Spectroscopic and metabolic effects of MnCl2 and MnDPDP on the isolated and perfused rat heart.
OBJECTIVE
Several works have shown that the hepatobiliary magnetic resonance imaging contrast agent manganese dipyridoxyl diphosphate (MnDPDP) partly releases its metallic ion and exhibits cardiovascular effects that are supposed to arise from the free manganese ions (Mn++). In the current study, the cellular internalization of Mn by 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 microM) or MnDPDP (25 microM). Variations of the linewidths, heights, and surfaces of phosphocreatine and adenosine triphosphate peaks were monitored. Cardiac function was monitored simultaneously through heart rate, left ventricular pressure, and coronary flow.


RESULTS
Influx of Mn++ induces a significant broadening of the P-31 resonances of adenosine triphosphate and phosphocreatine because of a strong scalar paramagnetic interaction between the nuclei and the ion. Compared with MnDPDP administered at the same concentration, MnCl2 induced a more pronounced and dose-dependent line broadening as well as a coronary vasodilation. Calcium channel blockers (nifedipine and verapamil) and EDTA inhibit MnCl2 influx. Similarly, verapamil, EDTA, and DPDP reduce the alterations provoked by MnDPDP.


CONCLUSIONS
The effects of MnDPDP are smaller but of the same type than those induced by MnCl2. Their inhibition by calcium channel blockers (verapamil and nifedipine) 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 agent.
Vander Elst
L
L
Department of Organic Chemistry, University of Mons-Hainaut, Mons, Belgium.
Colet
J M
JM
Muller
R N
RN
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002712:Chlorides / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017895:Manganese Compounds / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017725:Ventricular Pressure / Q000187:drug effects
D002712:Chlorides; D017895:Manganese Compounds; D010725:Phosphocreatine; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid; C025340:manganese chloride