CARDIOVASCULAR CONSEQUENCES OF CORRECTION OF THE ANEMIA OF RENAL-FAILURE WITH ERYTHROPOIETIN

The purpose of this study was to define the physiologic responses of the heart and peripheral circulation to chronic anemia using noninvasive measurements while eliminating confounding biochemical, pharmacologic and physiologic variables. Stable chronic hemodialysis patients were studied at the University Hospital based chronic dialysis unit and echocardiography laboratory before and after therapy with human recombinant erythropoietin (rHuEPO). Subjects included maintenance hemodialysis patients free of left ventricular regional wall motion abnormalities discernible by echocardiography, rhythm disturbance, significant valvular or ischemic heart disease. Two-dimensional echocardiograms and simultaneous targeted M-mode echocardiograms, phonocardiograms and externally acquired subclavian artery pulse tracings were used to measure whole blood viscosity, arterial blood gases and ionized calcium, complete blood count, electrolytes, creatinine, blood urea nitrogen (BUN), and inorganic phosphate. All measurements were made immediately post-dialysis before and after therapy with rHuEPO. The interval between pre- and post-rHuEPO studies was 8.3 +/- 2.3 months. We found that post-dialysis hematocrit rose from 24.7 +/- 0.9 to 36.4 +/- 0.9%, hemoglobin from 83 +/- 3 to 121 +/- 3 g/liter and whole blood viscosity from 2.87 +/- 0.11 to 3.71 +/- 0.18 centipoise (all, P < 0.001 after therapy with rHuEPO). The remaining biochemical measurements did not change. Heart rate fell from 83 +/- 3 to 77 +/- 3 beats/min (P = 0.013). Left ventricular preload and afterload were not statistically different before and after rHuEPO. Total vascular resistance rose from 1313 +/- 84 to 1568 +/- 129 dynes . sec . cm-5, P = 0.029. Cardiac output and cardiac index fell by 12 and 15% (P = 0.024 and 0.030), respectively. Left ventricular contractility assessed using load and heart rate independent indices fell after therapy with rHuEPO (P = 0.003) in the nine patients in whom it was measured. In conclusion, correction of the anemia of chronic renal failure in maintenance hemodialysis patients with rHuEPO reduces measurements of global left ventricular systolic function by decreasing the heart rate and contractile state without significantly altering chamber loading conditions. The net effect is a decrease in the hyperdynamic circulatory state that typically characterizes chronic anemia.