During the embryonic development of the heart and the greater vessels, some malformations may occur that can result in congenital heart diseases (CHD). The incidence of CHDs is estimated to be between 8 to 10 in 1000 live births. They can be the result of an underlying genetic disorder, be related to environmental factors or a combination of both.
CHDs may require corrective cardiac surgery in order to improve life expectancy. Due to clinical advances in the recent years, the survival rate of patients with congenital heart disease has improved significantly and it is estimated that by 2020 there will be 750,000 people with congenital heart disease.
Despite advances in cardiac surgery, the current techniques in protection of cyanotic myocardium during corrective cardiac surgery are not ideal. This is particularly relevant as these hearts sustain reoxygenation injury during cardiopulmonary bypass (CPB) using higher oxygen levels. We have hypothesised that cyanotic patients’ own oxygen levels during the corrective cardiac surgery could reduce myocardial and other organ injuries associated with reoxygenation insult.
In order to test our hypothesis we randomised 79 cyanotic patients to receive either normoxic or hyperoxic cardiopulmonary bypass during their corrective cardiac surgery. Systemic inflammatory responses and organ specific insults were assessed by measuring serum troponin I, alpha glutathione S-transferase (aGT), protein S100, 8- isoprostane, complement activation C3alpha, cortisol, interleukins 6, 8 and 10. The blood samples were taken at anaesthetic induction, 10 and 30 minutes after initiation of CPB, plus 10min, 4 hours and 24 hours post cessation of CPB.
We also performed a sub-analysis for cyanotic patients with double ventricular (n=47) and functional single ventricular pathology (n=32).
In all 79 patients, normoxic cardiopulmonary bypass significantly (p<0.05) reduced markers of organ damage (troponin I, aGT and protein S100), oxidative stress (8- isoprostane) and markers of inflammatory response (IL-6 and IL-8). In double b
ventricular patients, normoxic CPB resulted in lesser levels of aGT, protein S100, 8- isoprostane, IL-10markers and cortisol. Single-ventricle patients who were randomised to receive normoxic CPB, had a significantly decreased levels of troponin I, aGT, protein S100, 8-isoprostane, C3a, IL-6, IL-8 and cortisol.
Our results provided direct evidence of the beneficial effects of normoxic versus hyperoxic CPB on the heart, brain and liver as well as inflammatory and systemic stress response in cyanotic patients undergoing corrective cardiac surgery. These findings were more prominent in cyanotic patients with functional single ventricular pathology.
|Date of Award||23 Sep 2014|
- The University of Bristol
|Supervisor||Massimo Caputo (Supervisor)|