Schiffmann Holger, Rizouli Vicky, Luers Frank, Hackmann Frank, Hoebel Dyrken, Pfahlberg Annette, Hellige Gerhard
Department of Pediatric Cardiology and Intensive Care, University of Goettingen, Goettingen D-37075, Germany.
Pediatr Res. 2003 Dec;54(6):875-84. doi: 10.1203/01.PDR.0000091286.21994.E5. Epub 2003 Aug 20.
Na+-channel modulators exert their positive inotropic action without affecting the adenylate-cyclase pathway by an increase in the open probability of the sarcolemmal Na+ channels. Although inotropic effects in neonatal hearts are less pronounced compared with adult hearts, the Na+-channel modulator BDF 9148 increases contractility and relaxation velocity in immature myocardium. Effects on hemodynamics and myocardial energetics are not known. Therefore, we studied the Na+-channel modulator BDF 9148 in isolated antegrade perfused rabbit hearts of different ages (2-28 d) and compared the effects with isoproterenol, enoximone, and ouabain. ANOVA showed significant effects in the concentration response curves for heart rate, stroke volume, cardiac output, and oxygen consumption but not for myocardial efficiency (p = 0.06). Age-dependent differences were observed for heart rate and stroke volume. Administration of BDF 9148 resulted in a maximal increase in stroke volume and cardiac output up to 25% in neonatal and 40% to 60% in adult preparations. Heart rate decreased by 15% in adult hearts only. Myocardial oxygen consumption was increased in a concentration-dependent manner between 25% in neonatal and 50% in adult hearts. Myocardial efficiency was increased by 35% in adult and by 10% in neonatal preparations. Although positive hemodynamic and energetic effects were less pronounced in immature compared with adult hearts, neonatal hearts also profited from the administration of the Na+-channel modulator BDF 9148. Further studies are necessary to clarify the risk of arrhythmia during application of Na+-channel modulators such as BDF 9148.
钠通道调节剂通过增加肌膜钠通道的开放概率来发挥其正性肌力作用，而不影响腺苷酸环化酶途径。尽管与成年心脏相比，新生儿心脏的正性肌力作用不太明显，但钠通道调节剂BDF 9148可增加未成熟心肌的收缩力和舒张速度。其对血流动力学和心肌能量代谢的影响尚不清楚。因此，我们在不同年龄（2 - 28天）的离体顺行灌注兔心脏中研究了钠通道调节剂BDF 9148，并将其作用与异丙肾上腺素、依诺昔酮和哇巴因进行了比较。方差分析显示，在心率、每搏输出量、心输出量和氧耗的浓度反应曲线中有显著影响，但对心肌效率无显著影响（p = 0.06）。观察到心率和每搏输出量存在年龄依赖性差异。给予BDF 9148后，新生儿心脏的每搏输出量和心输出量最大增加25%，成年心脏增加40%至60%。仅成年心脏的心率降低了15%。新生儿心脏的心肌氧耗以浓度依赖性方式增加，在新生儿中为25%，在成年心脏中为50%。成年心脏的心肌效率提高了35%，新生儿心脏提高了10%。尽管与成年心脏相比，未成熟心脏的正性血流动力学和能量学效应不太明显，但新生儿心脏也从钠通道调节剂BDF 9148的给药中获益。有必要进一步研究以阐明应用BDF 9148等钠通道调节剂期间心律失常的风险。
