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J Thorac Cardiovasc Surg 2009;137:1154-1162
© 2009 The American Association for Thoracic Surgery

Congenital Heart Disease

Myocardial membrane injury in pediatric cardiac surgery: An animal model

^a Kids Heart Research, The Children's Hospital at Westmead, Sydney, Australia
^b Discipline of Pediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, Australia
^c Institute for Neuromuscular Research, The Children's Hospital at Westmead, Sydney, Australia

Received for publication June 19, 2008; revisions received September 1, 2008; accepted for publication October 9, 2008.

^_* Address for reprints: A/Prof David S. Winlaw, Paediatric Cardiac Surgeon, Head, Kids Heart Research, Locked Bag 4001, Westmead NSW 2145, Australia. (Email: davidw{at}chw.edu.au).

Objective: Reduced myocardial performance invariably follows pediatric cardiac surgery and is manifested by a low cardiac output state in its severest form. The role of myocardial membrane proteins in this setting is unknown. Dystrophin and dysferlin are involved in membrane integrity, whereas aquaporins selectively transport water. These proteins were examined in a model of pediatric cardiac surgery, together with a trial of poloxamer 188, which may reduce membrane injury.

Methods: Eight lambs were randomized to saline with or without poloxamer 188. Lambs underwent 2 hours of cardiopulmonary bypass and aortic crossclamping. After a further 9 hours of monitoring, the hearts were assessed for water content, capillary leak, and protein expression.

Results: Dystrophin expression was unaffected by ischemia/reperfusion, but dysferlin expression was reduced. Aquaporin 1 protein increased after ischemia/reperfusion. Poloxamer 188 administration was associated with supranormal levels of dystrophin, preservation of dysferlin expression, and normalization of aquaporin 1 expression. Poloxamer 188 was associated with less capillary leak, maintained colloid osmotic pressure, and less hemodilution. Poloxamer 188 was associated with an improved hemodynamic profile (higher blood pressure, higher venous saturation, and lower lactate), although the heart rate tended to be higher.

Conclusions: Changes in protein expression within the myocardial membrane were found in a clinically relevant model of pediatric cardiac surgery. Indicators of reduced performance, such as lower blood pressure and lower oxygen delivery, were lessened in association with the administration of the membrane protecting poloxamer 188. Poloxamer 188 was also associated with potentially beneficial changes in membrane protein expression, reduced capillary leakage, and less hemodilution.