Growth hormone-induced reduction of soluble apoptosis mediators is associated with reverse cardiac remodelling and improvement of exercise capacity in patients with idiopathic dilated cardiomyopathy.
OBJECTIVE
Recent experimental and clinical data indicate that abnormal inflammatory and apoptotic processes contribute to the progression of chronic heart failure (CHF). We sought to study the effects of growth hormone (GH) on circulating soluble apoptosis mediators, and to investigate whether these GH-induced anti-apoptotic effects are associated with the reduction of left ventricular (LV) volumes and attenuation of exercise intolerance in idiopathic dilated cardiomyopathy (IDC) patients.


METHODS
Plasma tumour necrosis factor-alpha (TNF-alpha), its soluble receptors sTNFRI and sTNFRII, and plasma apoptosis mediators soluble Fas (sFas) and sFas Ligand (sFAsL) were measured (enzyme-linked immunosorbent assay) in 12 IDC patients (NYHA III; LVEF: 24+/-2%) before and after a 3-month subcutaneous administration of GH 4 IU every other day (randomized, crossover design). Peak oxygen uptake (VO2max), as well as LV volume indices, wall thickness, and end-systolic wall stress (ESWS) were also determined at the same period.


RESULTS
Treatment with GH produced a significant reduction in plasma TNF-alpha (7.8+/-1.1 versus 5.5+/-0.9 pg/ml, P<0.02), sTNFRI (4.0+/-0.4 versus 3.3+/-0.3 ng/ml, P<0.05), sTNFRII (2.8+/-0.3 versus 2.4+/-0.2 ng/ml, P<0.05), sFas (4.7+/-0.7 versus 3.3+/-0.5 ng/ml, P<0.05) and sFasL (33.5+/-9.7 versus 20.2+/-6.2 pg/ml, P<0.01). A significant reduction in ESWS (841+/-62 versus 634+/-48 g/cm, P<0.01), LV end-systolic volume index (LVESVI, 128+/-12 versus 102+/-12 ml/m, P<0.001) and LV end-diastolic volume index (LVEDVI, 228+/-16 versus 200+/-18 ml/m, P<0.01) as well as a significant increase in VO2max (15.3+/-0.7 versus 17.1+/-0.9 ml/kg per min, P<0.01) were also observed in the patient population after GH administration. Significant correlations were found between the GH-induced decrease of sTNFRII and sFasL and respective reduction of LVESVI.


CONCLUSIONS
Growth hormone administration reduces circulating TNF system and soluble apoptosis mediators in patients with IDC. These GH-induced anti-apoptotic effects may be associated with the improvement in exercise capacity as well as with the reverse of LV remodelling in patients with CHF and IDC.
Parissis
John T
JT
Second Department of Cardiovascular Medicine, Onassis Cardiac Surgery Centre Athens, Greece. jparissis@yahoo.com
Adamopoulos
Stamatis
S
Karatzas
Dimitrios
D
Paraskevaidis
John
J
Livanis
Efthimios
E
Kremastinos
Dimitrios
D
D017209:Apoptosis / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000188:drug therapy*; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D017079:Exercise Tolerance / Q000187:drug effects*; D053222:Fas Ligand Protein; D005260:Female; D005500:Follow-Up Studies; D013006:Growth Hormone / Q000627:therapeutic use*; D006334:Heart Function Tests; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D016896:Treatment Outcome; D048069:Tumor Necrosis Factors / Q000097:blood
D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors; D013006:Growth Hormone