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J Thorac Cardiovasc Surg 2003;125:625-632
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Deep hypothermic circulatory arrest and global reperfusion injury: Avoidance by making a pump prime reperfusate—A new concept

From the Division of Cardiovascular Surgery, University of California at Los Angeles Medical Center, Los Angeles, Calif, and The Heart Institute for Children, Hope Children's Hospital, Oak Lawn, Ill.

Read at the Eighty-first Annual Meeting of The American Association for Thoracic Surgery, San Diego, Calif, May 6-9, 2001.

Received for publication May 16, 2001. Revisions requested July 18, 2001; revisions received Sept 19, 2001. Accepted for publication Oct 2, 2001. Address for reprints: Bradley S. Allen, MD, The Heart Institute for Children, Hope Children's Hospital, 4440 West 95th St, Oak Lawn, IL 60453 (E-mail: bradallen{at}thic.com).

Objective: We sought to determine whether damage after deep hypothermic circulatory arrest can be diminished by changing pump prime components when reinstituting cardiopulmonary bypass.
Methods: Fifteen piglets (2-3 months old) were cooled to 19°C by using the alpha-stat pH strategy. Five were cooled and rewarmed without ischemia (control animals), and the other 10 piglets underwent 90 minutes of deep hypothermic circulatory arrest. Of these, 5 were rewarmed and reperfused without altering the cardiopulmonary bypass circuit blood prime. In the other 5 animals, the bypass blood prime was modified (leukocyte depleted, hypocalcemic, hypermagnesemic, pH-stat, normoxic, mannitol, and an Na⁺/H⁺ exchange inhibitor) during circulatory arrest before starting warm reperfusion. Oxidant injury was assessed on the basis of conjugated dienes, vascular changes on the basis of endothelin levels, myocardial function on the basis of cardiac output and dopamine need, lung injury on the basis of pulmonary vascular resistance and oxygenation, and cellular damage on the basis of release of creatine kinase and aspartate aminotransferase. Neurologic assessment (score 0, normal; score 500, brain death) was done 6 hours after discontinuing cardiopulmonary bypass.
Results: Compared with animals undergoing cardiopulmonary bypass without ischemia (control animals), deep hypothermic circulatory arrest without modification of the reperfusate produced an oxidant injury (conjugated dienes increased 0.78 vs 1.71 absorbance (Abs) 240 nmol/L per 0.5 mL, P < .001 vs control animals), depressed cardiac output (6.0 vs 4.0 L/min, P < .05 vs control subjects), prolonged dopamine need (P < .001 vs control subjects), elevated pulmonary vascular resistance (74% vs 197%, P < .05 vs control subjects), reduced oxygenation (P < .01 vs control subjects), increased neurologic injury (56 vs 244, P < .001 vs control subjects), and increased release of creatine kinase (2695 vs 6974 U/L, P < .05 vs control subjects), aspartate aminotransferase (144 vs 229 U/L), and endothelin (1.02 vs 2.56 pg/mL, P < .001 vs control subjects). Conversely, the oxidant injury was markedly limited (conjugated dienes of 0.85 ± 0.09 Abs 240 nmol/L per 0.5 mL, P < .001 vs unmodified pump prime) with modification of cardiopulmonary bypass prime, resulting in increased cardiac output (5.1 ± 0.8 L/min), minimal dopamine need (P < .001 vs unmodified pump prime), no increase in pulmonary vascular resistance (44% ± 31%, P < .01 vs unmodified pump prime) or endothelin levels (0.64 ± 0.15 pg/mL, P < .001 vs unmodified pump prime), complete recovery of oxygenation (P < .01 vs unmodified pump prime), reduced neurologic damage (144 ± 33, P < .05 vs unmodified pump prime), and lower release of aspartate aminotransferase (124 ± 23 U/L, P < .05 vs unmodified pump prime) and creatine kinase (3366 ± 918, P < .05 vs unmodified pump prime).
Conclusions: A global reperfusion injury after deep hypothermic circulatory arrest was identified and changed. The injury is mediated by oxygen-derived free radicals, resulting in organ and endothelial dysfunction. Modification of global organ and endothelial damage is achieved by modifying the blood prime in the cardiopulmonary bypass circuit to deliver a controlled global reperfusate when reinstituting bypass.

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