Effect of cardiopulmonary bypass on a stress response pathway in a recovery rat's model

Abstract

The systemic inflammation response syndrome (SIRS) is a common side-effect of the cardiopulmonary bypass (CPB) in cardiac surgery. SIRS can trigger multiple organ dysfunction which can lead to patient death. Pulmonary dysfunction is the most common post-operative complication of CPB. However, the lack of animal models recapitulating the disease prevents the investigation of pathophysiological mechanisms of CPB's complications. This project aims to develop a robust rat model recapitulating the SIRS during an extracorporeal circulation. This model mimics the clinical procedure and will be used to investigate the activation of stress response pathway (ISR). Surgery was made under isoflurane (3%, 02: 0.4L/min) and CPB was performed under propofol infusion (5μg/kg/hr) on mechanically ventilated 12 weeks old rats. Blood was drawn from cava vein then reinjected in the aorta. Hemodynamic parameters were measured in femoral artery. The circuit was primed with Ringer Lactate (< 1/3 of rats’ volemia). To oxygenate the blood, an oxygenator was in line with the peristaltic pump. Hemodynamic and blood gases were monitored during the procedure. After 30 mins of CPB, rats were culled. Blood and organs were collected for ISR pathway analyses. Mean blood pressure was maintained at 50mmHg with a PaO2 > 380mmHg. Lactate and kaliemia were increased after CPB (pre: 1.31 ± 0.49 vs post: 5.32 ± 3.67 and pre: 4.73 ± 0.15 vs post: 6.83 ± 2.22, respectively, N = 3). An activation of the ISR pathway was demonstrated by western blot on lung from CPB rats compared to Sham rats, with a 10-fold increase in p(ser51)-eIF2α/eIF2α ratio, a 2-fold increase in CHOP and GADD34 protein levels. We have developed a pre-clinical rat model of CPB in which preliminary data highlight an early activation of ISR pathway in lung. This model will be used to decipher the pathophysiological mechanisms of CPB's complications.