PHOSPHOLIPID PEROXIDATION IN ISOLATED-PERFUSED RAT HEARTS SUBJECTED TO HYPOTHERMIA FOLLOWED BY REWARMING - INVERSE RELATION TO LOSS OF FUNCTION

In the present experimental study phospholipid peroxidation after hypo thermia and rewarming was investigated in isolated buffer-perfused rat hearts. Stable normotherm perfusion (37 degrees C) for 20 min was fol lowed by cooling to 14 degrees C, 4 h perfusion at 14 degrees C, and r ewarming to 37 degrees C followed by 30 min normotherm perfusion. Seve n hearts went through the whole protocol, whereas six hearts were subj ected only to the initial stabilization period. Mechanical performance was measured by a balloon in the left ventricle (LV) permitting measu rements of LV pressure and its derivatives. At the end of perfusion, h earts were freeze clamped in liquid nitrogen for phospholipid peroxida tion measurements, phospholipid fatty acid composition, high-energy ph osphate content (adenosine tri-, di-, and monophosphate and creatine p hosphate), and tissue water content. After rewarming there was a signi ficant reduction in mechanical performance and coronary flow. Tissue c ontent of high-energy phosphates was decreased and tissue water conten t was increased. Levels of peroxidized polyunsaturated fatty acids (co njugated diens) in phospholipids and nonesterified fatty acids were no t significantly changed (135.2 +/- 31.1 vs 74.3 +/- 7.6 nmol/g tissue dry wt and 1212 +/- 203 and 1685 +/- 197 nmol/g in control and rewarme d hearts). However, the amount of peroxidized polyunsaturated fatty ac ids in phospholipids expressed as a fraction of the phospholipids was significantly reduced by the cooling/rewarming procedure (1.28 +/- 0.2 2 vs 0.61 +/- 0.09 x 10(-3), P < 0.05). In conclusion, membrane destab ilization due to increase in phospholipid peroxidation cannot explain loss of function, loss of energy reserve, and increase in tissue water content observed after rewarming of hearts subjected to prolonged hyp othermia in combination with sustained perfusion and oxygen supply. (C ) 1994 Academic Press, Inc.