莫沙比利对大鼠离体心脏心功能和心律的影响

目的 观察5-HT4受体激动剂莫沙比利（mosapride）对大鼠离体心脏心律和心功能的影响,并探讨可能的电生理学机制.方法 采用成年健康雄性SD大鼠建立离体心脏Langendorff主动脉逆行灌流系统.将实验大鼠分成4组：正常对照组,莫沙比利1 μmol/L组、10 μmol/L组和西沙比利阳性对照组,每组8只大鼠.正常对照组用台氏液灌流,实验组在台氏液中分别加用莫沙比利1μmol/L、10 μmol/L和西沙比利1 μmol/L行心脏主动脉逆行灌流,记录心电图和心功能指标.观察给药30 min内心率、左室收缩压（LVSP）、左室舒张压（LVDP）、左室收缩最大上升速率（＋dp/dtmax）、左室舒张最大下降速率（-dp/dtmax）的变化,分别累计期前收缩次数（PVB）、室速（VT）和室颤（VF）发生率,比较两种5-HT4受体激动剂对心律和心功能的影响.结果 在大鼠离体心脏给药30 min内,1μmol/L和10 μmol/L莫沙比利对大鼠心律和心功能均无明显影响（P＞0.05）,1μmol/L莫沙比利不诱发心律失常,10 μmol/L莫沙比利可引起偶发PVB（2±3）个.阳性对照药西沙比利（1 μmol/L）可轻度加快心率,对心功能无明显影响,但可诱发明显的心律失常,给药30 min内,PVB（81±13）个,VT和VF发生率分别为25.0％和12.5％（P＜0.01）.结论 5-HT4受体激动剂莫沙比利对大鼠离体心脏心律和心功能无明显影响,可以作为一种替代西沙比利的安全促胃肠动力药.

The effects of mosapride on rat heart function and rhythm in an in vitro study

Objective To study the effects of 5-HT4 receptor agonist mosaprlde on heart function and rhythm in isolated rat heart and involved electrophysiologic mechanisms. Methods The adult healthy male SD rats were divided into four groups, control, mosapride groups at 1 and 10 Ixmol/L respectively and cisapride at 1 txmol/ L group. The isolated hearts were fixed on Langendorff aortic retrograde perfusion system, ECGs and heart function- al indexes were recorded simultaneously. The control group hearts were perfused with Tyrode solution, and the ex- perimental group hearts were treated with Tyrode solution containing mosapride and cisapride, respectively. The heart rate, left ventricular systolic pressure （LVSP）, left ventficular diastolic pressure （LVDP）, maximal rate of pressure inereasesd （＋dp/dtm）, maximal, rate of pressure deereasesd （-dp/dtm）, the total of premature ventrieu- lar contraction （PVB）, the incidence of ventricular tachycardia （VT） and ventricular fibrillation （VF） within 30 minutes after drugs administration were monitored and compared. Results In isolated Langendorff-perfused hearts, 1 and 10 /xmol/L mosapride had no effects on heart rate and function. There were only fortuitous PVB （2＋ 3） elicited by 10 μmol/L mosapride. Cisapride at 1 Ixmol/L mildly accelerated heart rate but elicited singnificant rhythm disturbances, the total of PVB were（81 13）, 25.0%（2/8） of hearts exhibited VT, 12.5% （1/8） exhibited VF （n=8, P〈0.01 ）. Conclusion As a 5-HT4 receptor agonist, mosapride is a more secure gastrointestinal proki- netic agent with no side effects on rat heart function and rhythm.