Anderson P G, Digerness S B, Sklar J L, Boor P J
Department of Pathology, University of Alabama, Birmingham 35294.
Toxicol Pathol. 1990;18(4 Pt 1):497-510.
The isolated perfused rat heart model can be used to evaluate cardiotoxicity, and is especially useful in distinguishing direct vs indirect cardiac injury. Various perfusion systems can be used to characterize the pathophysiologic as well as morphologic changes induced by drugs or chemicals of interest. The isolated perfused heart was used in the studies described herein to characterize the mechanism of allylamine cardiotoxicity. Rat hearts were perfused with Krebs-Henseleit buffer containing 10 mM allylamine and a latex balloon was inserted into the left ventricle to monitor pressure. Coronary flow in hearts perfused with 10 mM allylamine was similar to control hearts at 5, 10, and 30 min, but was reduced by 1 hr (11.5 +/- 0.6 ml/min/g wet heart weight vs 16.0 +/- 0.7, p less than 0.01). Peak left ventricular systolic pressure increased in hearts perfused with allylamine for 5 min (156 +/- 8 mm Hg vs 103 +/- 9, p less than 0.01), but by 2 hr was decreased compared to controls (89 +/- 6 vs 105 +/- 5, p less than 0.05). End diastolic pressure was markedly increased at 2 hr (58 +/- 3 vs 4 +/- 0.8, p less than 0.01). Morphologically, allylamine perfused hearts exhibited significant contraction band changes as well as numerous cells with marked swelling of the sarcoplasmic reticulum. The findings in this study suggest that allylamine produces direct myocardial damage that appears to be independent of coronary flow. These studies demonstrate that the isolated perfused rat heart model can be used to evaluate mechanisms of acute cardiotoxicity.
离体灌注大鼠心脏模型可用于评估心脏毒性，尤其有助于区分直接与间接心脏损伤。各种灌注系统可用于分析由感兴趣的药物或化学物质引起的病理生理以及形态学变化。本文所述研究中使用离体灌注心脏来分析烯丙胺心脏毒性的机制。用含10 mM烯丙胺的Krebs-Henseleit缓冲液灌注大鼠心脏，并将一个乳胶球囊插入左心室以监测压力。用10 mM烯丙胺灌注的心脏在5、10和30分钟时的冠脉流量与对照心脏相似，但在1小时时降低（11.5±0.6 ml/min/g湿心脏重量对16.0±0.7，p<0.01）。用烯丙胺灌注5分钟的心脏左心室收缩压峰值升高（156±8 mmHg对103±9，p<0.01），但与对照相比，2小时时降低（89±6对105±5，p<0.05）。2小时时舒张末期压力显著升高（58±3对4±0.8，p<0.01）。形态学上，用烯丙胺灌注的心脏表现出明显的收缩带变化以及许多肌浆网明显肿胀的细胞。本研究结果表明烯丙胺产生直接心肌损伤，且似乎与冠脉流量无关。这些研究证明离体灌注大鼠心脏模型可用于评估急性心脏毒性机制。
