Pathologic changes induced by 1-norepinephrine: Quantitative aspects ∗

Abstract

The effects of constant rate intravenous infusions of norepinephrine were studied in twenty-eight normal dogs sedated with morphine. The range of dose rates in this experiment was from 0.5 to 15 μg. per minute per kg. Blood levels of epinephrine and norepinephrine were determined in twelve animals for up to ten hours during constant rate infusions. The heart rate and blood pressure were recorded at frequent intervals. The reflex bradycardia was reversed in the animals by prolonged infusions of 1 or more μg. per minute per kg. of norepinephrine. In the animals in whom myocardial lesions developed, tachycardia and arrhythmia were regularly present. Death occurred due to cardiac arrest, massive cerebral hemorrhage or pulmonary edema in the animals infused with 10 μg. per minute per kg. for one-half to three hours, or 5 μg. per minute per kg. for six hours. Postmortem examination was performed on all animals. The tissue changes were described and correlated with dosage rate and blood catecholamine levels. The experimental results were discussed in the light of the mounting frequency of myocarditis due to pressor amine therapy in human beings and preventive measures in the form of a maximum safe dosage were offered.