Do alterations in prostanoid or catecholamine release influence the antiarrhythmic activity of nicergoline?
We examined the effects of nicergoline, an alpha-adrenoceptor blocking drug and an inhibitor of platelet phospholipase, on haemodynamics, blood gases, cardiac arrhythmias, and prostanoid and catecholamine release in anaesthetised greyhounds before, during, and after a 40-min occlusion of the left anterior descending coronary artery. Twenty-five minutes after commencing the intravenous infusion of nicergoline (50 micrograms kg-1 min-1) there were significant reductions in heart rate, arterial blood pressure, left ventricular dP/dtmax, and cardiac output. Nicergoline also increased the 0(2) extraction by the myocardium both before and during coronary artery occlusion. In contrast to control animals, heart rate decreased but there were no further reductions in arterial blood pressure during the occlusion period. Nicergoline improved survival (from 17 in control dogs to 50%) following the combined period of myocardial ischaemia and reperfusion and appeared to suppress the phase 1b occlusion-induced arrhythmias. The release of thromboxane B2 from the ischaemic myocardium was partially suppressed by nicergoline, and the ratio of 6-keto PGF1 alpha/thromboxane B2 (the stable breakdown products of prostacyclin and thromboxane A2, respectively) was increased. The washout of noradrenaline and adrenaline from the ischaemic myocardium following release of the occlusion was slightly enhanced by nicergoline. It is concluded that the beneficial metabolic and prostacyclin-promoting properties of nicergoline may be opposed by its action on noradrenaline washout, thus limiting its antiarrhythmic effectiveness.
F M
FM
Williams
S J
SJ
Coker
H G
HG
Dean
K A
KA
Kane
J R
JR
Parratt
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001157:Arterial Occlusive Diseases / Q000503:physiopathology; D001784:Blood Gas Analysis; D003326:Coronary Circulation; D004285:Dogs; D004298:Dopamine / Q000097:blood*; D004837:Epinephrine / Q000097:blood*; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009530:Nicergoline / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood*; D010477:Perfusion; D011453:Prostaglandins / Q000097:blood*; D013929:Thromboxane B2 / Q000097:blood
D000889:Anti-Arrhythmia Agents; D004873:Ergolines; D011453:Prostaglandins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D009530:Nicergoline; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine