Time Course and Mechanism of Myocardial Catecholamine Release During Transient Ischemia In Vivo
BACKGROUND: Elevated concentrations of norepinephrine (NE) have been observed in ischemic myocardium. We investigated the magnitude and mechanism of catecholamine release in the myocardial interstitial fluid (MIF) during ischemia and reperfusion in vivo through the use of microdialysis. METHODS AND RESULTS: In 9 anesthetized pigs, interstitial catecholamine concentrations were measured in the perfusion areas of the left anterior descending coronary artery (LAD) and the left circumflex coronary artery. After stabilization, the LAD was occluded for 60 minutes and reperfused for 150 minutes. During the final 30 minutes, tyramine (154 nmol. kg(-1). min(-1)) was infused into the LAD. During LAD occlusion, MIF NE concentrations in the 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, respectively. Local uptake-1 blockade attenuated release of all 3 catecholamines by >50%. During reperfusion, MIF catecholamine concentrations returned to baseline within 120 minutes. At that time, the tyramine-induced NE release was similar to that seen in nonischemic control animals despite massive infarction. Arterial and MIF catecholamine concentrations in the left circumflex 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 neuronal 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.
|Keywords||Animals, Blood Pressure/physiology, Coronary Circulation/physiology, Female, Heart Rate/physiology, Heart/innervation/physiology, Male, Microdialysis, Myocardial Infarction/*metabolism/physiopathology, Myocardial Ischemia/*metabolism/physiopathology, Myocardial Reperfusion, Nerve Endings/metabolism, Norepinephrine/*metabolism, Research Support, Non-U.S. Gov't, Stroke Volume/physiology, Swine, Sympathetic Nervous System/drug effects/*metabolism, Sympathomimetics/pharmacology, Tyramine/pharmacology, Ventricular Fibrillation/metabolism|
Lameris, Th.W., de Zeeuw, P.A., Alberts, G., Boomsma, F., Duncker, D.J.G.M., Verdouw, P.D., … Man in 't Veld, A.J.. (2000). Time Course and Mechanism of Myocardial Catecholamine Release During Transient Ischemia In Vivo. Circulation (Baltimore), 101(22), 2645–2650. Retrieved from http://hdl.handle.net/1765/9379