Jenny Vedin

Activation of complement and leukocyte receptors during on- and off pump coronary artery bypass surgery

OBJECTIVE The aim of this prospective, randomised study was to investigate the influence of extracorporeal circulation on the inflammatory response, our hypothesis being that off pump coronary artery bypass grafting (OFFCAB) procedures would generate less activation than on pump procedures (ONCAB). METHODS Patients admitted for elective CABG were randomised to either ONCAB or OFFCAB surgery and blood samples were taken during and up to 24 h after the operation. We measured complement factors C5a and the terminal complement complex (TCC, C59-b), and the interleukins IL-6 and IL-8. Leukocytes were studied for cellular counts and adhesion molecules (CD11b, CD35 and CD62L) by flow cytometry. We included a combination of activity markers with different aspects of neutrophil function and combined these with in vitro activation. RESULTS The complement factors C5a and TCC showed a more rapid (P=0.02, P<0.001) and TCC a more profound (P<0.001) increase in the ONCAB group than in the OFFCAB group during the operation, after that there were no inter-group differences. Cellular markers, cell counts and interleukin levels were activated by surgery but with no difference between groups. CONCLUSION This prospective, randomised study showed less complement activation in low risk OFFCAB, compared to ONCAB patients.

Peripheral blood monocyte activation during coronary artery bypass grafting with or without cardiopulmonary bypass

Objective. The aim of this prospective, randomized study was to investigate the impact of coronary artery bypass grafting (CABG) on peripheral monocytes and to evaluate the additional effect of cardiopulmonary bypass (CPB). Design. Twenty patients admitted for elective CABG were randomized to either on-pump (ONCAB, n=9) or off-pump (OFFCAB, n=11) surgery and blood samples were drawn before, during and 24 h after the operation. The total number of monocytes and the proportion of the more mature CD16+/CD14+ monocytes were measured. Expression of activation markers (CD11b, CD35 and CD62L) and oxidative burst were determined using flow cytometry on both resting and in vitro stimulated cells. Serum concentrations of soluble CD14 and monocytes/macrophage chemotactic protein 1 (MCP-1) were analysed. Results. During surgery there was a selective decrease in the proportion of CD16+/CD14+ monocytes compared to total monocytes. These had returned to preoperative values 24 h after surgery while the total number of monocytes had increased more than 100%. Intracellular production of oxygen free radical H2O2 was increased in the ONCAB group during surgery compared to OFFCAB. Monocyte expression and in vitro mobilization of complement receptors, CD11b and CD35, were similar in both study groups during and after surgery as was the expression of CD62L. Serum levels of MCP-1 decreased during surgery as did soluble CD14, both with increased levels again the day after surgery. Conclusion. It is concluded that the circulating monocyte population is activated during and as a consequence of CABG. There were few apparent additional effects of CPB found in this study. In this setting the inflammation caused by the surgery procedure per se probably surpasses the impact of the CPB on circulating blood monocytes.

Cardiovascular function during the first 24 hours after off pump coronary artery bypass grafting–a prospective, randomized study

We hypothesized that cardiovascular performance during the first 24 postoperative hours would be better in patients after off pump coronary artery bypass grafting compared to conventional on pump surgery. Fifty-nine patients were randomized to on or off pump coronary artery bypass grafting. Hemodynamic parameters, including cardiac index and systemic vascular resistance index were measured before and at 1, 4, and 20 h after surgery. Troponin T and creatine kinase-MB (CK-MB) were measured before and at 1, 6, and 20 h after surgery. There was no difference in age, sex, ejection fraction or number of grafts between groups. Cardiac index was higher (p=0.05) and systemic vascular resistance index was lower (p=0.007) in the off pump group 1 h after arrival in the intensive care unit. CK-MB and troponin T were significantly lower in the off pump group after 1 h (CK-MB p<0.001, troponin T p<0.001) and after 6 h (CK-MB p=0.02, troponin T p<0.001). After 24 h there was no difference between the two groups. In conclusion, immediately after surgery there was better cardiovascular performance and less release of markers of myocardial damage after off pump coronary surgery. After 24 h all differences were eliminated.

Preoperative unstable angina causes venous adaptation to surgical graft injury.

AbstractIschemic preconditioning may provide a systemic organ protection, evident as the phenomenon known as remote preconditioning. Unstable angina may be a clinical analogue to ischemic preconditioning. Vein graft harvesting induces inflammation of the graft wall. We hypothesized that preoperative unstable angina preconditions vein grafts and reduces the inflammatory response to graft harvesting.Consecutive patients with stable or unstable angina undergoing open heart surgery (n = 12 in each group) were studied. Saphenous vein biopsies were collected at the start of graft harvesting, and when the last proximal anastomosis to the aorta was finished (average 112 minutes later). Gene expression of inflammatory mediators (tumor necrosis factor alpha, interleukin-1β (IL-1β), E-selectin (CD62E), intercellular leukocyte adhesion molecule 1, inducible nitric oxide synthase, endothelin-1) increased after surgical handling (semiquantitative RT-PCR). In vein grafts from unstable patients the increase was attenuated for Il-1β (p < 0.004) and CD62E (p < 0.001). In stable patients the protein expression of IκBα and heat shock protein72 was reduced by surgical handling (p < 0.04), but was not influenced in unstable patients (immunoblotting). In vitro relaxation to acetylcholine was enhanced, and contractions to phenylephrine and endothelin-1 were attenuated in veins rings from unstable patients (p < 0.003).In conclusion, surgical handling of vein grafts induces inflammation of the vessel wall. This response was reduced in grafts from patients with unstable angina, indicating a possible systemic preconditioning-like effect of acute coronary syndromes.

Constrictive pericarditis with constrictive epicarditis.

A 63 year old male was referred because of heart failure. He had received combined radiotherapy and chemotherapy for a thymic carcinoma seven years earlier and was considered in remission. He was severely symptomatic, mainly from right heart failure, with leg oedema and with large amounts of ascites, requiring frequent laparocenteses. He had been treated with steroids and high doses of diuretics orally and intravenously for several months with limited clinical response. A preoperative computed tomography of the chest showed a thickened pericardium without calcifications and there were no signs of recurrent tumour (Figure 1a, 1b). A chest X-ray was not conclusive (Figure 2). Constrictive pericarditis was diagnosed by left and right heart catheterization and by Doppler echocardiography with Tissue Velocity Imaging techniques. He underwent pericardectomy via a median sternotomy. The pericardium was fibrotic and thickened (5 mm) and adherent to the heart except in a small anterior area. The thymus was enlarged and fibrotic and was clinically suspicious for malignancy, but a frozen section was without evidence of recurrent cancer. The pericardium was dissected away from the heart (from phrenic to phrenic) en bloc with the thymus. Following this, there was some hemodynamic improvement (the central venous pressure decreased from 30 mm of mercury to 24 mm). The heart was, however, still engaged in a thick, white, fibrous epicardial tissue which seemed to prevent adequate filling of the heart. Removal of the epicardial peel was attempted but abandoned for fear of severe myocardial injury. Instead we choose to perform a number of transverse and longitudinal incisions in the epicardium allowing the heart to successively dilate and fill, and the central venous pressures decreased further (Figure 3). This method was originally described by Heimbecker in 1983 and was than called ‘‘the Waffle procedure’’. It has later been presented as ‘‘the Turtle Cage Operation’’. Our patient made a fast recovery and was asymptomatic with a low dose of diuretics at follow-up. As the final histopathologic examination of the specimen showed remaining viable malignancy, he will, however, need further chemotherapy.