Minocycline and Pulsatile Blood Flow as a Protective Approach in Cardiopulmonary Bypass-Induced Lung Injuries

Objectives: Children with congenital heart diseases often need corrective surgery using a cardiopulmonary bypass (CPB). Although the application of CPB has become indispensable, negative side effects such as pulmonary dysfunction or acute respiratory distress syndrome can appear. The aim of our study was to evaluate possible lung injuries after CPB and to assess whether different flow modalities (pulsatile vs. non-pulsatile flow) or application of the antibiotic minocycline might be of advantage.

Methods: Therefore, we analyzed five experimental groups of piglets (angler-saddle-pig, 4 weeks old, 8–15 kg): control group, control group + minocycline, CPB (non-pulsatile flow), CPB (pulsatile flow), CPB + minocycline. The CPB was performed for 90 minutes, including 60 minutes of aortic cross clamping and 30 minutes of reperfusion, followed by 120 minutes of recovery without CPB. Minocycline was applied before CPB (4mg/kg) and after CPB (2 mg/kg). The piglets were euthanized after surgery and lung biopsies were analyzed histologically. Moreover ATP-content was measured.

Results: We found that CPB induced lung edema, inflammation, oxidative and nitrosative stress and caspase-dependent and -independent apoptosis. Furthermore, CPB led to ATP-depletion. Minocycline + pulsatile flow were able to significantly attenuate inflammation, oxidative and nitrosative stress and PAR-dependent cell death. Moreover, minocycline as well as pulsation prevented from cellular ATP depletion.

Conclusion: CPB induced lung injuries, which were attenuated by a pulsatile blood flow and minocycline.