Analysis Of Ouabain Toxicity On Rat Heart

Objective: 1.To observe the effects of metoprolol on arrhythmia induced by ouabain and to explore the mechanism of ?-blocker in the treatment of digitalis poisoning.2.The Langendorff isolated heart perfusion system was applied to analyze the timed dose-response relationship of ouabain's inhibitory action on isolated rat heart.Methods:1.Langendorff perfusion system was used for this part,SD rats were randomly divided into 5 groups: normal control group,model group,4?mol/L?20?mol/L?100?mol/L metoprolol group,8 rats in each group;record the number of PVB,the incidence of VF and VT within 60 minutes;2.Femoral vein was used for drug injection in vivo experiment,SD rats were randomly divided into 5 groups: normal control group,model group,0.4mg/kg,2mg/kg,10mg/kg metoprolol group,8 rats in each group;observe the occurrence time of premature ventricular contractions(VP),ventricular tachycardia(VT),bundle branch block(BBB)and ventricular fibrillation(VF)and cardiac arrest(CA)time,calculate ouabain dosage when the above phenomena occurs.3.Langendorff perfusion system for isolated heart perfusion test,ouabain was configured to six different concentration ranged from 3?mol/ L to 1000?mol/ L,record the amplitude of variation of LVDP and LVEDP.Results:1.In this part,there was no significant difference between metoprolol group and ouabain model group(P>0.05).2.In this vivo experiment,metoprolol may be associated with the delay of ouabain-induced-ventricular arrhythmia(premature ventricular beat,short array and persistent ventricular tachycardia)appearing time,but also leads to a earlier occurring time of conduction block(bundle branch block and atrio-ventricular block),the incidence of ventricular fibrillation was significantly reduced,as a result,the survival time of animals was significantly prolonged.3.It was found in the study of contractile function that with the increase of Ouabain concentration(3~1000?mol/L),the degree of inhibiting was increased,the latency time was shortened,the top-reaching time at low concentrations(<30?mol/L)was prolonged while at higher concentration(>100?mol/L)was shortened,the average inhibition rate was increased;The analyses of diastolic function found that with the increase of concentration of Ouabain(3~1000?mol/L),the degree of end diastolic pressure elevation was increased,the latency time was shortened,the top-reaching time was prolonged,the average elevation rate was increased.Conclusion:1.Ouabain steadily induced the arrhythmia in isolated rat heart and in vivo condition,metoprolol may not resist ouabain-cardiaotoxicity in vitro condition,but may counteract ouabain-induced ventricular arrhythmia in vivo condition,but increased the conduction block caused by ouabain.2.The results indicate that not only the GDRR but also the TDRR exists in the inhibitory action of oubain on rat heart.