Labow R S, Desjardins S, Keon W J
University of Ottawa Heart Institute, Ottawa Civic Hospital, ON, Canada.
J Pharmacol Methods. 1991 Dec;26(4):257-68. doi: 10.1016/0160-5402(91)90036-5.
Assessment of cardioactive substances is usually performed using animal tissue, with the effects being extrapolated to humans, thereby potentially introducing errors due to species differences. In order to validate the use of human atrial tissue, known positive and negative inotropic agents were tested on trabeculae obtained from patients' atrial appendages at the time of cardiac surgery requiring, cardiopulmonary bypass. Trabeculae were selected according to strict criteria: cross-sectional area less than 1.0 mm2, resting force (RF) less than 0.7 g, and developed force (DF) greater than 0.8 g. Each trabecula received only one drug in a cumulative dose manner. Where necessary, the vehicle used to dissolve or stabilize the drug solution was also tested. In addition, the relative DF of "no-drug," "time-only" controls were measured during the same time period. After adjusting for the effect of time on the preparation, relative DF was increased to 157% by dobutamine (1.5 x 10(-5) M), to 136% by amrinone (5.6 x 10(-4) M), and to 117% by ouabain (2 x 10(-7) M). The relative DF decreased with nifedipine and propranolol, with 50% inhibition for both drugs being 1.5 x 10(-7) M. Although human ventricular muscles might be more appropriate to use in order to determine the effects observed with the whole heart, they are extremely difficult to obtain on a regular basis. The results of this study show that the atrial trabecular preparation offers an acceptable alternative.
对心脏活性物质的评估通常使用动物组织进行，其结果外推至人类，因此可能因物种差异而引入误差。为了验证人体心房组织的适用性，在需要体外循环的心脏手术时，对取自患者心房附件的小梁进行了已知的正性和负性肌力药物测试。小梁根据严格标准选取：横截面积小于1.0平方毫米，静息力（RF）小于0.7克，收缩力（DF）大于0.8克。每根小梁仅以累积剂量方式接受一种药物。必要时，还对用于溶解或稳定药物溶液的赋形剂进行了测试。此外，在同一时间段内测量了“无药物”“仅时间”对照组的相对DF。在调整时间对标本的影响后，多巴酚丁胺（1.5×10⁻⁵M）使相对DF增加至157%，氨力农（5.6×10⁻⁴M）使其增加至136%，哇巴因（2×10⁻⁷M）使其增加至117%。硝苯地平和普萘洛尔使相对DF降低，两种药物50%抑制时的浓度均为1.5×10⁻⁷M。尽管为了确定在整个心脏观察到的效应，使用人心室肌可能更合适，但定期获取极为困难。本研究结果表明，心房小梁标本提供了一种可接受的替代方法。
