儿茶酚胺α_2受体作用剂对单甲脒中毒豚鼠心脏毒性的影响

Effect of adrenergic-α_2 antagonists and agonists on the cardiovascular toxicity induced by monoformamidine in guinea pigs

目的 探讨脒类农药中毒致死的关键机制。方法 用生理多导仪观察儿茶酚胺α2 受体作用剂对单甲脒染毒豚鼠心血管功能的影响。结果 α2 受体抑制剂可降低单甲脒中毒豚鼠的心脏毒性。单甲脒染毒后 1h豚鼠的心率、收缩压和心肌收缩力 (dp/dt最大值 ) :育亨宾组分别为(186± 35 )次 /min、(80± 16 )mmHg(1kPa=7.5mmHg)和 (6 12± 32 7) mmHg/s;酚妥拉明组分别为 (16 5± 18)次 /min、(84± 2 1)mmHg和 (5 0 0± 334 )mmHg/s。明显高于对照组的 (12 0± 2 2 )次 /min、(6 5± 12 )mmHg和 (2 35± 133)mmHg/s,差异有显著性 (P <0 .0 5 ) ,且改善心电图 ,减少死亡。而α2 受体兴奋剂作用相反 ,单甲脒染毒后 1h豚鼠的心率、收缩压和心肌收缩力 (dp/dt最大值 ) :可乐定组分别为 (82± 39)次 /min、(42± 7)mmHg和 (87± 78)mmHg/s;利血平组分别为 (5 9± 32 )次 /min、 (2 8± 10 )mmHg和 (15 1± 77)mmHg/s,明显低于对照组 ,差异有显著性 (P <0 .0 5 )。结论 脒类农药兴奋中枢儿茶酚胺α2 受体 ,经负反馈影响心血管功能 ,终因循环衰竭致死。

Objective To study the dominant mechanism of monoformamidine intoxication. Methods Adrenergic α 2 antagonists(yohimbine and phentolamine) and agonists(clonidine and reserpine) were given in guinea pigs just before administration of monoformamidine.Results Antagonists could mitigate the cardiovascular changes.The heart rate, blood pressure,and myocardiac contraction(dp/dt max) after 1 h of intoxication were (186±35)beat/min,(80±16) mm Hg(1 kPa=7.5 mm Hg) and (612±327) mm Hg/s respectively in yohimbine group;(165±18)beat/min,(84±21) mm Hg and (500±334) mm Hg/s in phentolamine group,significantly higher than (120±22)beat/min,(65±12) mm Hg and (235±133) mm Hg/s in control group( P <0.05).ECG was improved and death was reduced as well in both antagonist groups.On the contrary,agonists worsened such cardiovascular effects.The heart rate,blood pressure,and myocardiac contraction(dp/dt max) after 1 h of intoxication were (82±39)beat/min,(42±7) mm Hg and (87±78) mm Hg/s respectively in clonidine group;(59±32)beat/min,(28±10) mm Hg and (151±77) mm Hg/s in reserpine group significantly lower than the control group( P <0.05). Conclusion The dominant mechanism of intoxication is the agonistic effects of monoformamidine on the adrenergic α 2 receptor,which may affect the cardiovascular system through negative feedback leading to lethal circulatory failure.