Interleukin 6 induction in the canine myocardium after cardiopulmonary bypass.
OBJECTIVE
Interleukin 6 is a proinflammatory cytokine with a plasma concentration that has been noted to increase in response to cardiopulmonary bypass. The source of interleukin 6 after cardiopulmonary bypass is unknown. This study examined the myocardium as a potential source of interleukin 6 in this context.


METHODS
Dogs underwent 90 minutes of hypothermic cardiopulmonary bypass with 60 minutes of cardioplegic arrest. After rewarming, they were reperfused with the chest open for either 3 (n = 4) or 6 (n = 4) hours, at the end of which myocardial samples were obtained. Four additional animals undergoing open thoracotomy without bypass served as time-matched controls. Northern blot analysis, reverse transcriptase-polymerase chain reaction, and in situ hybridization were used to examine the myocardium for the induction of interleukin 6 and intercellular adhesion molecule-1.


RESULTS
Northern blot analysis and reverse transcriptase-polymerase chain reaction demonstrated a marked increase in myocardial interleukin 6 messenger RNA in 3 of 4 dogs at 3 hours after bypass and 3 of 4 dogs at 6 hours after bypass, which was not present in sham-bypass control animals. Northern blots at 3 hours after cardiopulmonary bypass also demonstrated myocardial intercellular adhesion molecule-1 induction. In situ hybridization studies confirmed that cardiac myocytes were a principal source of interleukin 6 messenger RNA early after cardiopulmonary bypass. Northern blots of messenger RNA extracted from isolated neutrophils and mononuclear leukocytes obtained from blood samples before bypass, at the end of bypass, and 3 hours after bypass failed to demonstrate interleukin 6 induction.


CONCLUSIONS
Despite protection with cold cardioplegic arrest, the myocardium was a significant source of interleukin 6 synthesis after cardiopulmonary bypass. Local production of interleukin 6 may play a pivotal role in postoperative myocardial function.
Dreyer
W J
WJ
Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, and the Section of Cardiovascular Sciences, Baylor College of Medicine, Houston, TX, USA. wdreyer@bcm.tmc.edu
Phillips
S C
SC
Lindsey
M L
ML
Jackson
P
P
Bowles
N E
NE
Michael
L H
LH
Entman
M L
ML
D000818:Animals; D015152:Blotting, Northern; D002314:Cardioplegic Solutions; D002315:Cardiopulmonary Bypass; D004285:Dogs; D006324:Heart Arrest, Induced; D017403:In Situ Hybridization; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002314:Cardioplegic Solutions; D018836:Inflammation Mediators; D015850:Interleukin-6; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1