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.


METHODS
Animal case study.


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


METHODS
Neonatal lambs.


METHODS
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.


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.
Tabbutt
Sarah
S
Department of Cardiology, Children's Hospital, Dana Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA.
Newburger
Jane W
JW
Hickey
Paul R
PR
Mayer
John E
JE
Neufeld
Ellis J
EJ
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D002315:Cardiopulmonary Bypass; D006352:Heart Ventricles / Q000378:metabolism; D007036:Hypothermia, Induced; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D015427:Reperfusion Injury / Q000503:physiopathology; D012756:Sheep
D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1