Brief repetitive ischemia: effect on norepinephrine release, arrhythmias, and functional recovery in isolated perfused rat heart

The objective of the present study was to determine norepinephrine release, functional recovery, and incidence of arrhythmias following multiple episodes of brief (5 min) ischemia and to compare these variables with those obtained after continuous ischemia (30 min) in isolated rat hearts perfused with modified Krebs-Henseleit solution. Left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and cardiac rhythm were continuously recorded. The amount of norepinephrine in perfusate was measured by high-performance liquid chromatography. The data showed no increases in LVEDP during the six successive 5-min periods of ischemia interrupted by 5-min reperfusion. The six repetitive periods of reperfusion after repetitive 5-min periods of ischemia were associated with a restoration of left ventricular diastolic function and preservation of reactive hyperemia (23.3 +/- 1.5 mL/min vs. baseline 16.5 +/- 1.3 mL/min; p < 0.05). The incidences of ventricular fibrillation (VF) (10/10) and ventricular tachycardia (VT) (10/10) upon reperfusion in the continuous ischemia group were higher than those in the repetitive ischemia group (VF, 2/10; VT, 3/10; p < 0.05). Norepinephrine washout upon reperfusion after 30-min continuous ischemia was 58.2 +/- 17.4 ng/g of heart, but no increase in norepinephrine washout was observed after brief repetitive ischemic episodes (11.2 +/- 2.4 ng/g of heart) (p < 0.05). Our results show a substantial release of norepinephrine only after 30 min of continuous ischemia, in the isolated rat heart.