Local Release of Myocardial Norepinephrine During Acute Ischemia

Abstract

The appearance of an early ischemia-induced local release of myocardial norepinephrine (NE) was examined in the isolated Langendorff-perfused rat heart prelabeled with [³H]NE. Either glucose or lactate was used as the perfusion substrate. Ischemia for a 60-min period was produced by global flow reduction (by 90%) or left coronary artery ligation followed by a 15-min reperfusion period. During the first 20 min of ischemia both the concentration of [³H]NE and the fraction of total ³H representing nonmetabolized [³H]NE were increased in the coronary venous effluent. This early increase in [³H]NE concentration was most pronounced in hearts with global ischemia perfused with lactate as substrate (from 19 ± 2 to 524 ± 76 fmol/ml/g after 20 min of ischemia). The quantity of [³H]NE released was then further increased during the 60-min period of ischemia. Reperfusion of the ischemic myocardium was associated with a marked outflow of [³H]NE and [³H]NE metabolites, primarily representing a washout from the ischemic tissue. Under the present experimental conditions the ischemia-induced release of NE was attenuated by glucose, probably owing to an ongoing glycolytic ATP formation. This effect was most pronounced during global low-flow ischemia. It is concluded that ischemia is associated with a local release of myocardial NE. In the nonworking Langendorff heart preparation, clear evidence of such a local release was already obtained after 10–20 min of ischemia.