Effects of diltiazem (Dil) on cardiac function were studied in the anesthetized open chest and heart-lung preparation of dogs. In the anesthetized dog, Dil (0.03-0.3 mg/kg, i.v.) increased max dp/dt and raised left ventricular end-diastolic pressure (LVEDP). Dil also produced an increase in cardiac output and coronary blood flow, but produced a decrease in blood pressure and heart rate (HR). In the cardiac denervated dog (bilateral stellectomy and vagotomy), the increase in max dp/dt caused by Dil, although not so remarkable was apparent. Therefore, the effects of Dil on cardiac function were examined in the heart-lung preparations of the dog, in which arterial pressure (AP) and venous pressure (VP) were kept constant (spontaneously beating) or AP, VP and HR were kept constant (atrial pacing). In these preparations Dil (about 1 mg/l) decreased max dp/dt and raised LVEDP. The cardiac function curve (relationship between stroke work and LVEDP) was shifted rightward by Dil. On the other hand, max dp/dt was increased when VP was increased under constant AP and HR. This increase in max dp/dt was also found under the influence of Dil. These results suggest that the augmentation of max dp/dt induced by Dil in the open chest dog is due both to a neural reflex in response to the systemic hypotension and to the Starling mechanism produced by increase in venous return, though Dil itself has a negative inotropic property.
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