Skoda Afonso

Inhibition of Coronary Vasodilating Action of Dipyridamole and Adenosine by Aminophylline in the Dog

Experiments were performed to determine (1) whether intravenously administered aminophylline inhibits the coronary vasodilating effects of intravenous or intracoronary administration of dipyridamole or adenosine and (2) whether aminophylline locally administered in the coronary artery inhibits the vasodilating action of adenosine given intravenously or injected into the coronary artery. Coronary vasodilator responses to dipyridamole or adenosine were determined before and after administration of aminophylline. Intravenous aminophylline was found to inhibit coronary vasodilatation induced by intravenous or intracoronary dipyridamole or adenosine. After intravenous aminophylline, adenosine administered intravenously or into the coronary artery was 2.5 to 4 times less effective in inducing coronary vasodilatation. Aminophylline injected locally into the coronary artery was also effective in inhibiting coronary vasodilatation induced by intravenous and intracoronary adenosine. The mechanism of this inhibitory phenomenon has not been elucidated.

Indomethacin and the prostaglandin hypothesis of coronary blood flow regulation

1. Recent experimental data support the view that prostaglandins might be involved in autoregulation of coronary blood flow. Since indomethacin blocks prostaglandin synthesis, the present study was performed to determine whether indomethacin also inhibits coronary vasodilatation induced by hypoxia.

Coronary vasodilator responses to hypoxia before and after aminophylline

1. In previous studies adenosine has been postulated to be the mediator in coronary blood flow regulation and aminophylline was found to inhibit the coronary vasodilator action of adenosine. The present study was performed to determine whether aminophylline inhibits coronary vasodilatation induced by hypoxia.

Enhancement of Coronary Vasodilating Action of ATP and Adenosine by Lidoflazine

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.

Enhancement of Coronary Vasodilator Action of Adenosine Triphosphate by Dipyridamole

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.

The systemic and coronary hemodynamic effects of synthetic bradykinin.

Abstract 1. The systemic and coronary hemodynamic effects of bradykinin have been studied during its infusion into anesthetized dogs. 2. The administration of bradykinin is associated with decreased peripheral, pulmonary, and coronary vascular resistance, accompanied by systemic arterial hypotension. 3. Cardiac output increased, and coronary blood flow increased in those animals with a normal or low resting coronary flow and decreased in those with high resting coronary blood flow. 4. The depletion of catecholamine, through the administration of reserpine, does not change the response basically, although it is modified slightly.

SYSTEMIC AND CORONARY HEMODYNAMIC EFFECTS OF TRIMETHAPHAN CAMPHORSULFONATE (ARFONAD) IN THE DOG.

The acute systemic and coronary hemodynamic effects of Arfonad were determined in 10 intact anesthetized mongrel dogs. A sustained 35 per cent reduction in systemic arterial mean blood pressure was the end point of drug administration. The hemodynamic effects were consistent with peripheral pooling of blood, reduced central venous pressure and decreased cardiac work and coronary blood flow. The coronary sinus oxygen content decreased and cardiac efficiency was reduced. The results were basically similar to those obtained with longer acting ganglion blocking drugs.

LEFT VENTRICULAR HEAT PRODUCTION DURING INDUCED TACHYCARDIA IN THE INTACT DOG.

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.

Systemic and Coronary Hemdynamic Effects of Triamterene (2, 4, 7 Triamino-6-Phenyl Pteridine)∗†

Conclusions 1. The acute hemodynamic effects of oral administration of 300 mg of triamterene are reported in a series of 7 normotensive human subjects. 2. Administration of the agent was associated with a decrease in cardiac output, accompanied by a reduction in central venous pressure, insignificantly diminished left ventricular work, and an increase in peripheral vascular resistance. 3. Coronary blood flow was unchanged and myocardial oxygen consumption maintained at the control level whereas calculated cardiac efficiency was reduced.

The systemic and coronary hemodynamic effects of guanethidine.

Abstract 1. 1. Guanethidine was administered intravenously in a dose of 15 mg. per kilogram of body weight to a series of dogs, and hemodynamic studies were performed before and an average of 22 minutes after its administration. 2. 2. Subsequent to administration of guanethidine there was an increase in cardiac rate, hemoglobin, hematocrit, and mean arterial blood pressure in the systemic arteries, pulmonary artery, and right atrium, as well as an increase in cardiac output, coronary blood flow, and left ventricular oxygen consumption. 3. 3. The increase in systemic arterial blood pressure subsequent to the administration of guanethidine was blocked by immediate prior administration of phentolamine, and the elevated pressure which resulted from guanethidine was reduced by the administration of phentolamine. 4. 4. Pretreatment of the dog with reserpine prevented the hypertensive phase of guanethidine action, as well as the usual increase in cardiac output and body oxygen consumption. 5. 5. These results are compatible with an increased sympathetic-like action during the intermediate phase of guanethidine action, and suggest that this phase could be due to the release of catecholamines.