APAGBI/BJA/RCoA Research Grant
Novel strategies to protect the immature heart against reperfusion injury
Dr M Lewis
Background
Around 8 in every 1000 children born in the UK suffer from some form of congenital heart disease and in 2009/10 there were almost 3,600 paediatric open heart surgical procedures carried out in the UK. These diseases and subsequent surgical treatment are rare but significant for those who suffer from them, and outcomes are not universally good.
Recent work in Bristol has shown that the sequential addition of two commonly used drugs (isoproterenol and adenosine) prior to stopping blood flow through the heart, for instance in open heart surgery, provides extremely potent protection against subsequent damage to the adult heart upon reintroduction of blood (reperfusion). The mechanism underlying this "cardio-protection" involves consecutive activation of two different protein kinases (signalling proteins).
Aims
This novel and powerful cardio-protective intervention is currently being investigated in a variety of experimental models in adult rats in preparation for testing its efficacy in clinical practice for heart surgery. We now want to test the efficacy of this intervention in immature heart. Protecting the immature heart against ischaemia and reperfusion is important as paediatric hearts sustain significant reperfusion injury during open-heart surgery. We know that there are changes in protein signalling in the heart during development and therefore need to test whether our protection strategy is still effective in young hearts.
Methods
These proposed investigations will be performed in developing rat hearts. Hearts of young and adult rats will be extracted and used. An array of techniques (e.g. physiological, analytical, histological and molecular biological) will be used in this study.
Anticipated outcomes
We will discover whether this strategy is effective at protecting hearts undergoing stress due to lack of blood flow and oxygen.
Implications
This study will provide evidence that there is a mechanism in developing hearts which may be exploited to protect human hearts in children undergoing open heart surgery in whom blood flow is stopped. This will suggest further avenues to develop techniques to be used in clinical practice to reduce death and disability resulting from congenital heart disease.
Please see the NIAA's position statement on the use of animals in medical research.
