Cardioprotective effects of the MR contrast agent MnDPDP and its metabolite MnPLED upon reperfusion of the ischemic porcine myocardium

Abstract

MnPLED seems to reduce reperfusion-induced cardiac dysfunction and infarct size in pigs. MnDPDP does not reduce infarct size in the pig, probably because of the rapid exchange of Mn2+ for Zn2+ taking place in the pig.

Uptake of MnCl2 and mangafodipir trisodium in the myocardium: A magnetic resonance imaging study in pigs

“…Manganese ions need to be dissociated from their ligand in order to be taken up by the myocardial cells (13). In pigs the main mechanism for dissociating Mn 2ϩ -ions from Mn-DPDP is transmetallation of the Mn 2ϩ -ions for Zn 2ϩ in the DPDP molecule, while in, for example, humans and rats a large part of the Mn-DPDP is instead metabolized in the liver into manganese dipyroxidyl diamine (Mn-PLED) (17,20,21). Because of this, the intracellular contrast effect of Mn-DPDP is limited by the amount of Zn 2ϩ -ions in the blood and the speed at which the transmetallation occurs.…”

MR Contrast Agents for Cardiac Imaging

“…Interestingly, recent experimental studies in pigs revealed that the metabolite from Mn-DPDP namely manganese dipyridoxyl ethyldiamine (MnPLED) could reduce postischemic reperfusion-induced cardiac dysfunction and infarct size (Karlsson et al 2001). Therefore, the use of a Mn 2+ -releasing contrast agents such as Mn-DPDP may be a promising multipurpose approach.…”

“…Similar approach has been adopted in cardiac MRI using cold cation Mn 2+ preparations as intracellular contrast agents for infarct imaging, since Mn 2+ is potent for T1 shortening and is taken up only in cells capable of active calcium (Ca 2+ ) transport, and thereby provides an analog to 201 Tl imaging in cardiac scintigraphy (Bremerich et al 2000;Karlsson et al 2001;Flacke et al 2003;Storey et al 2003;Krombach et al 2004). Mn 2+ has an ionic radius similar to that of Ca 2+ and is known to enter myocytes via voltage-facilitated calcium channels.…”

Fodipir and Its Dephosphorylated Derivative Dipyridoxyl Ethyldiamine Are Involved in Mangafodipir-Mediated Cytoprotection against 7β-Hydroxycholesterol-Induced Cell Death

“…Correspondingly, in this study, we found that MnPLED and Dp-dp significantly decreased 7β-OH-induced ROS production. SOD mimetic activity of MnPLED [11] may account for this decline in ROS production in cells exposed to 7β-OH. We tested this hypothesis by measuring the levels of MnSOD in cells exposed to MnPLED and Dp-dp.…”

“…It has also been reported that a metabolite of mangafodipir, MnPLED, possesses SOD-like activity and has potential to reduce oxidative injuries in the heart [11]. Additionally, fodipir (Dp-dp) has a metal ion-chelating effect, which also might contribute to the anti-oxidant property.…”