In general, iodinated contrast media (CM) are tolerated well, and CM use is steadily increasing. Acute kidney injury is the leading life-threatening side effect of CM. Here, we highlight endpoints used to assess CM-induced acute kidney injury (CIAKI), CM types, risk factors, and CIAKI prevention. Moreover, we put forward a unifying theory as to how CIAKI comes about; the kidney medulla's unique hyperosmolar environment concentrates CM in the tubules and vasculature. Highly concentrated CM in the tubules and vessels increases fluid viscosity. Thus, flow through medullary tubules and vessels decreases. Reducing the flow rate will increase the contact time of cytotoxic CM with the tubular epithelial cells and vascular endothelium, and thereby damage cells and generate oxygen radicals. As a result, medullary vasoconstriction takes place, causing hypoxia. Moreover, the glomerular filtration rate declines due to congestion of highly viscous tubular fluid. Effective prevention aims at reducing the medullary concentration of CM, thereby diminishing fluid viscosity. This is achieved by generous hydration using isotonic electrolyte solutions. Even forced diuresis may prove efficient if accompanied by adequate volume supplementation. Limiting the CM dose is the most effective measure to diminish fluid viscosity and to reduce cytotoxic effects.

The cerebral hyperaemia is one of the fundamental mechanisms for the central nervous system homeostasis. Due also to this mechanism, oxygen and nutrients are maintained in satisfactory levels, through vasodilation and vasoconstriction. The brain hyperaemia, or coupling, is accomplished by a group of cells, closely related to each other; called neurovascular unit (NVU). The neurovascular unit is composed by neurones, astrocytes, endothelial cells of blood-brain barrier (BBB), myocytes, pericytes and extracellular matrix components. These cells, through their intimate anatomical and chemical relationship, detect the needs of neuronal supply and trigger necessary responses (vasodilation or vasoconstriction) for such demands. Here, we review the concepts of NVU, the coupling mechanisms and research strategies.

1. The present review focuses on the cytotoxic effects of iodinated contrast media (CM) that are shared by all types of CM. 2. Although the clinical nephrotoxicity of CM has been progressively improved, all currently available CM still possess a level of cytotoxicity, which is probably caused by iodine. 3. The toxicity caused by specific CM properties, such as osmolarity, viscosity and ionic strength, can be differentiated from the cytotoxicity common to all CM in studies using cell culture, isolated blood vessels and isolated tubules. 4. The cytotoxicity induced by CM leads to apoptosis and cell death of endothelial and tubular cells and may be initiated by cell membrane damage, together with oxidative stress. 5. Cell damage may be aggravated by factors such as tissue hypoperfusion and hypoxia, properties of individual CM, such as ionic strength, high osmolarity and/or viscosity, and clinically unfavourable conditions. 6. Clinically detectable renal failure may result from the summation of all these factors.

Artificial oxygen carriers, favorably hemoglobin-based oxygen carriers (HBOCs), are being investigated intensively during the last 30 years with the aim to develop a universal blood substitute. However, serious side effects mainly caused by vasoconstriction triggered by nitric oxide (NO) scavenging due to penetration of nanosized HBOCs through the endothelial gaps of the capillary walls and/or oxygen oversupply in the precapillary arterioles due to their low oxygen affinity led to failure of clinical trials and FDA disapproval. To avoid these effects, HBOCs with a size between 100 and 1000 nm and high oxygen affinity are needed. Here we present for the first time unique hemoglobin particles (HbPs) of around 700 nm with high oxygen affinity and low immunogenicity using a novel, highly effective, and simple technique. The fabrication procedure provides particles with a narrow size distribution and nearly uniform morphology. The content of hemoglobin (Hb) in the particles corresponded to 80% of the Hb content in native erythrocytes. Furthermore, we demonstrate a successful perfusion of isolated mouse glomeruli with concentrated HbP suspensions in vitro. A normal, nonvasoconstrictive behavior of the afferent arterioles is observed, suggesting no oxygen oversupply and limited NO scavenging by these particles, making them a highly promising blood substitute.

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...