Bruyere H J, Michaud B J, Gilbert E F, Folts J D
J Appl Toxicol. 1987 Jun;7(3):197-203. doi: 10.1002/jat.2550070309.
The effects on embryonic cardiac function of caffeine administration (two non-cardioteratogenic and two cardioteratogenic doses) to Hamburger-Hamilton stage 19 (3-3 1/2 days of incubation) chick embryos were investigated. Using microcinephotoanalysis, we have determined that caffeine (1.0-4.7 mg/egg), within the initial three hours after treatment, produced a dose-dependent decrease in end diastolic volume, stroke volume, cardiac output, and ejection fraction. These effects were sustained for a longer period of time following dosing at a cardioteratogenic level (3.5-4.7 mg/egg). Caffeine (1.0-4.7 mg/egg) also increased cardiac rate with a maximum increase of 30% seen 60 minutes after treatment with doses of 2.7 mg and 3.5 mg. However, the increase in cardiac rate was not related to dose. At 20 hours after treatment, caffeine increased stroke volume, ejection fraction and cardiac output relative to the controls. End-diastolic volume and cardiac rate were not changed. These results are evidence for a biphasic effect of cardioteratogenic dosing with caffeine during the first 20 hours after treatment--initially a sustained decrease in cardiac output, suggesting decreased flow through the embryonic heart, followed by an increase in ejection fraction, suggesting increased cardiac workload.
研究了对处于汉伯格-汉密尔顿第19阶段（孵化3 - 3.5天）的鸡胚胎给予咖啡因（两种非心脏致畸剂量和两种心脏致畸剂量）对胚胎心脏功能的影响。通过显微电影摄影分析，我们确定咖啡因（1.0 - 4.7毫克/枚蛋）在处理后的最初三小时内，使舒张末期容积、每搏输出量、心输出量和射血分数呈剂量依赖性降低。在给予心脏致畸剂量（3.5 - 4.7毫克/枚蛋）后，这些影响持续的时间更长。咖啡因（1.0 - 4.7毫克/枚蛋）还增加了心率，在用2.7毫克和3.5毫克剂量处理60分钟后，心率最大增加了30%。然而，心率的增加与剂量无关。在处理20小时后，相对于对照组，咖啡因增加了每搏输出量、射血分数和心输出量。舒张末期容积和心率没有变化。这些结果证明了在处理后的前20小时内，心脏致畸剂量的咖啡因具有双相效应——最初心输出量持续下降，表明流经胚胎心脏的血流量减少，随后射血分数增加，表明心脏工作负荷增加。
