RELATIONSHIPS AMONG CARDIAC INOTROPIC RESPONSES TO NOREPINEPHRINE AND CARDIAC AND BLOOD CONCENTRATIONS OF H³-NOREPINEPHRINE DURING HYPOTHERMIA

¹ Department of Pharmacology, University of Oklahoma School of Medicine, Oklahoma City, Oklahoma

Infusin of small amounts of norepinephrine in the dog during hypothermia only increased myocardial contractile force. Infusion of larger amounts, however, caused a triphasic contractile force pattern characterized by an initial, brief increase, a decline to a stable level which persisted throughout the infusion and a substantial increase in force after the infusion was stopped. The decrease in force was proportional to the dose. Contractile force increased until estimated plasma concentrations reached 8 to 10 mµg/ml and decreased at higher concentrations. After ouabain was administered during hypothermia, norepinephrine only decreased contractile force. The force did not begin to decrease until the plasma concentration exceeded 10 mµg/ml, and returned to control only after the infusion was stopped and the plasma concentration had fallen below 10 mµg/ml. Plasma concentrations of H³-norepinephrine were significantly higher after ouabain, and the glycoside appeared to inhibit the uptake of H³-norepinephrine by the heart. The negative, but not the positive, inotropic response to norepinephrine during hypothermia was potentiated by cocaine, and dichloro-isoproterenol blocked both the positive and negative inotropic responses. Both the positive and negative inotropic responses appear to be beta in nature, but are apparently caused by independent processes since the positive inotropic response is blocked selectively by ouabain given during hypothermia.