Antiinflammatory effects of colforsin daropate hydrochloride, a novel water-soluble forskolin derivative.
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.
Hayashida
N
N
Department of Surgery, Kurume University, Fukuoka, Japan. nobuhiko@med.kurume-u.ac.jp
Chihara
S
S
Tayama
E
E
Takaseya
T
T
Enomoto
N
N
Kawara
T
T
Aoyagi
S
S
D000368:Aged; D002315:Cardiopulmonary Bypass; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005576:Colforsin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D001026:Coronary Artery Bypass; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D011183:Postoperative Complications / Q000188:drug therapy* / Q000276:immunology; D011292:Premedication; D011446:Prospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000276:immunology; D014664:Vasodilation / Q000187:drug effects
D002316:Cardiotonic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D005576:Colforsin