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目的:比较抗钠钙交换体(NCX)特异位点(α-1重复序列124HNFTAGDLGPSTIVGSAAFNMF145)抗体、传统强心药哇巴因以及L型Ca2+通道激动剂(±)Bay K8644对离体大鼠心脏和血管功能的影响,以探求新的强心作用靶点。方法:选用成年大鼠,体重250～300 g,快速分离心脏和胸主动脉,利用Langendorff离体心脏灌流装置和血管环张力测定系统观察10 nmol/L、20 nmol/L和40 nmol/L抗NCX特异位点抗体以及哇巴因(0.5mmol/L)、(±)Bay K8644(0.1 mmol/L)对心脏血流动力学指标左室发展压、左心室内压上升/下降最大速率(±dp/dt max)、冠脉阻力以及胸主动脉环张力的影响。结果:10 nmol/L、20 nmol/L和40nmol/L抗NCX特异位点抗体剂量依赖性地使大鼠离体心脏左室发展压、+dp/dt max和-dp/dt max增加,表明心脏收缩和舒张效率均增强。给药过程中均没有发生心律失常。哇巴因(0.5 mmol/L)和(±)Bay K8644(0.1 mmol/L)对正常离体灌流大鼠心脏左室发展压及+dp/dt max也有增强作用,作用强度与抗NCX特异位点抗体(40 nmol/L)的作用相当,但(±)Bay K8644(0.1 mmol/L)对-dp/dt max无明显影响,哇巴因(0.5 mmol/L)则有使-dp/dt max下降的趋势。哇巴因(0.5 mmol/L)在给药5 min后,多数离体心脏出现≥5 beats/min的早博,(±)Bay K8644(0.1 mmol/L)给药过程中离体大鼠心脏没有出现心律失常。结论:抗NCX特异位点抗体可以同时增强离体灌流大鼠心脏的收缩和舒张活动,并且不增加心律失常的发生率,同时对灌流心脏冠脉阻力以及离体大鼠的胸主动脉环张力也没有显著影响。
OBJECTIVE: To compare the inhibitory effects of antibodies against naive calcium exchanger (NCX) (α-1 repeats 124HNFTAGDLGPSTIVGSAAFNMF145), conventional cardiac oubupine and L-type Ca2 + channel agonist ± K8644 on isolated rat heart and Vascular function in order to explore the new target of cardiac function. Methods: The heart and thoracic aorta were isolated rapidly from 250 to 300 g in adult rats. The effects of 10 nmol / L, 20 nmol / L and 40 nmol / L anti-tumor were observed by Langendorff perfusion device and vascular ring tension measurement system NCX specific site antibody and left ventricular ejection fraction (LVEDP) and left ventricular pressure (± mmol) of K8644 (0.1 mmol / L) dp / dt max), coronary resistance and thoracic aortic ring tension. RESULTS: Anti-NCX specific antibodies at doses of 10 nmol / L, 20 nmol / L and 40 nmol / L increased left ventricular LV pressure, increased + dp / dt max and -dp / dt max in isolated rat hearts Systolic and diastolic efficiency are enhanced. Arrhythmia did not occur during administration. Ouabain (0.5 mmol / L) and (±) Bay K8644 (0.1 mmol / L) also enhanced left ventricular LV + dmax and + dp / dt max in isolated perfused rat hearts, The effect of point antibody (40 nmol / L) was comparable, but (±) Bay K8644 (0.1 mmol / L) had no significant effect on -dp / dt max and ouabain max downward trend. After administration of ouabain (0.5 mmol / L) for 5 min, most isolated hearts showed premature beats ≥5 beats / min and the isolated rat heart during administration of (±) Bay K8644 (0.1 mmol / L) No arrhythmia occurred. CONCLUSION: The anti-NCX specific antibody can enhance the systolic and diastolic activities of isolated perfused rat heart at the same time without increasing the incidence of arrhythmia. Meanwhile, the coronary resistance of perfused heart and thoracic aortic ring tension Nor significant effect.