Effect of ursodeoxycholic acid on ischemia/reperfusion injury in isolated rat heart.
In this study, the effects of ursodeoxycholic acid (UDCA) on ischemia/reperfusion injury were investigated on isolated heart perfusion model. Hearts were perfused with oxygenated Krebs-Henseleit solution (pH 7.4, 37 degrees C) on a Langendorff apparatus. After equilibration, isolated hearts were treated with UDCA 20 to 160 microM or vehicle (0.04% DMSO) for 10 min before the onset of ischemia. After global ischemia (30 min), ischemic hearts were reperfused and allowed to recover for 30 min. The physiological (i.e. heart rate, left ventricular developed pressure, coronary flow, double product and time to contracture formation) and biochemical (lactate dehydrogenase; LDH) parameters were evaluated. In vehicle-treated group, time to contracture formation was 21.4 min during ischemia, LVDP was 18.5 mmHg at the endpoint of reperfusion and LDH activity in total reperfusion effluent was 54.0 U/L. Cardioprotective effects of UDCA against ischemia/reperfusion consisted of a reduced TTC (EC25=97.3 microM), reduced LDH release and enhanced recovery of cardiac contractile function during reperfusion. Especially, the treatments of UDCA 80 and 160 microM significantly increased LVDP and reduced LDH release. Our findings suggest that UDCA ameliorates ischemia/reperfusion-induced myocardial damage.
Lee
W Y
WY
Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, Suwon, Korea.
Han
S H
SH
Cho
T S
TS
Yoo
Y H
YH
Lee
S M
SM
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D002317:Cardiovascular Agents; D014580:Ursodeoxycholic Acid; D007770:L-Lactate Dehydrogenase