Effects of a combination of metoprolol and dazmegrel on myocardial infarct size in rats

Abstract

1 The effects ofacute pretreatment with metoprolol, dazmegrel and a combination of these two drugs has been examined on myocardial infarct size in rats. Ischaemic damage was assessed 4 h after coronary artery occlusion in anaesthetized rats and after 48 h of ischaemia in conscious rats. Infarct size was measured histochemically (by using periodic-acid-Schiff diastase reaction for glycogen) and by standard histological examination (haematoxylin and eosin stain). 2 There was some evidence of protection of the myocardium by metoprolol following 4 h of ischaemia (determined histologically) but this was not apparent 48 h after occlusion. 3 When given alone, dazmegrel had no significant effects on infarct size assessed by either method. A clear reduction in the extent of glycogen depletion and histological damage was observed with the combination of metoprolol and dazmegrel 48 h after the onset of ischaemia. This protection was seen to occur in the horizontal plane of the heart, preventing the extension of the infarct towards the posterior wall of the left ventricle and showing some salvage of the epicardial surfaces.

The role of β‐adrenergic receptors in the regulation of cardiac tolerance to ischemia/reperfusion. Why do β‐adrenergic receptor agonists and antagonists protect the heart?

“…It is possible that in the latter case, a 6‐h ischemia was too long. In a study performed in rats with CAO (4 and 48 h), it was shown that metoprolol (2 mg/kg) reduces the IS/LV ratio at a 4‐h occlusion by 50% but does not affect infarct size at a 48‐h CAO [54]. It is possible metoprolol delays the onset of ischemic necrosis but does not prevent it.…”