Antiinflammatory effects of colforsin daropate hydrochloride, a novel water-soluble forskolin derivative.

ABSTRACT

BACKGROUND: To evaluate the effects of colforsin daropate hydrochloride (colforsin), a water-soluble forskolin derivative, on hemodynamics and systemic inflammatory response after cardiopulmonary bypass, we conducted a prospective randomized study. METHODS: Twenty-nine patients undergoing coronary artery bypass grafting were randomized to receive either colforsin treatment (colforsin; n = 14) or no colforsin treatment (control; n = 15). Administration of colforsin (0.5 microg.kg(-1).min(-1)) was started after induction of anesthesia and was continued for 6 hours. Perioperative cytokine and cyclic adenosine monophosphate levels, hemodynamics, and respiratory function were measured serially. RESULTS: Marked positive inotropic and vasodilatory effects were observed in patients receiving colforsin. Interleukin 1beta, interleukin 6, and interleukin 8 levels after cardiopulmonary bypass were significantly (p < 0.05) lower in the colforsin group. Plasma levels of cyclic adenosine monophosphate increased significantly (p < 0.05) in the colforsin group, and the levels correlated inversely (r = -0.56, p = 0.002) with the respiratory index after cardiopulmonary bypass. CONCLUSIONS: Intraoperative administration of colforsin daropate hydrochloride had potent inotropic and vasodilatory activity and attenuated cytokine production and respiratory dysfunction after cardiopulmonary bypass. The results indicate that the technique can be a novel therapeutic strategy for the systemic inflammatory response associated with cardiopulmonary bypass.