Induction of inflammatory mediators during reperfusion of the human heart.
BACKGROUND
Cardioplegia and reperfusion may induce an inflammatory reaction, which may contribute to postoperative morbidity and mortality.


METHODS
Gene expression of cytokines, adhesion molecules, and vasoactive substances was evaluated in left ventricular biopsies taken before cardioplegia (lasting approximately 70 minutes) and after reperfusion (approximately 40 minutes) from 19 patients (5 with valvular or combined disease, 7 with stable angina pectoris, 7 with unstable angina). mRNA was extracted and amplified with a semiquantitative reverse transcription polymerase chain reaction.


RESULTS
Cardioplegia-reperfusion increased mRNA for E-selectin by a factor of 17 +/- 5 (p < 0.002) (mean +/- SEM), interleukin-1beta, with 9 +/- 3 (p < 0.007), tumor necrosis factor-alpha with 6 +/- 3 (p < 0.05), interleukin-2 receptor alpha chain CD25 with 2 +/- 0.6 (p < 0.04), and intercellular adhesion molecule-1 with 2 +/- 0.4 (p < 0.005). Before cardioplegia, mRNA for endothelial nitric oxide synthase was predominantly detected in unstable angina patients, and increased by a factor of 11 +/- 6 (p < 0.02) during reperfusion. mRNA for endothelin-1 decreased by a factor of 0.5 +/- 0.1 (p < 0.0005). The changes were more pronounced in unstable patients. The transcription factor nuclear factor kappa B (NFkappaB), which regulates expression of inflammatory mediators, was activated during reperfusion (n = 10, p < 0.0001).


CONCLUSIONS
Open heart surgery induces an inflammatory response in the human heart, which is more pronounced in patients with unstable angina. It involves NFkappaB activation and expression of several NFkappaB-regulated genes.
Valen
G
G
Department of Thoracic Surgery, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden. guro.valen@cmm.ki.se
Paulsson
G
G
Vaage
J
J
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000378:metabolism; D000789:Angina, Unstable / Q000378:metabolism; D004586:Electrophoresis; D005260:Female; D015870:Gene Expression; D006324:Heart Arrest, Induced; D006331:Heart Diseases / Q000378:metabolism*; D006349:Heart Valve Diseases / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B; D015854:Up-Regulation
D018836:Inflammation Mediators; D016328:NF-kappa B