Control of myocardial catecholamine release during acute ischemia.
Regional myocardial catecholamine release during graded stimulation of the left ansa subclavia has been assessed in open-chest anaesthetised dogs during left anterior descending coronary artery (LAD) occlusion and reperfusion. Frequency-dependent release of noradrenaline (NA) in response to stimulation of the ansa was maintained across the ischaemic area during the two early phases of enhanced vulnerability to arrhythmias at 5 and 17 min, but was selectively inhibited after 30 min. Spontaneous NA release from the ischaemic heart did not occur with either alpha 2-adrenoceptor (yohimbine) or neuronal reuptake (desmethylimipramine) blockade alone, but was unmasked by the drug combination. Intracoronary potassium infusions, designed to mimic the concentration range seen in ischaemia, exerted biphasic effects on stimulation-induced NA release, being inhibitory at low dose and stimulatory at high dose. High-dose intracoronary adenosine inhibited NA release in response to high-frequency ansa stimulation but basal release was slightly increased. Thus, catecholamine release from ischaemic myocardium has multifactorial determinants and may be limited by enhanced reuptake, adrenoceptor-mediated negative feedback, and metabolite accumulation. Lack of nerve-terminal response to sympathetic stimulation coincides with the later period of myocardial electrical stability.
J C
JC
Forfar
D C
DC
Russell
R A
RA
Riemersma
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000294:innervation; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D009435:Synaptic Transmission; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D000241:Adenosine; D011188:Potassium; D003891:Desipramine; D009638:Norepinephrine