Iodixanol, Constriction of Medullary Descending Vasa Recta, and Risk for Contrast Medium–induced Nephropathy

Abstract

Purpose:To determine whether a type of contrast medium (CM), iodixanol, modifies outer medullary descending vasa recta (DVR) vasoreactivity and nitric oxide (NO) production in isolated microperfused DVR. Materials and Methods:Animal handling conformed to the Animal Care Committee Guidelines of all participating institutions. Single specimens of DVR were isolated from rats and perfused with a buffered solution containing iodixanol. A concentration of 23 mg of iodine per milliliter was chosen to mimic that expected to be used in usual examinations in humans. Luminal diameter was determined by using video microscopy, and NO was measured by using fluorescent techniques. Results:Iodixanol led to 52% reduction of DVR luminal diameter, a narrowing that might interfere with passage of erythrocytes in vivo. Vasoconstriction induced by angiotensin II was enhanced by iodixanol. Moreover, iodixanol decreased NO bioavailability by more than 82%. Use of 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (a superoxide dismutase mimetic) prevented both vasoconstriction with iodixanol alone and increased constriction with angiotensin II caused by CM. Conclusion:Iodixanol in doses typically used for coronary interventions constricts DVR, intensifies angiotensin II-induced constriction, and reduces bioavailability of NO. CM-induced nephropathy may be related to these events and scavenging of reactive oxygen species might exert a therapeutic benefit by preventing the adverse effects that a CM has on medullary perfusion. RSNA, 2009 Note: This copy is for your personal, non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, use the Radiology Reprints form at the end of this article. Contrast medium (CM)-induced nephropathy (CIN) is a lifethreatening complication of radiologic examinations and procedures in which an iodinated CM is used (1). In Europe and the United States, CIN accounts for more than 10% of all causes of hospital-acquired acute renal failure (2).Percutaneous coronary angiography is associated with a high risk of CIN in patients with preexisting chronic kidney disease: Roughly onehalf of these patients develop acute renal failure (3) that is associated with a 25% 1-year mortality rate (4). Several prior investigators have studied whether infusing sodium bicarbonate or scavenging reactive oxygen species (ROS) with ascorbic acid or N-acetylcysteine can prevent CIN (5-10). The intrarenal events that underlie CIN remain controversial, and the mechanism by which scavenging ROS might exert a therapeutic benefit remains to be determined.Evidence supports a high degree of vulnerability of the renal outer medulla to CM-induced damage (11). That propensity has been attributed to the nature of tubular-vascular relationships (12). Vulnerability of the thick ascending limbs to ischemic insult therefore may be an inescapable consequence of the anatomic arrangements in the outer medulla. In summary, descending vasa recta (DVR) are microvessels whose luminal diameters approach the d...

Contrast-Induced Nephropathy in Percutaneous Coronary Interventions: Pathogenesis, Risk Factors, Outcome, Prevention and Treatment

“…ROS may also deregulate the adaptive cellular mechanisms during hypoxia. A reduced synthesis of NO has been shown in isolated vasa recta perfused with CM, and the adverse effects of CM have been prevented by ROS scavengers [44]. Thus, there is an important imbalance in the regulation of vascular tone towards vasoconstriction.…”

Comparison of the Effects of Iodixanol and Iopamidol on Urine Flow, Urine Viscosity, and Glomerular Filtration in Rats

“…Pre-glomerular vasoconstriction is one reason behind CM-induced reduction in GFR [38], such as observed here upon iodixanol injection (Figure 3) [29]. Vasoconstriction of post-glomerular vessels including the descending vasa recta (DVR) will result in medullary hypoxia, and, thus, promote the vicious circle [29,39].…”

Effects of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Contrast-Induced Nephropathy

“…Medullary hypoperfusion relies on increased resistance to blood flow, due to, descending vasa recta vasoconstriction, among other factors. In both the cortex and the medulla, CM can shift the balance between vasodilatory and vasoconstrictive factors towards vasoconstriction [16,17]. Because medullary perfusion comprises <10% of total renal blood flow, the vasoconstrictive response of total renal blood flow to CM observed in several studies reflects cortical rather than medullary effects.…”

“…Larson et al [22] have successfully induced acute renal failure in animal models by administration of a contrast media bolus, and they found that sodium depletion accentuated both the magnitude and duration of the vasoconstrictive phase of the renal blood flow response to the injection of contrast medium and that blockade of the intrarenal renin-angiotensin system shortened the duration of this response. In addition, there is evidence that iodixanol, a nonionic, dimeric contrast media, causes increased oxidative stress and decreased nitric oxide production in outer medullary descending vasa recta, with consequent constriction of the descending vasa recta and increased reactivity to angiotensin II [16]. Activation of RAAS could also cause vasoconstriction of the efferent glomerular arteriole while simultaneously increasing the ex novo synthesis of vasodilator prostaglandins resulting in nearly stable or slightly increased intrarenal resistance.…”