European Journal of Cardio-Thoracic Surgery, Vol 1, 80-90, Copyright © 1987 by European Association for Cardio-thoracic Surgery
Free radicals and cardioplegia: the absence of an additive effect with allopurinol pretreatment and the use of antioxidant enzymes in the rat
DJ Chambers, MV Braimbridge and DJ Hearse
Rayne Institute, St. Thomas Hospital, London, UK.
The isolated perfused working rat heart model of cardiopulmonary bypass was
used to assess whether (a) allopurinol pretreatment enhances resistance to
normothermic (30 min) or hypothermic (4 h) ischemia; (b) addition of
antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) to
cardioplegic and/or reperfusion solutions are protective; (c) any
protective effects are additive. With normothermic ischemia, allopurinol
pretreatment improved recovery of aortic flow from its control value of 25
+/- 3% to 48 +/- 6% (P less than 0.05). Similarly, SOD plus CAT used during
both ischemia and reperfusion improved recovery of aortic flow from a
control value of 28 +/- 4% to 48 +/- 6% (P less than 0.05). However,
various combinations of the two types of intervention afforded no additive
protection. Under hypothermic (21 degrees C) conditions, allopurinol
pretreatment was not effective, whereas SOD and CAT added during ischemia
and reperfusion improved recovery of aortic flow from its control value of
53 +/- 4% to 69 +/- 5% (P less than 0.05). This value was similar to
allopurinol pretreatment and SOD plus CAT added during ischemia and
reperfusion (69 +/- 6%: P less than 0.05). These results provide further
evidence that reperfusion-induced free radical formation may adversely
affect postischemic recovery of function. The absence of an additive effect
suggests a common mechanism of action, which is likely to involve the free
radical-generating enzyme xanthine oxidase; however, other mechanisms may
exist. Our results further support the use of antifree radical intervention
in conjunction with cardioplegia to protect the heart during ischemia and
reperfusion.
