Timing of steroid treatment is important for cerebral protection during cardiopulmonary bypass and circulatory arrest: Minimal protection of pump prime methylprednisolone

Objectives: The contact of cardiopulmonary bypass surface and patient's blood activates systemic inflammatory response which aggravates ischemia-reperfusion injury. This study evaluates the effects of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on cerebral protection using different steroid administration protocols. Methods: Eighteen (n=6/group) 4 week-old piglets were divided in three groups. Methylprednisolone (30 mg/kg) was administered intravenously 4 h prior to CPB in Group I, or added in pump prime in group II. Group III received no steroid. All animals were cooled to 15°C followed by 100 min of DHCA, then rewarmed over 40 min and sacrificed 6 h after CPB. Post-operative weight gain, bioelectrical impedance, colloid oncotic pressure (COP) and interleukin-6 (IL-6) were evaluated. Determination of cerebral trypan blue and immunohistochemical assays of transforming growth factor (TGF)-β₁ and caspase-3 activities were performed. Results: Post-operative % weight gain (13.0±3.8 (I) versus 26.4±9.9 (II) versus 22.6±6.4 (III), P=0.02); % bioimpedance reduction (14.5±8.0 (I) versus 38.3±13.3 (II) versus 30.5±8.0 (III), P=0.003); mean COP (mmHg) (14.9±1.8 (I) versus 10.9±2.0 (II) versus 6.5±1.8 (III), P=0.0001) and systemic IL-6 levels (pg/ml) (208.2±353.0 (I) versus 1562.1±1111.4 (II) versus 1712.3±533.2 (III), P=0.01) were significantly different between the groups. Spectrophotometric analysis of cerebral trypan blue (ng/g dry weight) was significantly different between the groups (0.0053±0.0010 (I) versus 0.0096±0.0026 (II) versus 0.0090±0.0019 (III), P=0.004). TGF-β₁ scores were 3.3±0.8 (I) versus 1.5±0.8 (II) versus 1.5±0.5 (III), P<0.05, groups I versus II and I versus III. Remarkable perivascular caspase-3 activity was observed in groups II and III. Conclusion: Different timing of steroid administration results in different inflammatory mediator response. Steroid in CPB prime is not significantly better than no steroid treatment, while systemic steroid pre-treatment significantly decreases systemic manifestation of inflammatory response and brain damage.