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A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Myocardial membrane injury in pediatric cardiac surgery: An animal model
Jonathan R Egan1, Tanya L Butler, Andrew D Cole
1Kids Heart Research, The Children's Hospital at Westmead, Sydney, Australia.
Insights
Pediatric cardiac surgery impairs heart function. Poloxamer 188 improved myocardial membrane protein expression, reduced capillary leak, and improved hemodynamics in a lamb model.
Area of Science:
- Cardiovascular Research
- Membrane Protein Biology
- Pediatric Cardiac Surgery
Background:
- Pediatric cardiac surgery often leads to reduced myocardial performance, potentially due to myocardial membrane protein alterations.
- The roles of dystrophin, dysferlin, and aquaporins in this context are not well understood.
- Poloxamer 188 is being investigated for its potential to mitigate membrane injury.
Purpose of the Study:
- To investigate changes in myocardial membrane proteins (dystrophin, dysferlin, aquaporins) following pediatric cardiac surgery.
- To evaluate the effect of poloxamer 188 on these proteins and cardiac function in a relevant animal model.
Main Methods:
- Eight lambs underwent cardiopulmonary bypass and aortic crossclamping, randomized to saline with or without poloxamer 188.
- Hearts were assessed for water content, capillary leak, and expression of dystrophin, dysferlin, and aquaporin 1 post-surgery.
- Hemodynamic parameters and colloid osmotic pressure were monitored.
Main Results:
- Ischemia/reperfusion reduced dysferlin expression and increased aquaporin 1, while dystrophin was unaffected.
- Poloxamer 188 treatment preserved dysferlin, normalized aquaporin 1, and maintained supranormal dystrophin levels.
- Poloxamer 188 reduced capillary leak, maintained colloid osmotic pressure, and improved hemodynamics (blood pressure, venous saturation, lactate).
Conclusions:
- Pediatric cardiac surgery induces significant changes in myocardial membrane protein expression.
- Poloxamer 188 demonstrated a protective effect, improving membrane protein profiles, reducing capillary leakage, and mitigating hemodynamic compromise.
- These findings suggest poloxamer 188 may be a beneficial therapeutic agent in pediatric cardiac surgery.
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.
