Evaluation of cardiovascular effects of caffeine using telemetric monitoring in the conscious rat.
Caffeine (1,3,7 trimethylxanthine) affects the cardiovascular system, with potential toxic effects ranging from a moderate increase in heart rate to more severe cardiac arrhythmias. Telemetry transmitters were implanted in Wistar rats in the peritoneal cavity with a pressure catheter in the aorta and electrodes for electrocardiogram (ECG) recording subcutaneously. After a single oral administration of saline, each rat was administered single oral doses of 5, 15 and 45 mg/kg b.w. of caffeine. Caffeine was found to induce, to various degrees, a dose-dependent early increase in spontaneous physical activity, heart rate, dp/dt and systolic-diastolic blood pressure. No arrhythmias or visual changes were observed in the ECG complex. High doses induced more strong responses and of longer duration. The increase in systolic blood pressure at the median dose remained in the rats until 20 h after administration. However, the highest dose of caffeine (45 mg/kg b.w.) induced a biphasic response, with an early and pronounced increase in body temperature, spontaneous physical activity, systolic and diastolic blood pressure that later decreased, except for the systolic blood pressure. The results show that the dose level for long-lasting signs of intoxication to develop in the rat, in terms of effects on spontaneous physical activity, body temperature and cardiovascular function, was reached after a single oral dose of caffeine at 45 mg/kg b.w.
Ilbäck
Nils-Gunnar
NG
Toxicology Division, National Food Administration, Uppsala, Sweden. nils-gunnar.ilback@slv.se <nils-gunnar.ilback@slv.se>
Siller
Max
M
Stålhandske
Torbjörn
T
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002110:Caffeine / Q000633:toxicity*; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D013686:Telemetry / Q000379:methods*
D000697:Central Nervous System Stimulants; D002110:Caffeine