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J Thorac Cardiovasc Surg 2000;120:256-263
© 2000 The American Association for Thoracic Surgery

Surgery for congenital heart disease

Interleukin 6 induction in the canine myocardium after cardiopulmonary bypass

From the Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics,^a and the Section of Cardiovascular Sciences, Department of Medicine,^b Baylor College of Medicine, Houston, Tex.

This work was supported in part by grant HL-42550 from the National Institutes of Health and by grant 96G-1188 from the American Heart Association, Texas Affiliate.

Address for reprints: William J. Dreyer, MD, Pediatric Cardiology, MC 2-2280, Texas Children’s Hospital, 6621 Fannin, Houston, TX 77030 (E-mail: wdreyer{at}bcm.tmc.edu ).

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.
Conclusion: 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.

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