Abstract

The effects of a one-hour intravenous infusion of norepinephrine (NE; 2.5 µg/kg/min) were studied in anesthetized dogs, both intact and with cardiopulmonary bypass. In the intact animals, tolerance to NE infusions developed within approximately 15 minutes. manifested as failure to maintain the initially increased blood pressure and contractile force. When the NE infusion was terminated in the intact animals, the blood pressure fell rapidly to very low levels (postinfusional hypotension) and the left ventricular contractile force and heart rate decreased sharply. When the cardiopulmonary bypass was used to maintain a constant cardiac output, the infusion of NE resulted in a sustained increase in blood pressure. When the NE infusion was terminated, the blood pressure fell less rapidly and did not reach the shock levels which were seen with intact animals. A sharp drop in pH seen with the cardiopulmonary bypass animals indicates that, as regards the peripheral vasculature, the pH does not play a major role in the development of tolerance and postinfusional hypotension. It is concluded that the heart is the primary site for the development of tolerance and postinfusional hypotension seen with these infusions of NE.