Cardiovascular And Renal Effects Of Indomethacin In Newborn Dogs

The cardiovascular effects of indomethacin were studied acutely in 9 newborn dogs (2-32 days) using the radioactive microsphere reference organ technique. Indomethacin, 0.3 mg/kg intravenously, produced a 22% drop in cardiac output (CO) from 224±31* to 175±26 ml/kg/min (p<.05). Renal blood flow fell slightly from 1.6±.2* to 1.3±.2 ml/gm/min (p<.05). Renal inner cortical (IC) and outer cortical (OC) blood flow both fell (p<.01), but did so proportionately with no resultant change in IC/OC ratio. There were no changes in blood flow to the GI tract, heart or lungs. Of particular interest is that although in animals over 7 days (n=5) indomethacin produced no change in cerebral blood flow (CBF), in 2-day-old puppies (n=3) it produced a 47% fall in CBF (p<.05). Indomethacin produced no significant changes in glomerular filtration rate or potassium excretion, but there was a transient drop in tubular sodium reabsorption (p<.01) which rapidly returned to control values after 1½ hours. In summary, indomethacin in a dose currently being used clinically causes small, but statistically significant decreases in CO and renal blood flow, with minimal changes in renal function. However, in very young animals, this dose of indomethacin results in a marked drop in cerebral blood flow not found in older animals.