Interactions of ketamine with vasoactive amines at normothermia and hypothermia in the isolated rabbit heart

Ketamine has been demonstrated to inhibit norepinephrine uptake in the adrenergic neuronal membrane, an action similar to that of cocaine. This study evaluated possible potentiation of five vasoactive amines, norepinephrine, epinephrine, tyramine, dopamine, and isoproterenol, by ketamine in the isolated rabbit heart at 35, 30, 25 and 20 C. The hearts were perfused with one of the vasoactive amines alone, ketamine (500 μg/ml) alone, and combinations of ketamine with the amines, in random order. Heart rate, left ventricular dP/dt, and left ventricular systolic, diastolic, and mean pressures were recorded. Heart rate was decreased by ketamine alone; this effect became less significant with increasing hypothermia. No significant change from control was observed at 25 or 20 C. Heart rate increased significantly during perfusion with ketamine plus norepinephrine, epinephrine, or tyramine compared with control, and during perfusion with these amines alone at 35 C. The potentiation of heart rate caused by ketamine plus norepinephrine compared with norepinephrine alone was not affected by cooling to any temperature, while the difference between extents of potentiation by epinephrine or tyramine with and without ketamine decreased with cooling, becoming insignificant at 25 C or less. Dopamine and isoproterenol produced greater increases of heart rate alone than when perfused with ketamine, the differences becoming less with cooling. Left ventricular dP/dt was significantly decreased by ketamine alone, this effect becoming less apparent with cooling. Ketamine combined with norepinephrine, epinephrine, tyramine, isoproterenol, or dopamine significantly increased dP/dt over control, while only ketamine combined with norepinephrine, epinephrine, and tyramine significantly increased dP/dt compared with these vasoactive amines alone. Potentiation of left ventricular dP/dt by ketamine plus epinephrine or tyramine (compared with these amines alone) became less apparent with cooling. When ketamine was combined with norepinephrine, however, similar extents of potentiation were observed at all temperatures compared with norepinephrine alone. Ketamine plus isoproterenol or dopamine decreased dP/dt compared with the amines alone at 35 C, this effect becoming less apparent with cooling. These results indicate that ketamine, like cocaine, may be a catecholamine uptake 1 inhibitor.