Comparison of a beta-blocker and an If current inhibitor in rabbits with myocardial infarction.
OBJECTIVE
We compared protective effects of a ss-adrenoceptor blocker (metoprolol; Met) and a If current (Ivabradine; Iva) in a rabbit model of myocardial infarction.


METHODS
Experiments were performed on 44 adult New-Zealand-White (NZW) rabbits. The effects of either metoprolol or ivabradine were assessed 15 min after experimental occlusion of a coronary artery (CAO), 28 days after CAO (drug gavage), and in vitro hearts (Langendorff apparatus). The results were compared with sham and placebo hearts.


RESULTS
Metoprolol (0.25 mg/kg) slightly reduced heart rate and left ventricular systolic function. Ivabradine (0.25 mg/kg) reduced heart rate significantly (P<0.05) (18% vs control). Both drugs provided advantages over placebo: mortality was significantly (P<0.01)smaller (6/13 Pla animals died, 2/10 Met animals, and 3/11 Iva animals), left ventricular function was better preserved after 28 days (external power; Pla; Met; Iva=56%; 76%; 74%), and dilatation (BNP) was reduced (P<0.05). In the Pla group, the ST segment was significantly (P<0.05) elevated by 0.35 mV after CAO and exhibited in 50% of the animals Q waves after 28 days, while after ivabradine or metoprolol, ST displacement and Q waves had disappeared. The uneconomic myosin isoenzyme V3 predominated in Met hearts and Iva hearts (V3/V1: 63/37% and 62/38%), while it was further increased in Pla hearts (78/21%). External efficiency was lowest in Pla hearts (1.00+/-0.50 a.u.; P<0.05) and was significantly higher both in Met hearts (4.0+/-1.8 a.u.) and in Iva hearts (3.3+/-1.6 a.u.).


CONCLUSIONS
Met and Iva seem suited for the treatment of chronic myocardial infarction.
Langenbach
M R
MR
Department of Surgery, Helios Klinikum Wuppertal, University Witten/Herdecke, Germany. MRLangenbach@AOL.com
Schmitz-Spanke
S
S
Brockert
M
M
Schepan
M
M
Pomblum
V J
VJ
Gams
E
E
Zirngibl
H
H
Schipke
J D
JD
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001552:Benzazepines / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D000077550:Ivabradine; D008297:Male; D008790:Metoprolol / Q000494:pharmacology* / Q000627:therapeutic use; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D011817:Rabbits; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D024723:Ventricular Myosins / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D002316:Cardiotonic Agents; D026902:Potassium Channel Blockers; D020097:Natriuretic Peptide, Brain; D000077550:Ivabradine; D024723:Ventricular Myosins; D008790:Metoprolol