Inhibitory effect of milrinone on cytokine production after cardiopulmonary bypass

It has been suggested that cyclic adenosine monophosphate-elevating agents suppress cytokine production. To evaluate the effects of milrinone, a phosphodiesterase III inhibitor, on cytokine production after cardiopulmonary bypass, we conducted a prospective randomized study.

Twenty-four patients undergoing coronary artery bypass grafting were randomized to receive either milrinone treatment (milrinone, n = 12) or no milrinone treatment (control, n = 12). Administration of milrinone (0.5 microg x kg(-1) x min(-1)) was started after induction of anesthesia and was continued for 24 hours. Blood samples for determination of plasma cyclic adenosine monophosphate, tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8 levels were collected perioperatively.

No significant differences were observed in tumor necrosis factor-alpha and interleukin-8 levels between the groups. Interleukin-1beta and interleukin-6 levels after cardiopulmonary bypass were significantly (p < 0.05) lower in the milrinone group than in the control group. Plasma levels of cyclic adenosine monophosphate increased significantly (p < 0.05) after the administration of milrinone and the levels correlated inversely (r = -0.55, p < 0.01) with interleukin-6 levels.

The results indicate that milrinone suppresses cytokine production by elevating cyclic adenosine monophosphate levels in patients undergoing cardiopulmonary bypass. With its positive inotropic and vasodilator activities, milrinone may have antiinflammatory effects.