Cardiovascular effects of MnDPDP and MnCl2 in dogs with acute ischaemic heart failure.
OBJECTIVE
To examine the cardiovascular effects of MnDPDP in a model of acute heart failure in the dog, and to compare these effects with those of MnCl2.


METHODS
The study involved slow i.v. infusion of either 10, 60 and 300 mumol/kg of MnDPDP, or 1, 6 and 30 mumol/kg MnCl2, in increasing doses to groups of 5 dogs. Acute ischaemic heart failure was first induced by injection of polystyrene microspheres (50 +/- 10 microns) into the left coronary artery until a stable left ventricular end-diastolic pressure of approximately 20 mm Hg was achieved. The following test parameters were measured: left ventricular end-diastolic pressure; the first derivatives of maximum rate of left ventricular contraction and relaxation; mean aortic pressure; pulmonary artery pressure; right atrial pressure; cardiac output; heart rate; QT-time; PQ-time; QRS-width; and plasma catecholamines.


RESULTS
Slow infusion of MnDPDP at doses up to and including 12 times the clinical dose was well tolerated in dogs without further depression of cardiovascular function during acute ischaemic heart failure. At 300 mumol/kg, i.e. 60 times the human dose, only minor haemodynamic and electrophysiological effects were seen, and these were similar to those seen after administration of 30 mumol/kg MnCl2.


CONCLUSIONS
The present study suggests that slow infusion of MnDPDP should not cause further deterioration of cardiac function in patients with heart failure.
Karlsson
J O
JO
Department of Physiology and Biomedical Engineering, University of Trondheim, Norway. jogk@nycomed.com
Mortensen
E
E
Pedersen
H K
HK
Sager
G
G
Refsum
H
H
D000208:Acute Disease; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology*; D003287:Contrast Media / Q000008:administration & dosage / Q000494:pharmacology*; D003864:Depression, Chemical; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004492:Edetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008345:Manganese / Q000008:administration & dosage / Q000494:pharmacology*; D017895:Manganese Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid; C025340:manganese chloride