Morphine-induced tachycardia in fetal lambs: a bell-shaped dose-response curve

A dose-response analysis of the effects of morphine on fetal heart rate (FHR) and blood pressure (FBP) was conducted in 28 chronically instrumented fetal lambs. Morphine was infused directly to the fetus at doses ranging from 0.075 to 40 mg/hr. At doses below 0.15 mg/hr, morphine did not result in significant changes in FHR or FBP. With increasing doses of morphine, fetal tachycardia was observed without significant changes in FBP, and the peak response (38.3 +/- 8%) in FHR was reached at a dose of 2.5 mg/hr. Further increases in dose were associated with a decrease in the magnitude of response. This resulted in a bell-shaped dose-response curve. This tachycardia was completely abolished by either naloxone or propranolol pretreatment. These results indicate that i.v. morphine administrated produces tachycardia in unanesthetized unrestrained fetal lambs, and this effect is mediated via specific opioid receptors and involves the beta adrenergic system.