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Cardiovascular Research 2003 59(1):113-121; doi:10.1016/S0008-6363(03)00351-1
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

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

Zhengyuan Xiaa, David V. Godina and David M. Ansleya,b,*

aCentre for Anesthesia and Analgesia, Department of Pharmacology and Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada
bDepartment of Anesthesia, The University of British Columbia, Room 3200, 3rd Floor, JPP, 910 West 10th Ave., Vancouver, BC, V5Z 4E3, Canada

daansley{at}interchange.ubc.ca

* Corresponding author. Tel.: +1-604-875-4575; fax: +1-604-875-5344.

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.

KEYWORDS Ischemia; Free radicals; Aging; Reperfusion; Myocardium; Propofol


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