Validation of a human atrial trabecular preparation for evaluation of inotropic substances

Abstract

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 < 1.0 mm 2, resting force (RF) < 0.7 g, and developed force (DF) >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 × 10 −5 M), to 136% by amrinone (5.6 × 10 −4 M), and to 117% by ouabain (2 × 110 −7 M). The relative DF decreased with nifedipine and propranolol, with 50% inhibition for both drugs being 1.5 × 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.