The Effect Of Vanadium On The Function Of Heart Of Rat And Underlying Mechanism

Background:Substantial epidemiological evidence suggested that fine particulate matter air pollution(Particulate matter,PM)especially fine PM whose diameter no more than 2.5μm had adverse human health effects and PM was a risk factor for cardiovascular disease.Many studies showed that PM metal content especially the transit metal,vanadium in valence states +5(V5+),play a vital role in the health effects associated with PM exposure,in particular that associated with exposure to emission source PM.Previous researches had revealed that the adverse cardiac events linked with elevated air pollutants included serious ventricular arrhythmias,myocardial infarction and heart failure,etc.A large number of studies were identified to assess specific mechanistic pathways underlying the cardiovascular effects of PM from the angle of heart-rate variability,electrocardiogram and estimations of ejection fraction and wall abnormalities in imaging studies,and clotting parameters,cytokines,lipid profiles,and forearm blood flow.However,no one had demonstrated the potential mechanisms at single cell level yet.Therefore,to further investigate the mechanism experiments of animals at single cell level were recommended.Aim:(1)To observe the effect of V5+ on the hemodynamic indexes of the isolated rat heart.(2)To observe the effect of V5+ on the concentration of free calcium of single cardiomyocyte in order to analysis the underlying mechanism.(3)To observe the effects of V5+ on L-type calcium channel and sodium calcium exchanger by using patch clamp technique.Methods:(1)The effects of V5+ on the hemodynamic indexes were observed as LVSP-LVDP,LVDP,+dp/dtmax,-dp/dtmax by Langendorff isolated heart perfusing.(2)The effects of V5+ on the concentration of free calcium of single cardiomyocyte were observed by using CCD ionic imaging system.F340/F380 measured by the CCD ionic imaging system represented the concentration of free calcium of single cardiomyocyte.(3)The effects of V5+ on L-type calcium channel and sodium calcium exchanger were observed by using whole cell voltage clamp technique.Results:(1)V5+ could enhance LVSP-LVDP,LVDP,+dp/dtmax,in a dose-dependent manner and cause arrhythmia;(2)V5+ could raise the cytosolic free calcium concentration of cardiac myocytes.(3)V5+ could enhance and inhibit the L-Type calcium current and Na+/Ca2+ exchange current,respectively,in a dose-dependent manner,but not change the voltage dependent property of L-Type calcium.Conclusion:(1)V5+ enhanced the intensity and speed of contraction and inhibited relaxation of isolated heart of rat in a dose-dependent manner.V5+ with high concentration could cause arhythmia obviously.(2)V5+ can raise the cytosolic free calcium concentration of cardiac myocytes in a dose-dependent manner,which is in accord with the results before.(3) V5+ can enhance and inhibit the L-Type calcium current and Na+/Ca2+ exchange current, respectively,in a dose-dependent manner,which was a very important reason that cause the high concentration of free calcium of cardiomyocytes.