ABSTRACT
Title
Attenuation of lung protein synthesis in patients with chronic heart failure on beta-blocker therapy
Authors
M. Verri1, R. Aquilani2, A.I. Bongiorno1, M. Dossena1, M.T. La Rovere3 and O. Pastoris1.
1Dept. of Legal Medicine, Forensic and Pharmacotoxicological Sciences “A. Fornari”-Section of Pharmacological and Toxicological Sciences, University of Pavia, Italy; 2 Service of Metabolic and Nutritional Pathophysiology, 3 Dept. of Cardiology, “S. Maugeri” Foundation, IRCCS-Scientific Institute of Montescano (PV), Italy
1Dept. of Legal Medicine, Forensic and Pharmacotoxicological Sciences “A. Fornari”-Section of Pharmacological and Toxicological Sciences, University of Pavia, Italy; 2 Service of Metabolic and Nutritional Pathophysiology, 3 Dept. of Cardiology, “S. Maugeri” Foundation, IRCCS-Scientific Institute of Montescano (PV), Italy
Abstract
Background. In physiological conditions the pulmonary matrix undergoes continuous remodelling (Comper, 1996). Protein synthesis and oxidative metabolism are essential for this process (Frey and Olson, 2003) and, therefore, the proteins in the lungs are in constant flux undergoing degradation and re-synthesis (Fisher, 1984). An increased rate of lung remodelling has been found in both experimental models (Townsley et al., 1999) and human studies (Delgado et al., 2005) of chronic heart failure (CHF). We investigated pulmonary protein and amino acid metabolism, the biochemical basis of the remodelling process, in individuals with CHF receiving or not receiving beta-blocker (BB) therapy. We hypothesised that the rate of lung protein synthesis could be attenuated by BBs since these drugs reduce pulmonary vessel hyper-responsiveness from sympathetic overflow (Lowes et al., 2002). Methods. Clinically stable rehabilitative CHF patients on a waiting list for heart transplantation, without metabolic diseases or liver/renal failure, with stable weight over the preceding 3 months underwent right heart catheterisation, and radial artery incannulation. Mixed central venous (V) and arterial (A) blood samples were drawn simultaneously to calculate the venous-arterial difference (V-A) of amino acids (pulmonary uptake/release), particularly of phenylalanine, as this amino acid is neither synthesised nor degraded in the lung. Results. Sixteen patients on BB therapy (bisoprolol, a β1-selective agent at the mean dose of 2.1±0.7 mg/day) and six not receiving BB were analysed. Both groups showed a net pulmonary protein synthesis [i.e. a positive value of phenylalanine (V-A) x cardiac index product] that was lower in patients on BB- than in those not receiving BB therapy (15 ± 22 versus 41 ± 50 µmol·min-1·m-2, p<0.01). Conclusions. Patients with CHF have increased rates of net pulmonary protein synthesis suggesting an increased rate of lung remodelling. However, the therapy with BB is associated with less lung metabolic abnormalities. The main message for clinical practice that can be derived from this study is the importance of maximising physician/patient compliance regarding beta-blocker use, in part in order to reduce complications in chronic heart failure patients after general or cardiothoracic surgery.
Comper (1996). In: Tissue function. Harwood Academic Publishers, vol 1.
Frey and Olson (2003). Annu Rev Physiol. 65: 45-79.
Fisher (1984). Environmental Health Perspectives 55: 149-158.
Townsley et al. (1999). J Appl Physiol. 87: 1823-30.
Delgado et al. (2005). Eur J Heart Fail. 7: 1011-6.
Lowes et al. (2002). N Engl J Med. 346: 1357-65.
Comper (1996). In: Tissue function. Harwood Academic Publishers, vol 1.
Frey and Olson (2003). Annu Rev Physiol. 65: 45-79.
Fisher (1984). Environmental Health Perspectives 55: 149-158.
Townsley et al. (1999). J Appl Physiol. 87: 1823-30.
Delgado et al. (2005). Eur J Heart Fail. 7: 1011-6.
Lowes et al. (2002). N Engl J Med. 346: 1357-65.