Effects of N-n-butyl haloperidol iodide on rat myocardial ischemia and reperfusion injury and L-type calcium current.
OBJECTIVE
To study the effects of N-n-butyl haloperidol iodide (F2) on rat heart ischemia/reperfusion (I/R) injury and L-type calcium current (ICa) in rat ventricular myocytes.


METHODS
Rat heart I/R injury was induced by occluding the left anterior descending coronary artery for 30 min and restoring perfusion for 30 min. F2 (1, 2, and 4 mg/kg) were i.v. injected before ischemia. Plasma creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), glutamic-oxaloacetic transaminase (GOT), malondialdehyde (MDA) concentrations, and superoxide dismutase (SOD) activity were measured. The pathologic changes of I/R myocardium were assessed by the transmission electron microscopy. Single rat ventricular myocyte was obtained by enzymatic dissociation method. The currents were recorded with the whole-cell configuration of the patch-clamp technique.


RESULTS
F2 reduced the release of CK, CK-MB, LDH, HBDH and GOT, preserved the activity of SOD, and decreased the MDA contents dose-dependently. For morphology, F2 mollified the pathologic changes of myocardium induced by I/R injury. F2 1 micromol/L decreased ICa from (1775+/-360) pA to (464+/-129) pA (n=8, P<0.01) and shifted the current-voltage of ICa upward, without affecting the voltage-depend-ent properties of ICa.


CONCLUSIONS
F2 played a protective role against rat heart I/R injury in a dose-dependent manner, and inhibited ICa in rat ventricular myocytes. The cardioprotective and vasodilatory mechanisms of F2 may be related to its inhibitory effect on L-type calcium channel.
Huang
Zhan-Qin
ZQ
Department of Pharmacology, Shantou University Medical College, Shantou 515031, China.
Shi
Gang-Gang
GG
Zheng
Jin-Hong
JH
Liu
Bing
B
D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D006220:Haloperidol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D008854:Microscopy, Electron; D017202:Myocardial Ischemia / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D009206:Myocardium / Q000648:ultrastructure; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; C482574:N-n-butyl haloperidol iodide; D006220:Haloperidol