Propofol enhances ischemic tolerance of middle-aged rat hearts: effects on 15-F(2t)-isoprostane formation and tissue antioxidant capacity

Cardiovasc Res. 2003 Jul 1;59(1):113-21. doi: 10.1016/s0008-6363(03)00351-1.

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 microg/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 microl/min. Propofol in KH was perfused at 12 microg/ml for the first 15 min of reperfusion and subsequently reduced to 5 microg/ml in propofol treatment groups. Coronary effluent was assayed for 15-F(2t)-isoprostane after equilibration, during ischemia (T(1)) and at 0.5 (T(2)) and 5 (T(3)) min of reperfusion. After 90 min of reperfusion (T(4)), 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-F(2t)-isoprostane levels in P-M and P-Y than in C-M and C-Y at T(1). At T(4), 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Antioxidants / metabolism
  • Antioxidants / therapeutic use*
  • Disease Susceptibility
  • Male
  • Myocardial Ischemia / metabolism
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / metabolism
  • Oxidants / pharmacology
  • Perfusion
  • Propofol / metabolism
  • Propofol / therapeutic use*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Thiobarbituric Acid Reactive Substances / analysis
  • tert-Butylhydroperoxide / pharmacology

Substances

  • Antioxidants
  • Oxidants
  • Thiobarbituric Acid Reactive Substances
  • tert-Butylhydroperoxide
  • Propofol