IMPROVEMENT IN EXERCISE-INDUCED LEFT-VENTRICULAR DYSFUNCTION BY INFUSION OF ALPHA-HUMAN ATRIAL-NATRIURETIC-PEPTIDE IN CORONARY-ARTERY DISEASE

The effects of recombinant or-human atrial natriuretic peptide (alpha-hANP) infusion on acute left ventricular dysfunction provoked by men with coronary artery disease. Patients performed symptom-limited, graded exercise on a supine bicycle ergometer. Plasma alpha-hANP and guanosine 3',5'-monophosphate (cyclic GMP) concentrations as well as hemodynamic variables were measured at rest, during and after exercise. In 14 patients whose pulmonary artery wedge pressure was >20 mm Hg at peak exercise, the same exercise protocol was repeated at 30 minutes after starting intravenous alpha-hANP infusion (0.05 mu g.kg(-1).min(-1)). In 8 of these patients, a Webster thermodilution catheter was advanced into the coronary sinus for measurement of coronary sinus blood flow. From the control exercise test, plasma alpha-hANP concentration increased from 86 +/- 20 pg/ml at rest to 188 +/- 32 pg/ml at peak exercise (p <0.001), and plasma cyclic GMP concentration increased from 4.8 +/- 1.9 pmol/ml at rest to 7.2 +/- 2.9 pmol/ml at peak exercise (p <0.001). Both plasma alpha-hANP and cyclic GMP concentrations showed a significant positive correlation with pulmonary artery wedge pressure during control exercise. With (alpha-hANP infusion, systolic and diastolic pulmonary artery pressures and pulmonary artery wedge pressure were significantly decreased at all time points during exercise testing. Heart rate was increased and systolic blood pressure was significantly decreased at rest and at 3 minutes of exercise. Diastolic blood pressure, mean blood pressure, systemic vascular resistance, and pulmonary vascular resistance were significantly decreased at rest. Thus, exercise-induced acute left ventricular dysfunction was improved in patients with coronary artery disease by intravenous alpha-hANP infusion, mainly through preload reduction without an apparent effect on coronary circulation.