Propofol enhances ischemic tolerance of middle-aged rat hearts: Effects on 15-F2t-isoprostane formation and tissue antioxidant capacity

Abstract

Objective: Experimental study has shown that myocardial ischemic tolerance is reduced during middle-age. We investigated the effect of propofol on ischemic tolerance of middle-aged rat hearts. Methods: Hearts of young adult (10 weeks old, Y) and middle-aged rats (20 weeks old, M) were assigned to propofol (P-Y, P-M) and control (C-Y, C-M) groups (n=6 each). Hearts were perfused using a Langendorff preparation with Krebs-Henseleit solution (KH) at constant flow rates. We applied propofol (P-Y, P-M) for 10 min at 12 μg/ml before inducing 40 min global ischemia. During ischemia, saline (C-Y, C-M) or propofol (P-Y, P-M) in saline was perfused through the aorta at 60 μl/min. Propofol in KH was perfused at 12 μg/ml for the first 15 min of reperfusion and subsequently reduced to 5 μg/ml in propofol treatment groups. Coronary effluent was assayed for 15-F2t-isoprostane after equilibration, during ischemia (T1) and at 0.5 (T2) and 5 (T3) min of reperfusion. After 90 min of reperfusion (T4), hearts were harvested to assess tissue antioxidant capacity. Results: In P-Y, we observed an increased latency to ischemic-contracture and a significantly reduced contracture after 35 min ischemia compared to control groups. No ischemic contracture was observed in P-M. There were significantly lower 15-F2t-isoprostane levels in P-M and P-Y than in C-M and C-Y at T1. At T4, the recovery of left ventricular developed pressure in P-M was greater than in P-Y (P<0.05); both were greater than in C-M and C-Y. Conclusion: Propofol enhanced ischemic tolerance of middle-aged hearts, primarily by inhibiting lipid peroxidation. © 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.