Hemodynamic comparison of dopexamine and nitroprusside at high and low doses in patients with coronary artery disease and impaired left ventricular function

Pure vasodilator drugs are currently the preferred agents for treatment of acute and chronic heart failure of all grades of severity. In contrast, the role of drugs that combine vasodilation with inotropic action remains highly controversial despite their several advantageous physiological actions and long therapeutic history in heart failure. We hypothesize that this uncertainty might be due first to subtle unfavorable hemodynamic effects not detectable by the relatively crude hemodynamic methods by which these agents are usually analyzed, particularly with regard to the quantification of afterload, and secondly to the narrow therapeutic range of these drugs, such that the dose administered is critical. We tested this hypothesis by comparing several refined hemodynamic measurements of dopexamine, an inotropic vasodilator, with a pure arteriovenous dilator (sodium nitroprusside, SNP) on left ventricular (LV) systolic and diastolic function, large arterial behavior, and coupling of the left ventricle to the arterial system at two dose levels in 35 patients with ischemic heart disease. The study protocol was a fixed order of 15-min infusions of saline, dopexamine 1 microg/kg/min, and dopexamine 3 + ++microg/kg/min, or saline, SNP 1 microg/kg/min, and SNP 3 microg/kg/min. Detailed hemodynamic observations were made at the end of each 15-min infusion period. Both drugs produced equivalent arterial vasodilation, as measured by the decrease in systemic vascular resistance index (SVRI), but dopexamine resulted in a significantly greater increase in cardiac index (CI). Myocardial contractility, assessed by several load-independent indexes, increased with dopexamine, as anticipated with an inotropic drug, but did not alter with SNP. Arterial compliance, a measure of the distensibility of large conduit arteries, was increased by SNP but not by dopexamine. Arterial wave reflection was increased by dopexamine, especially at high doses, but reduced by SNP. Increased arterial compliance and reduced wave reflection reduce LV afterload. SNP reduced preload, whereas dopexamine had no effect on this aspect of ventricular function. Vasodilator drugs and those which combine vasodilator and inotropy increase cardiac output (CO) and reduce SVR. Therapy with inotropic vasodilators has no effect on preload and does not reduce the dynamic components of ventricular afterload, although it does reduce its static components. These effects are dose dependent; there is less perturbation of afterload at lower doses. In contrast, vasodilator therapy reduces preload and both static and dynamic parts of afterload.