To investigate whether chronic heart failure (CHF) is associated with a general dysfunction of the haematopoietic compartment.
Bone marrow was obtained during coronary artery bypass graft surgery from 20 patients with CHF (age 67 +/- 6 years, 75% NYHA class >= III, LVEF 32 +/- 6%), and 20 age- and gender-matched control patients with normal cardiac function. CD34(+) haematopoietic progenitor cells were isolated and cultured with increasing doses of erythropoietin (0.02-10 IU/mL, EPO), myeloid growth factors or a mix of both. After 14 days, burst forming units erythroid (BFU-E), and granulocyte or monocyte colony forming units (CFU-G, CFU-M, respectively) were counted. Apoptosis and erythropoietin-receptor (EPO-R) density were quantified by flow cytometry. Throughout the EPO dose range, the CD34(+) cells from CHF patients produced a two-fold lower number of BFU-E colonies compared with controls (P = 0.02). The resistance to EPO was associated with markedly increased apoptosis during erythroid differentiation in CHF patients compared with controls [5.3% (2.9-8.1%) vs. 1.5% (0.8-3.4%), P = 0.01]. Erythropoietin-receptor expression was, however, comparable between CHF patients and controls and the anti-apoptotic cytokine interleukin-3 did not rescue erythropoiesis. In the myeloid cultures, the number of CFU-G and CFU-M colonies was also two-fold lower in CHF patients compared with controls (both P <0.01). In the mixed-culture assay, myelopoiesis and erythropoiesis were reduced to a similar magnitude in CHF patients. The impaired clonogenic potential was independently associated with clinical and biochemical severity of CHF, but not with the presence of anaemia.
Chronic heart failure is associated with profound and general bone marrow dysfunction, simultaneously affecting multiple haematopoietic lineages.
- Bone marrow
- Heart failure
- BLUNTED ERYTHROPOIETIN PRODUCTION
- TREATMENT OPTIONS
- CHRONIC DISEASE