SPECTROSCOPIC AND METABOLIC EFFECTS OF MNCL2 AND MNDPDP ON THE ISOLATED AND PERFUSED RAT-HEART

RATIONALE AND OBJECTIVES. Several works have shown that the hepatobili ary magnetic resonance imaging contrast agent manganese dipyridoxyl di phosphate (MnDPDP) partly releases its metallic ion and exhibits cardi ovascular effects that are supposed to arise from the free manganese i ons (Mn++). In the current study, the cellular internalization of Mn b y the isolated rat heart is monitored through the mechanical function of the organ and the relative broadening of the P-31 nuclear magnetic resonances, METHODS. Rat hearts were perfused with manganese chloride (MnCl2; 15 and 25 mu M) or MnDPDP (25 mu M). Variations of the linewid ths, heights, and surfaces of phosphocreatine and adenosine triphospha te peaks were monitored, Cardiac function was monitored simultaneously through heart rate, left ventricular pressure, and coronary flow, RES ULTS. Influx of Mn++ induces a significant broadening of the P-31 reso nances of adenosine triphosphate and phosphocreatine because of a stro ng scalar paramagnetic interaction between the nuclei and the ion, Com pared with MnDPDP administered at the same concentration, MnCl2 induce d a more pronounced and dose-dependent line broadening as well as a co ronary vasodilation, Calcium channel blockers (nifedipine and verapami l) and EDTA inhibit MnCl2 influx, Similarly, verapamil, EDTA, and DPDP reduce the alterations provoked by MnDPDP. CONCLUSIONS. The effects o f MnDPDP are smaller but of the same type than those induced by MnCl2, Their inhibition by calcium channel blockers (verapamil and nifedipin e) and by an excess of strong chelators such as DPDP or EDTA confirms that they originate from a partial release of Mn++ by the contrast age nt.