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To determine whether angiogenic growth factor levels are altered during and after cardiac surgery, plasma concentrations of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and transforming growth factor beta1 (TGFbeta1) were measured in 32 patients undergoing coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC). EGF levels significantly decreased during ECC and remained low until the 24th post-operative hour with no difference between complicated and uncomplicated patients. TGFbeta1 and bFGF concentrations significantly increased at the end of ECC and after cross-clamp release, and returned to pre-operative values at the 6th post-operative hour suggesting that the source of these elevations are the lungs and heart. After cross-clamp release bFGF levels but not TGFbeta1 ones were higher in patients with respiratory impairments. VEGF values increased significantly at the 6th and 24th post-operative hours. At the 24th post-operative hour plasma VEGF levels were higher in patients with cardiovascular and hematological impairments. In conclusion, these results highlight that the angiogenic network is profoundly altered in patients undergoing cardiopulmonary bypass as previously demonstrated for lipidic, cytokine and haematopoietic growth factor ones and identify an association between specific post-CABG complications and systemic release of bFGF and VEGF.

To determine whether colony-stimulating factor (CSF) might participate to the inflammatory response after cardiac surgery, plasma concentrations of granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF) and GM-CSF were measured in 31 patients undergoing coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC). Plasma G-CSF and M-CSF concentrations increased after weaning of ECC, reached maximum value at the sixth post-operative hour, and remained elevated at the 24th post-operative hour. In contrast, plasma GM-CSF levels did not change. Plasma M-CSF, G-CSF and GM-CSF values were not different whether patients developed post-operative complications or not. In conclusion, M-CSF and G-CSF are produced after CABG surgery despite the use of high aprotinin doses in hope to abrogate the inflammatory response. G-CSF and M-CSF might play a role in the inflammatory process often observed after CABG surgery.

Bone marrow stromal cells regulate marrow haematopoiesis by secreting interleukins (IL) such as IL-8. Lipid mediators modulate IL-8 synthesis in numerous cell types. We have investigated the effects of 5 lipid mediators (PAF, PGE(2), LTB(4), 12-HETE and 15-HETE) on the spontaneous and cytokine-induced IL-8 synthesis by human bone marrow stromal cells. By using reverse-transcriptase polymerase chain reaction (RT-PCR) we demonstrate that these cells constitutively express IL-8 transcripts. By using a specific ELISA, we found that the production of IL-8 by marrow stromal cells is enhanced after stimulation with 12-HETE (1 microM) both in serum-free and serum-containing culture medium. LTB(4)(1 microM) enhances IL-8 production only in serum-supplemented medium. PAF, PGE(2)and 15-HETE (1 microM to 0.1 nM) have no effect on the spontaneous and serum-induced production of IL-8 by human bone marrow stromal cells. PGE(2)(1 microM or 10 nM) reduces marrow stromal cell IL-8 synthesis in response to IL-1alpha or TNF-alpha. In contrast, PAF, 12-HETE, 15-HETE and LTB(4)have no effect. In conclusion, various lipid mediators modulate the spontaneous, serum- or cytokine-induced IL-8 synthesis by bone marrow stromal cells, highlighting, for the first time, their potential role in the regulation of IL-8 production within the human bone marrow., (Copyright 1999 Academic Press.)

In this study the authors assessed the sequential release of lipid mediators (TXB2, PGE2, 6-keto-PGF1alpha, LTB4, LTC4, PAF), pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha) and anti-inflammatory cytokines (IL-4, IL-10) in 17 patients undergoing coronary artery bypass graft (CABG) with extracorporeal circulation (ECC). Time course of appearance of inflammatory mediators revealed the early and transient increase in lipid mediator plasma concentrations (6-keto-PGF1alpha, LTB4, LTC4, PAF) whereas cytokines (IL-6, IL-8, IL-10) were involved only in late pre- and post-operative periods. No variation of TXB2, PGE2, IL-4 and TNF-alpha levels were found. No correlation was documented between the levels of lipid mediators and pro- or anti-inflammatory cytokines suggesting that lipidic compounds are not implicated in the genesis of cytokines which appear much later involved. Despite the common use of high doses of aprotinin (a non-specific enzyme inhibitor) in hope to abrogate the inflammatory response to cardiopulmonary bypass procedure, this study reports the persistent release of several inflammatory compounds that might be involved in the post-CABG multiple organ failure syndromes., (Copyright 1999 Academic Press.)

In this study the authors assessed plasma leukaemia inhibitory factor (LIF), interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6R) concentrations in 28 patients undergoing coronary artery bypass graft (CABG) with extracorporeal circulation (ECC). Plasma IL-6 levels increased during ECC, reaching a 33-fold increase 6 h after surgery as compared to pre-operative values. In contrast, plasma sIL-6R and LIF concentrations did not vary significantly during cardiac surgery. Thus, LIF is not implicated in the haematological changes and in the inflammatory syndrome observed after CABG. Despite the fact that LIF and IL-6 exhibit several common biological activities, the production of these two cytokines is differently regulated during cardiac surgery with ECC. Plasma IL-6 levels increased during cardiac surgery while sIL-6R levels did not changed. These data contrast with the decreased sIL-6R concentrations with concomitantly high IL-6 levels in patients with sepsis syndrome suggesting that inflammatory reactions in sepsis and after cardiopulmonary bypass are triggered by different mechanisms.