Time course and mechanism of myocardial catecholamine release during transient ischemia in vivo

Background-Elevated concentrations of norepinephrine (NE) have been observe d in ischemic myocardium. We investigated the magnitude and mechanism of ca techolamine release in the myocardial interstitial fluid (MIF) during ische mia and reperfusion in vivo through the use of microdialysis, Methods and Results-In 9 anesthetized pigs, interstitial catecholamine conc entrations were measured in the perfusion areas of the left anterior descen ding coronary artery (LAD) and the left circumflex coronary artery. After s tabilization, the LAD was occluded for 60 minutes and reperfused for 150 mi nutes. During the final 30 minutes, tyramine (154 nmol . kg(-1) . min(-1)) was infused into the LAD. During LAD occlusion, MIF NE concentrations in th e ischemic region increased progressively from 1.0+/-0.1 to 524+/-125 nmol/ L. MIF concentrations of dopamine and epinephrine rose from 0.4+/-0.1 to 43 .9+/-9.5 nmol/L and from <0.2 (detection limit) to 4.7+/-0.7 nmol/L, respec tively. Local uptake-1 blockade attenuated release of all 3 catecholamines by >50%. During reperfusion, MIF catecholamine concentrations returned to b aseline within 120 minutes. At that time, the tyramine-induced NE release w as similar to that seen in nonischemic control animals despite massive infa rction, Arterial and MIF catecholamine concentrations in the left circumfle x coronary artery region remained unchanged. Conclusions-Myocardial ischemia is associated with a pronounced increase of MIF catecholamines, which is at least in part mediated by a reversed neuro nal reuptake mechanism. The increase of MIF epinephrine implies a (probably neuronal) cardiac source, whereas the preserved catecholamine response to tyramine in postischemic necrotic myocardium indicates functional integrity of sympathetic nerve terminals.