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1 Department of Pharmacology, Harvard Medical School, Boston, Massachusetts
In the heart-lung preparation of the dog the heart rate increase caused by 400 mg of calcium chloride was similar to that produced by the infusion of 3 µg/minute of norepinephrine. Sodium pentobarbital had a greater rate-decreasing action when the rate was increased by calcium than when it was raised by norepinephrine.
In isolated, spontaneously beating guinea-pig atria, suspended in a bicarbonate buffered physiological solution at 37°C, changes in the external calcium concentrations had characteristic effects on the rate. Increasing the calcium concentration from 0.62 to 15 mM led to a progressive change in heart rate. There was first an increase in rate reaching a maximum at 5 to 10 mM; at higher calcium concentrations atrial rate declined again. Pretreatment with reserpine (3 mg/kg, 24 hours) did not abolish this positive chronotropic effect but enhanced it.
When sodium pentobarbital was given in cumulative doses to atria kept during the whole experiment at the same calcium concentration, the negative chronotropic effect of calcium was the greater the higher the calcium concentration. At concentrations below 5 mM, calcium augmented the rate-decreasing effect of sodium pentobarbital, but not more than would be expected on the basis of the higher atrial rate. At concentrations above 5 mM, calcium greatly enhanced the negative chronotropic action of sodium pentobarbital.
Accepted on June 2, 1964