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Biochem Biophys Res Commun. 2001 Feb 23;281(2):491-8.
Selective beta(1)-blockade improves cardiac bioenergetics and function and decreases neuroendocrine activation in rats during early postinfarct remodeling.

Omerovic E, Bollano E, Mobini R, Madhu B, Kujacic V, Soussi B, Hjalmarson A, Waagstein F.

Wallenberg and Lundberg Laboratories, Sahlgrenska University Hospital, 413 45, Goteborg, Sweden.

In spite of the solid evidence that beta-blockade reduces mortality and morbidity in congestive heart failure (CHF) this therapy continues to be underused in clinical praxis. The reason for this may lie in scarcity of knowledge about the mechanisms of beta-blockade action. The major aim of this study was to investigate in vivo whether selective beta(1)-blockade may improve cardiac energy metabolism in rats with myocardial infarction in early postinfarct remodeling phase. Myocardial infarction (MI) was induced in male Sprague-Dawley rats by ligation of the left coronary artery. Two different groups of rats were studied, rats with MI treated with metoprolol (5 mg/kg/h; n = 9) and rats with MI saline treated (n = 9). The treatment with metoprolol was given by subcutaneously implanted minipumps and was initiated at 3 days postinfarct and during the period of 4 weeks. All rats were investigated with noninvasive methods (31)P magnetic resonance spectroscopy (MRS) and transthoracic echocardiography 3 days after induction of MI and 4 weeks later. Phosphocreatine/ATP ratio was normalized after the treatment with metoprolol while it was 50% lower in the saline group (p < 0.001). In the metoprolol group stroke volume and ejection fraction increased while deceleration time of mitral early filling was longer (all p < 0.05). Left ventricular weight as well as volumes and dimensions were similar between the groups. Plasma levels of noradrenaline (p = 0.058), adrenaline (p < 0.01) and brain natriuretic peptide (p = 0.09) were lower in the metoprolol group. Selective beta(1)-blockade with high dose of metoprolol initiated in the early postinfarct phase improves myocardial energy metabolism and function and prevents overactivation of sympathetic system. The beneficial effect on myocardial bioenergetics may be an important mode of action of beta-blockers which contributes to the clinical benefits of the therapy in CHF. Copyright 2001 Academic Press.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11181074&dopt=Abstract




Analyst. 1998 Jul;123(7):1611-6.
Magnetic molecularly imprinted polymer beads for drug radioligand binding assay.

Ansell RJ, Mosbach K.

Department of Pure and Applied Biochemistry, University of Lund Chemical Centre, Sweden.

Molecularly imprinted polymer-magnetic iron oxide composite materials which exhibit recognition properties and can be withdrawn from solution by application of a magnetic field were prepared for the first time. Magnetic iron oxide was incorporated using a suspension polymerisation methodology with a perfluorocarbon liquid as the dispersing phase for the preparation of methacrylic acid-1,1,1-trimethylolpropane trimethacrylate copolymer beads molecularly imprinted with the beta-blocker (S)-propranolol. The resulting superparamagnetic imprinted polymer beads were capable of binding [3H]-(S)-propranolol more strongly than a non-imprinted, otherwise identical, polymer. In a competitive radioligand binding assay using a magnet to separate polymer from solution, (R)-propranolol and (R,S)-metoprolol exhibited cross-reactivities of 19 and 0.7%, respectively, compared with (S)-propranolol.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9830174&dopt=Abstract

hhp.ufl.edu

BACKGROUND: Chronotropic incompetence is one cause of diminished exercise capacity in heart transplant recipients. If reinnervation occurs, it often is late after transplantation and is not always accompanied by functional improvements in peak heart rate and appropriate tachycardia during exercise. To determine the efficacy of rate-responsive pacing on peak heart rate and exercise capacity, the authors studied eight male heart transplant recipients (age 57 +/- 12 years; 23 +/- 9 months after transplantation) that had either atrial or dual-chambered pacemakers. METHODS: All subjects completed two maximal graded exercise tests (GXT) using the Naughton treadmill protocol. During the first GXT, pacemakers were programmed for bradycardia support only and without rate responsiveness (unpaced). After a 14-day regimen of beta blockade with metoprolol to nullify the influence of circulating catecholamines on heart rate, subjects performed the second GXT with pacemakers programmed to respond optimally in the rate-responsive mode (paced). RESULTS: Peak heart rate (149 versus 129 bpm), peak oxygen uptake (18.9 versus 15.4 mL/kg/min), treadmill time to exhaustion (14.6 versus 12.4 min), and minute ventilation (76.7 versus 66.2 L/min) were significantly increased (P < or = 0.05) during the paced versus unpaced GXT. CONCLUSIONS: The results of this study demonstrate that chronotropic support of the transplanted heart using a rate-responsive pacemaker, with activity-based sensors programmed for maximal sensitivity, improves both peak heart rate and exercise capacity in heart transplant recipients significantly more than circulating catecholamines alone.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11144044&dopt=Abstract













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