Differing effects of metoprolol and propranolol on large vessel and microvessel responsiveness in a porcine model of coronary spasm.
OBJECTIVE
The purpose of this study is to assess the effect of beta1-selective blocker on coronary vasospasm.


METHODS
Balloon epicardial coronary artery endothelial denudation was performed at the left anterior descending coronary artery every 2 weeks for a total of 4 times in pigs. Changes in denuded site diameter and left anterior descending coronary artery blood flow caused by acetylcholine or serotonin were assessed before each endothelial denudation and at week 8 in untreated pigs (ED group) and in those treated with metoprolol (Meto group) or propranolol (Pro group).


RESULTS
In the ED group, decreased blood flow response to acetylcholine enhanced from -20+/-10% before the first ED to -100% (i.e. zero flow) at week 8 without denuded site narrowing, suggesting microvascular spasm, and serotonin-induced left anterior descending coronary artery diameter reduction at week 8 was -92+/-15%. In the Pro group, blood flow reduction by acetylcholine and left anterior descending coronary artery diameter reduction by serotonin did not change compared with those of the ED group. In the Meto group however, blood flow reduction by acetylcholine (week 8, -70+/-16%) and left anterior descending coronary artery diameter reduction by serotonin (week 8, -64+/-15%) were blunted (P<0.01) compared with those of ED and Pro groups.


CONCLUSIONS
The beta1-selective blocker metoprolol was effective to prevent coronary vasospasm.
Muto
Mitsuru
M
Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.
Saitoh
Shu-Ichi
S
Osugi
Taku
T
Matsumoto
Ken
K
Aikawa
Kazuhiko
K
Onogi
Futoshi
F
Ishibashi
Toshiyuki
T
Maruyama
Yukio
Y
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology; D017023:Coronary Angiography; D003329:Coronary Vasospasm / Q000378:metabolism / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D003683:Dehydroascorbic Acid / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D017078:Laser-Doppler Flowmetry; D008790:Metoprolol / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood; D011433:Propranolol / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D013552:Swine
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D018678:Cholinergic Agents; D018490:Serotonin Agents; D009569:Nitric Oxide; D012701:Serotonin; C000820:semidehydroascorbic acid; D011433:Propranolol; D008790:Metoprolol; D000109:Acetylcholine; D003683:Dehydroascorbic Acid