Cardiac anti-ischemic effect of metoprolol: role of beta-blockade within the ischemic region.
The distribution of metoprolol and atenolol into ischemic and nonischemic myocardium was studied in anesthetized dogs, pigs, and cats. The beta-blockers were administered intravenously after coronary artery occlusion. Metoprolol was found to be significantly more efficiently distributed to the ischemic myocardium than atenolol in all three species. To investigate the functional implications of this difference in tissue distribution, the anti-ischemic effects of the two beta-blockers were studied in the 2-h period following coronary artery occlusion in anesthetized cats, in which heart rate was kept at a constant level. In this model, metoprolol (0.3 mg.kg-1 + 0.15 mg.kg-1.h-1) was found to attenuate or delay the developing ischemic process. This is shown by its significant reduction of (a) the decline of CK activity in ischemic myocardium, (b) the ST elevation in a precordial ECG lead, and (c) the decrease of arterial pressure and cardiac output. In contrast to metoprolol, atenolol (0.3 mg.kg-1 + 0.15 mg.kg-1.h-1) caused no significant anti-ischemic effect in this cat model. The difference in the effectiveness of the two drugs can most probably be explained by their differential distribution in the ischemic heart. Furthermore, the anti-ischemic effect of metoprolol shows that the presence of a beta-blocker in ischemic left ventricular myocardium can favorably affect the early phase of developing infarction.
Ablad
B
B
Department of Pharmacology and Biochemistry, Hässle Cardiovascular Research Laboratories, Mölndal, Sweden.
Abrahamsson
T
T
Adler
G
G
Björkman
J A
JA
Bjurö
T
T
Ek
L
L
Ervik
M
M
Sjöquist
P O
PO
Sutherland
I
I
Svensson
L
L
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001262:Atenolol / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002415:Cats; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003402:Creatine Kinase / Q000378:metabolism; D004285:Dogs; D004562:Electrocardiography; D008790:Metoprolol / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D013045:Species Specificity; D013552:Swine
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D003402:Creatine Kinase; D008790:Metoprolol