The effects on cardiac performance and systemic and coronary blood flow of rapid atrial pacing alone and associated with an intravenous infusion of a slow calcium channel inhibitor, diltiazem, at a dose of 20 mg/kg were studied in 20 patients with chronic coronary artery disease. Atrial pacing increased coronary flow and myocardial oxygen consumption: it decreased coronary arterial resistance and the coronary arteriovenous difference in lactates. Left ventricular end diastolic pressure rose significantly compared to the basal state in the period following pacing. The administration of diltiazem was associated with a significant fall of femoral arterial pressure, of coronary arteriovenous difference and myocardial consumption of oxygen, and an increase in the coronary arteriovenous difference in lactate. Left ventricular end diastolic pressure did not differ significantly from the basal values recorded after terminating atrial pacing. Left ventricular end diastolic volume decreased. Diltiazem opposed or cancelled the undesirable effects of rapid atrial pacing with respect to coronary arteriovenous difference in lactate content. The beneficial action of diltiazem does not seem to be closely related to its hemodynamic effects. It could be related to a reduction in myocardial oxygen demands due to a decrease in systolic ventricular strain and the specific metabolic effects of the drug, and also to an increase in myocardial oxygen supply due to the reduction in left ventricular end diastolic stress and the coronary vasodilation caused by the drug.

The effects of a single intravenous injection of dihydralazine (0.1 mg/kg) on coronary blood flow and myocardial metabolism were studied in 10 patients with primary congestive cardiomyopathy. Cardiac output and coronary blood flow increased significantly (p < 0,001 and p < 0,05); myocardial oxygen consumption, cardiac work and the coronary arteriovenous difference in lactates did not change significantly. However, the effects of dihydralazine are variable; coronary blood flow decreased in 2 patients; myocardial oxygen consumption increased in 3 patients; the coronary arteriovenous difference of lactate concentration fell or inversed in 5 patients. This data suggests that dihydralazine may have an undesirable effect on myocardial metabolism in some cases of congestive cardiomyopathy. Further long term studies are indicated to define the role of this drug in cardiac therapeutics.

The changes in the systemic and coronary circulations produced by intravenous trinitrin 0.38 +/- 0.125 mg/hour and sublingual isosorbide dinitrate 5 mg were studied in 24 patients with coronary artery disease. When given during rapid atrial pacing both drugs decreased pulmonary capillary pressures (p less than 0.001), cardiac and coronary output (p less than 0.001 and p less than 0.01) and myocardial oxygen consumption (p less than 0.01). At these dosages, intravenous trinitrin has no significant effect on average systemic blood pressure or left ventricular work index; the coronary arterial resistances increased (p less than 0.005). Isosorbide dinitrate significantly decreased average systemic blood pressure and the left ventricular work index (p less than 0.001); there was no significant difference in the coronary arterial resistances; the decrease in coronary blood flow observed after sublingual isosorbide dinitrate seems partly due to a decreased perfusion pressure. The beneficial effect of these nitrite derivatives seems to be mainly related to a reduced preload.

Intravenous infusion of trinitrin (0.38 +/- 0.25 mg/hour) during rapid atrial pacing reduced pulmonary capillary pressures, cardiac output, coronary blood flow and myocardial oxygen consumption. At these dosages trinitrin allows patients with ischaemic heart disease to undergo atrial pacing in the best conditions by maintaining the pulmonary capillary and systemic arterial pressures and myocardial lactate production within limits close to the basal values. The beneficial effects last during the recovery period after the termination of pacing and of the intravenous infusion.