Publication

Effects of Ivabradine and Metoprolol on Cardiac Angiogenesis and Endothelial Dysfunction in Rats With Heart Failure

Ulu, N., Henning, R. H., Goris, M., Schoeinaker, R. G. & van Gilst, W. H., Jan-2009, In : Journal of Cardiovascular Pharmacology. 53, 1, p. 9-17 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

Myocardial infarction (MI)-induced remodeling is associated with disturbed myocardial perfusion through vascular changes, such as reduced capillary density and endothelial dysfunction. Heart rate reduction (HRR) initiated immediately after MI stimulates angiogenesis and attenuates left ventricular dysfunction. We aimed to investigate the effects of long-term HRR on cardiac angiogenesis and endothelial function in a rat model of post-MI heart failure. Rats received early or late ivabradine or metoprolol for 12 or 9 weeks, respectively, and compared with untreated MI and sham animals 12 weeks after MI. Heart rate was measured in the conscious rat. MI resulted in an increased heart weight to body weight ratio, a decline in capillary density and a marked reduction in acetylcholine-induced relaxation. Early and late HRR by either ivabradine or metoprolol significantly increased capillary to myocyte ratio. Moreover, this ratio was significantly correlated to heart rate (r = -0.324 and P = 0.036). Neither early nor late chronic HRR prevented endothelial dysfunction, except a moderate improvement in late MI ivabradine group. In MI rats, HRR either by ivabradine or metoprolol treatment increases cardiac angiogenesis. Late HRR strategy was comparable to early HRR, suggesting that the beneficial effects are independent of the time of onset of therapy after MI.

Original languageEnglish
Pages (from-to)9-17
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume53
Issue number1
Publication statusPublished - Jan-2009

    Keywords

  • angiogenesis, endothelial dysfunction, heart rate, heart failure, myocardial infarction, LEFT-VENTRICULAR FUNCTION, MYOCARDIAL-INFARCTION, RATE REDUCTION, GROWTH-FACTOR, ISCHEMIC CARDIOMYOPATHY, OXIDATIVE STRESS, CORONARY RESERVE, THERAPY, STIMULATION, BLOCKADE

ID: 4847762