The effects of cardioteratogenic doses of caffeine on cardiac function in the 3‐day chick embryo

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Abstract
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.