Ioxaglate was also associated with a lower amount of fibrin deposition on stents compared with iohexol, which in turn was associated with a lower amount of fibrin deposition than iodixanol . In an in vitro model conducted by Jones et al, no thrombi were formed when blood was mixed with ioxaglate, while thrombi formed with iohexol weighed less than those formed with iodixanol .…”

The effects of non-ionic contrast medium on the hemorheology in vitro and in vivo

“…The loss of plasma proteins would result in the decrease of whole blood viscosity. (3) contrast media was reported to decrease the erythrocyte aggregation in vivo [1,4,10], which would decrease the whole blood viscosity.…”