Protective effects of N-n-butyl haloperidol iodide on myocardial ischemia-reperfusion injury in rabbits.
N-n-butyl haloperidol iodide (F2), a novel compound derived from haloperidol, was synthesized by our drugs research lab. The present study aims to evaluate the protective effects of F2 on myocardial ischemia-reperfusion injury in vivo, and to try to find the protective mechanism of F2. The animal model of myocardial ischemia-reperfusion injury was established by ligaturing rabbit's left ventricular branch of coronary artery for 40 min and removing the ligation later to reperfuse for 40 min. Different doses of F2 were intravenously injected before the onset of ischemia. The changes of hemodynamics were recorded during the experiment, and the activities of superoxide dismutase (SOD), creatine kinase (CK), Ca2+-ATPase, Na+,K+-ATPase and the level of malondialdehyde (MDA) of myocardial tissue were detected after reperfusion. Administration of F2 could dose-dependently ameliorate the hemodynamics of ischemia-reperfusion injured myocardium. During the course of reperfusion, MAP, LVSP, +/-dP/dt(max) in all F2 groups were obviously higher than those in the ischemia-reperfusion control group, and LVEDP were lower. F2 could also reduce the production of MDA, and maintain the activities of SOD, Ca2+-ATPase, Na+,K+-ATPase, and minimize the leakage of CK out of myocardial cells in a dose-dependent manner. These results suggested that F2 had apparent protective effects against myocardial ischemia-reperfusion injury.
Department of Pharmacology, Shantou University Medical College, Shantou 515041, PRC.
Fen-Fei
FF
Gao
Gang-Gang
GG
Shi
Jin-Hong
JH
Zheng
Bing
B
Liu
D000818:Animals; D003331:Coronary Vessels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology; D011817:Rabbits
C482574:N-n-butyl haloperidol iodide; D008315:Malondialdehyde; D006220:Haloperidol