Synergistic effect of captopril and dobutamine on left ventricular pressure-volume and pressure-shortening relations in severe cardiac failure.

The acute effects of captopril and dobutamine, alone and in combination, on left ventricular contractility were assessed from left ventricular end-systolic pressure-volume and pressure-shortening relations in 6 patients with severe end-stage cardiac failure. Dobutamine was given by constant intravenous infusion on two occasions 48 hours apart, on one of these occasions the patient also received oral captopril in a dose of 37 +/- 12 mg 6-hourly. Pressures and cardiac index were measured, and left ventricular volumes and ejection fraction computed from simultaneously recorded radionuclide ventriculography. Dobutamine alone did not cause a statistically significant increase in stroke index, stroke work index, cardiac index and ejection fraction, although pulmonary capillary wedge pressure and right atrial pressure fell (P less than 0.05). There was no change in systemic or pulmonary vascular resistance nor in arterial blood pressure. Following administration of captopril, diastolic arterial pressure decreased (P less than 0.05), and the dobutamine challenge produced a greater and significant rise in stroke and stroke work index (P less than 0.05) and cardiac index (P less than 0.01). The left ventricular contractile state was unaltered by captopril but appeared to increase with dobutamine and more so during combined therapy with captopril and dobutamine, indicating a synergistic effect of the two drugs when given in combination.

Effect of captopril on left ventricular end-systolic pressure-volume and stress-shortening relations in severe cardiac failure.

The effects of captopril on cardiovascular dynamics and left ventricular (LV) contractility were studied in 11 patients with severe congestive heart failure and very poor global LV function. Pressures were measured using a flow-guided catheter, cardiac output by thermodilution, and LV contraction and ejection fraction by simultaneous radionuclide angiography. Ventricular loading conditions were altered by sublingual isosorbide dinitrate to facilitate construction of LV pressure-volume and stress-shortening curves. Captopril decreased mean arterial pressure (p less than 0.02) and systemic vascular resistance, while stroke and cardiac index increased in most patients. Left ventricular ejection fraction increased from 18 +/- 5 to 22 +/- 7% (p less than 0.05), but contractility, assessed from end-systolic pressure-volume and end-systolic pressure-shortening relations, was unchanged or decreased slightly. Heart rate and double product also tended to decrease. In contrast, arteriovenous oxygen difference widened and calculated total oxygen consumption increased during captopril therapy (p less than 0.05). The study showed that captopril improved forward blood flow, total oxygen extraction, and LV ejection fraction following the decrease impedance to LV emptying but not at the expense of an increase in ventricular contractility. This makes captopril an attractive drug for patients with end-stage cardiac failure and a severely damaged myocardium.

Chronotropic effect of hydralazine and its mechanism of symptomatic sinus bradycardia.

The positive chronotropic effect of hydralazine was studied in 9 patients with symptomatic sinus bradycardia. Hydralazine was given in an intravenous dose of 0.15 mg/kg and heart rate, blood pressure, sinoatrial conduction time (Narula method) and corrected sinus node recovery time were measured. The effect of hydralazine was also studied after total autonomic nervous system blockade using 0.04 mg/kg of atropine and 0.2 mg/kg of propranolol intravenously. In the control state hydralazine produced an increase of 28 +/- 15% (mean +/- standard deviation) in heart rate, and this was essentially due to a decrease in sinoatrial conduction time (by 32 +/- 32%, p less than 0.05). Corrected sinus node recovery time also tended to shorten (decrease of 21 +/- 34%, difference not significant). After total autonomic blockade intrinsic heart rate did not change or increased very little (9 +/- 14%) after administration of hydralazine and there was no consistent change in sinoatrial conduction and corrected sinus node recovery times. The small residual effect of hydralazine on heart rate was related to incomplete autonomic blockade, since the effect of postural change (standing) on heart rate was also not totally abolished. The study showed that the positive chronotropic effect of hydralazine was mainly due to a change in sinoatrial conduction with a smaller change in corrected sinus node recovery time, and the major chronotropic effect of the drug was mediated by the autonomic nervous system.