Effect of D600, practolol, and alterations in magnesium on ionized calcium concentration-response relationships in the intact dog heart.

The effect of practolol, D600, and alterations in ionized magnesium concentration on the cardiovascular pharmacology of calcium was examined in vivo in the open-chest dog. In the presence of practolol the ionized calcium-dP/dt (first derivative of left ventricular pressure) concentration-response curve was shifted to the right, with a decreased slope and maximum. Practolol also shifted ionized calcium-S a T, (S wave to peak of T wave on ECG) relationships to the right but in a parallel fashion. Compound D600 produced a parallel shift to the right of ionized calcium-dP/dt relationships but only at maximal doses (0.80 mg/kg). In the presence of practolol, 2.5 mg/kg, D600 shifted ionized calcium-dP/dt relationships to the right at doses (0.8 and 0.25 mg/kg) that had no effect in the absence of practolol. Ionized calcium-dP/dt relationships were the same before and after chelation with EGTA, in contrast to results of the same experiment performed with sodium citrate as the complexing agent. In the intact canine heart, practolol appears to act as a noncompetitive antagonist, D600 as a competitive antagonist, and ionized magnesium as an antagonist of the effects of ionized calcium on dP/dt. D600 in doses of 0.25 mg/kg and 0.80 mg/kg produced hyperglycemia, and this effect was prevented by prior administration of practolol.