ABSTRACT
PURPOSE: To study potential properties of iodinated radiographic contrast media (IRCM) for intravascular use in in vitro free radical generating reactions. MATERIAL AND METHODS: Superoxide (*O2-) and hydroxyl (*OH) radicals were generated in xanthine oxidase and Fenton reactions. *O2- was assayed by the nitroblue tetrazolium (NBT) method, whereas *OH was assayed by an aromatic hydroxylation (2-hydroxybenzoic acid) method. Total antioxidant status (TAS) of test substances was determined by a colorimetric assay. Finally, acetyl-cholinesterase (AChE) activity was measured in the absence and presence of IRCM. RESULTS: High concentrations (>50 mM) of IRCM inhibited *O2- production, ionic more than non-ionic IRCM. Medium concentrations (25-50 mM) of IRCM reduced *OH production, and both types of IRCM were equally potent. Low concentrations (<25 mM) of non-ionic IRCM displayed higher antioxidant capacity than their ionic counterparts when tested in the TAS assay. Visipaque 320 (iodixanol) was found to have the highest TAS value, followed by Omnipaque 350 (iohexol), Hexabrix 320 (ioxaglate), and Urografin 370 (diatrizoate). CONCLUSION: IRCM have in vitro antioxidant properties in concentrations relevant for their clinical application. These properties may therefore be of potential importance when evaluating IRCM effects in vivo, particularly those concerning cardiovascular and renal function.
Subject(s)
Acetylcholinesterase/chemistry , Contrast Media/chemistry , Hydrogen Peroxide/chemistry , Iron/chemistry , Reactive Oxygen Species/chemical synthesis , Triiodobenzoic Acids/chemistry , Xanthine Oxidase/chemistry , Colorimetry , Drug Interactions , In Vitro Techniques , Oxidation-ReductionABSTRACT
The aim of the present study was to investigate the role of the Na+/K+/2Cl- co-transporter and the Na+/H+ exchanger on contractile function and electrolyte regulation during hyperosmotic perfusion of the heart. Langendorff perfused rat hearts were subjected to hyperosmolal perfusion in 10-min intervals. Perfusates were made hyperosmotic by adding mannitol to the buffer (370, 450 and 600 mOsmol/kg H2O). Cardiac contractile function was monitored with a balloon in the left ventricle (LV) coupled to a pressure transducer. Cardiac effluent was sampled repeatedly throughout and after hyperosmotic perfusion and analysed for content of Na+, K+, and Cl-. All three hyperosmotic perfusates initially reduced LV developed pressure (LVDP), but for 370 and 450 mOsmol/kg H2O, LVDP recovered to baseline within 4 min of perfusion. With 600 mOsmol/kg H2O, LVDP recovered slowly and was 50% below baseline after 10 min of hyperosmotic perfusion. Inhibition of the Na+/H+ exchanger with 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and 3-methylsulfonyl-4-piperidinobenzoyl-guanidine methanesulfonate (HOE 694) abolished the recovery of LVDP to the 600 mOsmol/kg H2O perfusate, whereas inhibition of the Na+/K+/2Cl- co-transporter had no impact on LVDP. Potassium was taken up by the heart during hyperosmotic perfusion and this uptake was significantly reduced with inhibition of the Na+/H+ exchanger. Intracellular pH was assessed with 31p magnetic resonance spectroscopy and hyperosmolality induced a significant alkalosis that was dependent upon the Na+/H+ exchanger. The rat heart responds to moderate elevations in osmolality with a transient reduction in contractile function, whereas an elevation of 300 mOsmol/kg H2O persistently reduces contractile function. The Na+/H+ exchanger, but not the Na+/K+/2Cl- co-transporter, is of importance in contractile recovery and electrolyte regulation during hyperosmotic perfusion in the rat heart.
Subject(s)
Chloride Channels/physiology , Heart/physiology , Sodium-Hydrogen Exchangers/physiology , Sodium-Potassium-Exchanging ATPase/physiology , Animals , Hydrogen-Ion Concentration , Male , Myocardial Contraction , Osmosis , Perfusion , Rats , Rats, Sprague-Dawley , Water-Electrolyte BalanceABSTRACT
PURPOSE: Despite detailed knowledge of the effects of X-ray contrast media on cardiac function, no studies have examined the effect of contrast media injections on the subsequent tolerance to ischemia in the heart. METHODS: Isolated perfused rat hearts were exposed to repetitive injections of iohexol, iodixanol, or ioxaglate before 30 min of global ischemia and 120 min of reperfusion. These groups were compared with control (no pretreatment) and ischemic preconditioning known to reduce infarct size. Physiologic variables and infarct size were measured RESULTS: Pretreatment with iodixanol reduced infarct size significantly compared with control and thus afforded protection against ischemia. Injections with iohexol and ioxaglate reduced infarct size, although not significantly, compared with control. CONCLUSION: Pretreatment of the isolated rat heart with commonly used contrast media enhances the cardiac tolerance to subsequent ischemia. The mechanism behind this protective effect could not be determined, but could involve stretching of the heart and/or generation of nitric oxide.
