title: Effect of carvedilol on microcirculatory and glucose metabolic regulation in patients with congestive heart failure secondary to ischemic cardiomyopathy.
abstract: In a randomized (2:1), double-blinded design study, we studied 25 patients with congestive heart failure (66 +/- 9 years, ejection fraction 30 +/- 7%) before and after 23-week treatment with the beta blocker carvedilol 25 mg twice daily (n = 17) or placebo (n = 8) in addition to standard therapy. Using dynamic positron emission tomography, myocardial perfusion at rest and perfusion reserve after dipyridamole (0.56 mg/kg/min) were measured. Myocardial glucose uptake and plasma levels of catecholamines were also estimated. Carvedilol treatment reduced the rate-pressure product (8,781 +/- 2,672 vs 6,342 +/- 1,346, p <0.01) and improved ejection fraction (29 +/- 7% vs 37 +/- 11%, p <0.001), whereas no changes were observed in the control group. Perfusion at rest was unchanged in the placebo group (0.81 +/- 0.17 vs 0.86 +/- 0.23 ml/g/min, p = NS), whereas the carvedilol-treated group showed a significant reduction (0.88 +/- 0.26 vs 0.75 +/- 0.16 ml/g/min, p <0.05). Dipyridamole-induced hyperemia was significantly reduced after carvedilol treatment (1.51 +/- 0.45 vs 1.31 +/- 0.51 ml/g/min, p <0.001), whereas myocardial perfusion reserve was unaltered. Carvedilol did not alter myocardial glucose uptake (0.33 +/- 0.14 vs 0.32 +/- 0.12 micromol/g/min, p = NS) or the plasma catecholamines levels. We therefore conclude that in patients with congestive heart failure, carvedilol reduced resting and hyperemic perfusion. No effect on glucose uptake or catecholamine levels was observed. The reduced perfusion at rest must reflect reduced perfusion demand and thereby a higher threshold for myocardial ischemia and protection against myocardial damage or malignant arrhythmia. These effects may serve as a pathophysiologic explanation for the reduced mortality in patients with congestive heart failure who receive carvedilol.
authors.affiliation: Department of Cardiology B, Skejby Sygehus, Aarhus University Hospital, Aarhus, Denmark. mboe@dadlnet.dk
authors.forename: Morten
authors.initials: M
authors.lastname: Bøttcher
authors.forename: Jens
authors.initials: J
authors.lastname: Refsgaard
authors.forename: Ole
authors.initials: O
authors.lastname: Gøtzsche
authors.forename: Frederik
authors.initials: F
authors.lastname: Andreasen
authors.forename: Torsten Toftegaard
authors.initials: TT
authors.lastname: Nielsen
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002395:Catecholamines / Q000097:blood; D003331:Coronary Vessels / Q000187:drug effects; D004176:Dipyridamole / Q000008:administration & dosage; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications; D011412:Propanolamines / Q000627:therapeutic use*; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D002227:Carbazoles; D002395:Catecholamines; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D004176:Dipyridamole