Antioxidant therapy with Salvia miltiorrhiza decreases plasma endothelin-1 and thromboxane B2 after cardiopulmonary bypass in patients with congenital heart disease.
OBJECTIVE
The endothelium-derived vasoconstrictor endothelin-1 is increased after cardiopulmonary bypass in children with congenital heart defects. This study determines whether antioxidant therapy with Salvia miltiorrhiza injection, an herb extract containing phenolic compounds, prevents the postoperative increase of endothelin-1. The relationship between endothelin-1 and the endothelium-derived prostacyclin (prostaglandin I2) and thromboxane A2 postoperatively is also investigated.


METHODS
Twenty children with congenital heart defects and pulmonary hypertension were randomly assigned to group A (placebo control, n=10) or B (200 mg/kg Salvia miltiorrhiza intravenously after anesthesia induction and at the time of rewarming, respectively; n =10) before cardiac surgery. Central venous blood samples were taken before operation (T(0)), 10 (T(1)) and 30 minutes (T(2)) after starting cardiopulmonary bypass, 10 (T(3)) and 30 minutes (T(4)) after aortic declamping, and 30 minutes (T(5)) and 24 hours (T(6)) after termination of cardiopulmonary bypass. Plasma lipid peroxidation product malondialdehyde, myocardial specific creatine kinase-MB activity, thromboxane B2, and 6-keto-prostaglandin F(1 alpha) (stable metabolites of thromboxane A2 and prostaglandin I2) were measured.


RESULTS
Malondialdehyde increased significantly at T(1) in group A and remained significantly higher than in group B thereafter (P <.05). Malondialdehyde in group B did not significantly increase over time. At T(5), plasma creatine kinase-MB, thromboxane B2, and endothelin-1 in group B were lower than in group A (P <.05); malondialdehyde correlated significantly with creatine kinase-MB (r = 0.71, P =.0005). At T(6), endothelin-1 negatively correlated with the 6-keto-prostaglandin F(1 alpha)/thromboxane B2 ratio (r = -0.64, P =.0025).


CONCLUSIONS
Antioxidant therapy reduces myocardial damage and attenuates postoperative vasoactive mediator imbalance.
Xia
Zhengyuan
Z
Department of Anesthesiology, Affiliated Renmin Hospital, Wuhan University, PR China. xia@neuro.pharmacology.ubc.ca
Gu
Jiazhen
J
Ansley
David M
DM
Xia
Fang
F
Yu
Jinfu
J
D000293:Adolescent; D000975:Antioxidants / Q000008:administration & dosage; D001681:Biological Assay; D006348:Cardiac Surgical Procedures / Q000379:methods; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000379:methods*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D007262:Infusions, Intravenous; D007432:Intraoperative Period; D008297:Male; D015999:Multivariate Analysis; D008517:Phytotherapy / Q000379:methods*; D011183:Postoperative Complications / Q000517:prevention & control; D011336:Probability; D011379:Prognosis; D027561:Salvia miltiorrhiza; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013929:Thromboxane B2 / Q000097:blood*; D016896:Treatment Outcome
D000975:Antioxidants; D019332:Endothelin-1; D013929:Thromboxane B2