Time course of early induction of intracellular adhesion molecule-1 messenger RNA during reperfusion, following cardiopulmonary bypass with hypothermic circulatory arrest in lambs.

OBJECTIVE

We investigated the time course of intracellular adhesion molecule-1 messenger RNA induction following cardiopulmonary bypass with hypothermic circulatory arrest.

DESIGN

Animal case study.

SETTING

An animal research laboratory and molecular biology laboratory at a university children's hospital.

SUBJECTS

Neonatal lambs.

INTERVENTIONS

Neonatal lambs were cooled on cardiopulmonary bypass for 30 mins, followed by hypothermic circulatory arrest at 15 degrees C for 120 mins and warming on cardiopulmonary bypass for 30 mins. Animals were killed after 0, 3, or 6 hrs of reperfusion. Control animals had sternotomy only. To generate a species-specific probe, ovine intracellular adhesion molecule-1 complementary DNA was cloned and sequenced. By using a ribonuclease protection assay, we measured intracellular adhesion molecule-1 messenger RNA in lung, cardiac ventricle, and brain, with nonmuscle actin as an internal control. Data were quantitated by Phosphorlmager.

MEASUREMENTS AND MAIN RESULTS

In lung, intracellular adhesion molecule-1 messenger RNA was induced immediately following cardiopulmonary bypass/hypothermic circulatory arrest with no reperfusion (mean increase of 1.7-fold vs. control). The highest intracellular adhesion molecule-1 messenger RNA levels were found at 3 hrs reperfusion (mean increase of 2.8-fold vs. control), but the levels remained significantly elevated at 6 hrs reperfusion (mean increase of two-fold vs. control). Although not statistically significant, cardiac ventricle showed the highest intracellular adhesion molecule-1 messenger RNA levels at 6 hrs reperfusion. The brain had lower levels of intracellular adhesion molecule-1 messenger RNA than lung or ventricle and did not demonstrate induction.

CONCLUSIONS

We found an earlier peak induction of intracellular adhesion molecule-1 messenger RNA in lung compared with ventricle. This may represent both local ischemic injury and filtering of bypass-related inflammatory mediators in the pulmonary capillary bed. Early intracellular adhesion molecule-1 messenger RNA induction may reflect its role in neutrophil-mediated, ischemia-reperfusion injury.