Myocardial membrane injury in pediatric cardiac surgery: An animal model

Jonathan R. Egan, Tanya L. Butler, Andrew D. Cole, Smartin Abraham, John S. Murala, David Baines, Neil Street, Lance Thompson, Oliver Biecker, John Dittmer, Sandra Cooper, Carol G. Au, Kathryn N. North, David S. Winlaw

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1154-1162
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume137
Issue number5
DOIs
StatePublished - May 1 2009

Fingerprint

Poloxamer
Thoracic Surgery
Animal Models
Pediatrics
Membranes
Wounds and Injuries
Dystrophin
Aquaporin 1
Hemodilution
Reperfusion
Membrane Proteins
Ischemia
Low Cardiac Output
Aquaporins
Proteins
Water
Osmotic Pressure
Colloids
Cardiopulmonary Bypass
Lactic Acid

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Myocardial membrane injury in pediatric cardiac surgery : An animal model. / Egan, Jonathan R.; Butler, Tanya L.; Cole, Andrew D.; Abraham, Smartin; Murala, John S.; Baines, David; Street, Neil; Thompson, Lance; Biecker, Oliver; Dittmer, John; Cooper, Sandra; Au, Carol G.; North, Kathryn N.; Winlaw, David S.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 137, No. 5, 01.05.2009, p. 1154-1162.

Research output: Contribution to journalArticle

Egan, JR, Butler, TL, Cole, AD, Abraham, S, Murala, JS, Baines, D, Street, N, Thompson, L, Biecker, O, Dittmer, J, Cooper, S, Au, CG, North, KN & Winlaw, DS 2009, 'Myocardial membrane injury in pediatric cardiac surgery: An animal model', Journal of Thoracic and Cardiovascular Surgery, vol. 137, no. 5, pp. 1154-1162. https://doi.org/10.1016/j.jtcvs.2008.10.009
Egan, Jonathan R. ; Butler, Tanya L. ; Cole, Andrew D. ; Abraham, Smartin ; Murala, John S. ; Baines, David ; Street, Neil ; Thompson, Lance ; Biecker, Oliver ; Dittmer, John ; Cooper, Sandra ; Au, Carol G. ; North, Kathryn N. ; Winlaw, David S. / Myocardial membrane injury in pediatric cardiac surgery : An animal model. In: Journal of Thoracic and Cardiovascular Surgery. 2009 ; Vol. 137, No. 5. pp. 1154-1162.
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AU - Egan, Jonathan R.

AU - Butler, Tanya L.

AU - Cole, Andrew D.

AU - Abraham, Smartin

AU - Murala, John S.

AU - Baines, David

AU - Street, Neil

AU - Thompson, Lance

AU - Biecker, Oliver

AU - Dittmer, John

AU - Cooper, Sandra

AU - Au, Carol G.

AU - North, Kathryn N.

AU - Winlaw, David S.

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N2 - 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.

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