Induction of inflammatory mediators during reperfusion of the human heart

Background. Cardioplegia and reperfusion may induce an inflammatory reactio n, which may contribute to postoperative morbidity and mortality. Methods. Gene expression of cytokines, adhesion molecules, and vasoactive s ubstances was evaluated in left ventricular biopsies taken before cardiople gia (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 amp lified with a semiquantitative reverse transcription polymerase chain react ion. Results. Cardioplegia-reperfusion increased mRNA for E-selectin by a factor of 17 +/- 5 (p < 0.002) (mean +/- SEM), interleukin-la with 9 +/- 3 (p < 0 .007), tumor necrosis factor-alpha with 6 +/- 3 (p < 0.05), interleukin-2 r eceptor <alpha> chain CD25 with 2 +/- 0.6 (p < 0.04), and intercellular adh esion molecule-1 with 2 +/- 0.4 (p < 0.005). Before cardioplegia, mRNA for endothelial nitric oxide synthase was predominantly detected in unstable an gina patients, and increased by a factor of 11 +/- 6 (p < 0.02) during repe rfusion. 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 transcrip tion factor nuclear factor kappa B (NF kappaB), 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 hum an heart, which is more pronounced in patients with unstable angina. It inv olves NF<kappa>B activation and expression of several NF kappaB-regulated g enes. (Ann Thorac Surg 2001;71:226-32) (C) 2001 by The Society of Thoracic Surgeons.