Cytokine responses and anti-inflammatory strategies in Coronary Artery Bypass Grafting

Abstract

It is well established that conventional coronary artery bypass grafting with cardiopulmonary bypass induces a systemic inflammatory response, but the mechanism involved is still less understood. The present series of studies was designed to define the cytokine responses and its relationship to myocardial dysfunction. The anti-inflammatory effect of aprotinin, estrodial and adenosine were evaluated in low-risk male CABG patients.

The present studies confirmed that peripheral plasma levels of inflammatory cytokines IL-6, IL-8 and IL-10 are elevated after CABG with CPB, while off-pump CABG is accompanied with less cytokine responses and lesser myocardial injury. Further studies focus on stepwise analysis on the influence of different aspects associated with the CPB procedure are warranted. There was a trend towards higher peripheral cytokine levels in patients with impaired postoperative myocardial function.

Peripheral cytokine levels were correlated to postoperative myocardial injury. However, regional cytokine levels might be more important in the mechanism involved in myocardial dysfunction. Pump prime aprotinin fails to limits the systemic cytokine response after CABG. This could be due to a dose-dependent phenomenon. However, lower leukocyte counts and IL-10 release after reperfusion were found in the aprotinin group compared to the controls. The anti-inflammatory effect of pump prime aprotinin need further evaluation.

Pretreatment of two doses of 2 mg 17b-estradiol was proved to be safe for men during CABG in the present study. Leukocyte counts and plasma MPO levels were lower in patients with 17b-estradiol pretreatment, which indicate that estrogen limits leukocyte activation after CABG, but the present dose fails to limit systemic cytokine responses. A vasodilative effect of 17b-estradiol was observed after CABG, and this effect need further investigation. The present low dose adenosine pretreatment protocol (as compared to doses in the literature) reduces myocardial injury and improves cardiac function after CABG, but it failed in limiting systemic cytokine responses. However, four of the fifteen patients developed profound hypotension during the adenosine administration. This calls for further study to evaluate the safe protocol for adenosine pretreatment. A trend of lower systemic and myocardial neutrophil were observed in the adenosine patients, and further study is warranted to define whether adenosine may attenuate the neutrophil accumulation in myocardium after CABG.

It is well established that conventional coronary artery bypass grafting with cardiopulmonary bypass induces a systemic inflammatory response, but the mechanism involved is still less understood. The present series of studies was designed to define the cytokine responses and its relationship to myocardial dysfunction. The anti-inflammatory effect of aprotinin, estrodial and adenosine were evaluated in low-risk male CABG patients.

The present studies confirmed that peripheral plasma levels of inflammatory cytokines IL-6, IL-8 and IL-10 are elevated after CABG with CPB, while off-pump CABG is accompanied with less cytokine responses and lesser myocardial injury. Further studies focus on stepwise analysis on the influence of different aspects associated with the CPB procedure are warranted. There was a trend towards higher peripheral cytokine levels in patients with impaired postoperative myocardial function.

Peripheral cytokine levels were correlated to postoperative myocardial injury. However, regional cytokine levels might be more important in the mechanism involved in myocardial dysfunction. Pump prime aprotinin fails to limits the systemic cytokine response after CABG. This could be due to a dose-dependent phenomenon. However, lower leukocyte counts and IL-10 release after reperfusion were found in the aprotinin group compared to the controls. The anti-inflammatory effect of pump prime aprotinin need further evaluation.

Pretreatment of two doses of 2 mg 17b-estradiol was proved to be safe for men during CABG in the present study. Leukocyte counts and plasma MPO levels were lower in patients with 17b-estradiol pretreatment, which indicate that estrogen limits leukocyte activation after CABG, but the present dose fails to limit systemic cytokine responses. A vasodilative effect of 17b-estradiol was observed after CABG, and this effect need further investigation. The present low dose adenosine pretreatment protocol (as compared to doses in the literature) reduces myocardial injury and improves cardiac function after CABG, but it failed in limiting systemic cytokine responses. However, four of the fifteen patients developed profound hypotension during the adenosine administration. This calls for further study to evaluate the safe protocol for adenosine pretreatment. A trend of lower systemic and myocardial neutrophil were observed in the adenosine patients, and further study is warranted to define whether adenosine may attenuate the neutrophil accumulation in myocardium after CABG.