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It is well established that heart rate is a determinant of myocardial oxygen consumption. However, it has not been demonstrated that the increase of oxygen consumption at faster rates actually represents loss of energy, degraded as heat. Control measurements of systemic and coronary hemodynamic and metabolic parameters and left ventricular heat production (measured by a recently reported method) were obtained in 10 dogs. Tachycardia was then induced electrically and the same parameters redetermined. Significant increases occurred in coronary blood flow, cardiac metabolic rate of oxygen, and left ventricular heat production. The elevated myocardial oxygen consumption at higher rates is associated with increased heat production.

Lidoflazine, a newly developed coronary vasodilator, greatly enhances the coronary vasodilating action of adenosine and ATP. Experiments were designed to study the combined coronary vasodilating effects of adenosine and lidoflazine and to quantify the enhancement of coronary vasodilation of adenosine and ATP by prior administration of lidoflazine. Results of the experiments showed that the combined coronary vasodilating effects of adenosine and lidoflazine can be classified as supra-additive. For 3 hours after the administration of lidoflazine there was a great intensification (20 to 150 times) of the vasodilating action of adenosine or ATP. An adenosine-sparing effect of lidoflazine in whole blood was also demonstrated, and the enhancement of adenosine action is in part related to this effect. It is suggested that lidoflazine may also produce a change in the sensitivity of the smooth muscle of the coronary vessels to the direct or indirect action of adenosine.

It has been reported that previously administered dipyridamole intensifies the coronary vasodilator action of adenosine compounds. In the present study, a combination of dipyridamole and ATP at doses that alone are ineffective was examined for its effect on the coronary sinus blood flow. In 10 anesthetized dogs, heart rate, arterial blood pressure, cardiac output, and coronary sinus blood flow were measured before and during a 20-min constant-rate infusion of (a) ATP alone, 1 mg/min; (b) a combination of ATP, 1 mg/min, and dipyridamole, 0.005 mg/kg/min; and (c) dipyridamole alone, 0.005 mg/kg/ min. Coronary sinus flow was measured by a newly developed thermodilution flowmeter. Consistently during the infusion of ATP or dipyridamole alone no changes in the measured parameters occurred, whereas during infusion of the combination a very marked and sustained elevation (+493%) of coronary flow occurred, associated with a moderate increase in cardiac rate (+37%) and output (+42%) and a decrease in arterial blood pressure (-17%). In 7 other dogs, coronary vasodilator responses to ATP were determined before and 1 hour after a single 10-mg dose of dipyridamole. After dipyridamole, the coronary vasodilator action of ATP increased 5- to 100-fold. In a third group of 3 dogs, dipyridamole did not enhance the coronary vasodilator effects of nitroglycerin, bradykinin, or acetylcholine.

Hexamethonium bromide in normotensive and renal hypertensive dogs resulted in significant reductions in arterial blood pressure, cardiac output and cardiac work. The decrease in cardiac output relative to that in blood pressure suggests that the blood pressure reduction was largely due to the decrease in cardiac output. There was a decrease in coronary flow accompanied by an increase in myocardial oxygen extraction of such Degrees that cardiac oxygen consumption remained unchanged. Since myocardial oxygen consumption remained unchanged despite the decrease in cardiac work the calculated cardiac efficiency was decreased.