| Haloperidol (Hal) is used as the antipsychotic drug in clinic by blocking the receptor of dopamine in the central nervous system. Our previous research showed that Hal could inhibit the contraction of coronary artery strips induced by KC1, relieve the symptoms of aanginal attacks, and improve the ischemia change of ECG in patients. However, it was not used as an anti-myocardial ischemia drug due to its extrapyramidal adverse reactions. It was imaged to change the chemical structure of Hal, and make it impossible to pass through the blood-brain barrier and diffuse into brain for avoiding the central nerve reaction and keeping the obvious effect of dilating coronary artery. So, we synthesized a series of quaternary ammonium salt derivations of Hal. Among these chemical compounds, F2 (N-n-butyl haloperidol iodide) was screened as its cardiovascular action was preserved without the adverse reactions. (The chemical structure of Hal and F2 were showed as Fig1, 2). In this article, the effects of F2 onischemia-reperflision injury were studied.The effects of F2 on hemodynamics of myocardial ischemia-reperfusioninjury in ratsEthyl carbamate-anesthetized (40%), open-chested, Wistar rats of either sex weighing (264 ?19)g with a cannula inserting into the right femoral artery and a catheters inserting into the left ventricle through right common carotid artery were instrumented for hemodynamic measurements. Myocardial ischemia was produced by briefly exteriorizing the heart and placing a 5-0 silk suture around the left coronary artery (LCA), approximately 2 to 3 mm from its origin, effectively occluding the vessel. The left coronary artery was ligated during the surgical preparation and induction of regional ischemia 60 min, then removed the ligation later for reperfusion 60 min. Sham-operated control rats (sham) underwent the same surgical procedures, except that the suture, which was passed under the left coronary artery, was not tied. The ECG of limb lead II was used to document the process of myocardial ischemia and reperfusion. Seventy rats were randomly assigned to one of seven groups: Sham-operated group (Sham, n=10), Control group (I/R, n=10), Solvent group (polyethylene glycol 400, PEG 400, n=10), @ Verapamil group (Ver, n=10), groups F2 of three different dosages (each group, n=10). Saline, PEG 400, Verapamil and three F2 groups of different dosages (0.125 mg/kg 0.5 mg/kg 2 mg/kg) were injected into the sublingual vein 5 min before the ischemia. The changes of hemodynamics, including heart rate (HR), mean aortic pressure (AP), leftventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP),left ventricular mean pressure (LVAP), left ventricular end-diastolic pressure(LVEDP) and positive and negative maximal values of the first derivative of leftventricular pressure were recorded with Newcenturyrecording-and-analyzing system software during the experiment.The effects of F2 on the infarct size of hearts in rat models of myocardialischemia-reperfusion.The in vivo animal model of myocardial ischemia-reperfusion injury wasreconducted by ligating the left coronary artery for 60 min and removing theligation later to reperfuse for 60 min. At the end of the 60 min period ofreperfusion, the left coronary artery was religated. Evans blue dye (1.5 ml, 5.0 %)was injected into the sublingual vein to delineate the area of risk (AR) in vivo.With this technique, the previously nonischemic myocardium appears blue,whereas the previously ischemic myocardium (area of risk) remains unstained.The heart was excised and submerged in cold buffer to remove excess EvansBlue, then stored 10 min at -20. Frozen hearts were sliced into eight 1-1.5mm transverse sections parallel to the atrioventricular groove from apex to base.The atrial tissue was discarded. Sections of the ventricle were incubated with 1%TTC (2, 3, 5-triphenyltetrazolium chloride) solution for 15 min at 37. Thismethod reliably distinguishes necrotic myocardium (which appears pale yellow)fro...
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