Boucek R J, Shelton M, Artman M, Mushlin P S, Starnes V A, Olson R D
Pediatr Res. 1984 Oct;18(10):948-52. doi: 10.1203/00006450-198410000-00008.
The effects of postnatal development on the systolic and diastolic responses to pharmacologic blockade of the slow inward calcium current were investigated in blood-perfused hearts isolated from immature (14-21-day-old) and adult rabbits. Isovolumic left ventricular developed pressure, resting pressure, and maximal rate of pressure development (+dP/dt) at cumulative doses of either verapamil, nifedipine, or diltiazem were determined by means of an intracavitary balloon. Myocardial contractile function in the immature heart was more sensitive to pharmacologic blockade of the slow inward calcium current than is the adult heart. Doses of verapamil, or nifedipine, that comparably reduced pretreatment developed pressure and +dP/dt were approximately 10-fold less in immature as compared to the adult heart. The dose of diltiazem which reduced developed pressure and dP/dt by 50% was 3-fold less in immature as compared to the adult heart. Verapamil and nifedipine decreased resting pressure in the adult but not in the immature heart. Conversely, diltiazem decreased resting pressure in the immature while not affecting resting pressure in adult hearts. Thus, postnatal cardiac development affects both the systolic and diastolic responses to calcium channel blockade. In addition, diltiazem appears to be qualitatively and quantitatively different from verapamil and nifedipine with respect to the age-related cardiac effects of calcium channel blockade.
在从未成熟（14 - 21日龄）和成年兔分离的血液灌注心脏中，研究了产后发育对药理学阻断缓慢内向钙电流时收缩和舒张反应的影响。通过心腔内气囊测定维拉帕米、硝苯地平或地尔硫䓬累积剂量下的等容左心室发育压力、静息压力和最大压力上升速率（+dP/dt）。未成熟心脏的心肌收缩功能比成年心脏对缓慢内向钙电流的药理学阻断更敏感。与成年心脏相比，能同等程度降低预处理时发育压力和 +dP/dt 的维拉帕米或硝苯地平剂量，在未成熟心脏中约低10倍。使发育压力和dP/dt降低50%的地尔硫䓬剂量，在未成熟心脏中比成年心脏低3倍。维拉帕米和硝苯地平降低成年心脏的静息压力，但不降低未成熟心脏的静息压力。相反，地尔硫䓬降低未成熟心脏的静息压力，而不影响成年心脏的静息压力。因此，产后心脏发育影响对钙通道阻断的收缩和舒张反应。此外，就钙通道阻断的年龄相关心脏效应而言，地尔硫䓬在质量和数量上似乎与维拉帕米和硝苯地平不同。
