TY - JOUR T1 - BLOCKADE OF THE POSITIVE INOTROPIC ACTION OF NOREPINEPHRINE BY CARDIAC GLYCOSIDES IN THE DOG DURING HYPOTHERMIA JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 97 LP - 106 VL - 136 IS - 1 AU - Marion deV. Cotten AU - Theodore Cooper Y1 - 1962/04/01 UR - http://jpet.aspetjournals.org/content/136/1/97.abstract N2 - Lowering the body temperature of normal dogs modifies the contractile response of the heart to norepinephrine, and this modified response is in turn drastically influenced by the administration of a cardiac glycoside during hypothermia (28-30°). In contrast to the smooth increase in ventricular contractile force and subsequent return to control after injection of norepinephrine at normal body temperature, the contractile response to norepinephrine during hypothermia in dogs is characterized by a triphasic action. This triphasic response consists of an initial brief increase in force (first phase), a secondary brief decrease in force (second phase) and a final prolonged increase in force, after which the force gradually returns to control. These changes are dose-dependent both with respect to the magnitude of the contractile force changes in the three phases and with respect to the duration of the three phases. Administration of a cardiac glycoside to normal dogs during hypothermia significantly increased ventricular contractile force, hut the subsequent injection of graded doses of norepinephrine produced only depression of the heart as indicated by a reduction in contractile force and blood pressure and by a rise in left atrial pressure. The magnitude and duration of the depressant action produced by norepinephrine were dose-dependent. From the observations made, it appeared that cardiac glycosides blocked the positive inotropic response to norepinephrine when the glycoside was given during hypothermia, leaving unopposed the phase of depression characteristically interposed between two phases of cardiac stimulation in the absence of a glycoside. Rewarming digitalized dogs to 37° did not restore the positive inotropic response to norepinephrine, but the negative inotropic action disappeared as body temperature was increased to normal. Recooling caused a return of the negative, but not the positive, inotropic response to norepinephrine. A positive inotropic response to norepinephrine began to reappear some 7 to 9 hours after injection of ouabain, but full recovery was not achieved within 18 hours. Digitalization of normal euthermic dogs did not significantly alter the positive inotropic response to graded doses of norepinephrine given at 37°. Subsequent cooling of dogs to 28° after digitalization at 37° also did not result in blockade of positive inotropic action of norepinephrine. This is in marked contrast to the action of cardiac glycosides when administered to dogs during hypothermia. ER -