Different organ injury mechanisms following cardiopulmonary bypass and circulatory arrest in a paediatric model

  • Dr Jonathan McGuinness, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland., Ireland
  • Dr Niamh Keenan, Department of Surgical Research, Royal College of Surgeons in Ireland, Dublin, Ireland., Ireland
  • Dr Darren McLoughlin, Department of Surgical Research, Royal College of Surgeons in Ireland, Dublin, Ireland., Ireland
  • Mr Omar Al-Awadi, iRoyal College of Surgeons, Ireland
  • Dr John Byrne, Department of Surgical Research, Royal College of Surgeons in Ireland, Dublin, Ireland., Ireland
  • Mr Colin Canavan, Department of Surgical Research, Royal College of Surgeons in Ireland, Dublin, Ireland., Ireland
  • Prof David Bouchier-Hayes, Department of Surgical Research, Royal College of Surgeons in Ireland, Dublin, Ireland., Ireland
  • Prof J Redmond, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland., Ireland

    • Introduction: Multiple organ dysfunction(MOD) following cardiopulmonary bypass(CPB) and circulatory arrest for repair of complex congenital cardiac defects causes major morbidity. The exact mechanism and timing of injury is unclear.

    Methods: Using a juvenile porcine CPB and circulatory arrest model, we monitored the development of MOD in the first 24hrs post-operatively. Five experiments were completed at 8hrs, and 5 at 24hrs. All results are reported as mean+/-standard error of mean, all p<0.05 on ANOVA.

    Results: A low cardiac output state developed in all cases at 10-12hrs. Cardiac injury manifested as a troponin peak at 6hrs(baseline:0.224+/-0.1ng/ml; 6hrs:44.36+/-8.67ng/ml), and diastolic dysfunction at 4-10hrs. Pulmonary injury was demonstrated by a reduction in dynamic lung compliance at 10hrs(baseline:10.12+/-0.124ml/cmH2O; 10hrs:5.7+/-0.29ml/cmH2O), followed by a drop in PO2 at 12hrs(baseline:49.54+/-3.02kPa; 12hrs:35.72+/-7.19kPa), and a reduction in the PO2/FiO2 ratio into ARDS range. These changes were preceded by peaks of IL-6 at 4hrs(baseline:0+/-0pg/ml; 4hrs:314.07+/-93.47pg/ml), and WCC at 6hrs(baseline:17.07+/-4x109/L; 6hrs:25.25+/-7.13x109/L); with marked pulmonary neutrophil infiltration and oedema at 8hrs.
    Renal injury presented as progressive tubular structural damage from 2-12hrs(urinary N-acetyl-glucosaminidase: 2hrs:+/-0.27U/l; 12hrs:2+/-0.31U/l), and subsequent impairment of tubular function at 4hrs with some recovery at 24hrs(fractional excretion of urinary sodium: baseline:0.76+/-0.22; 4hrs:0.32+/-0.11; 16hrs:0.04+/-0.01; 24hrs:0.2+/-0.1). Throughout this period, renal NIRS readings were >65%.

    Conclusions: Post-operative pulmonary dysfunction appears related to the systemic inflammatory response, while renal medullary injury begins before its onset and begins to resolve despite a low cardiac output state, suggesting an intra-operative ischemic insult.