Beta-blockade in the ischemic reperfused working rabbit heart: dissociation of beta-adrenergic blocking and protective effects.
The cardioprotective effects of the beta-blocking drugs (dl-nebivolol, d-nebivolol, propranolol, atenolol, dilevalol and pindolol) were tested in the isolated working rabbit heart. The effects of l-nebivolol, having little beta-adrenoceptor blocking activity, were also studied. The hearts were subjected to 25 min ischemia, followed by 30 min of reperfusion. In solvent-treated hearts, ischemia resulted in a considerable loss of function. The mean functional recovery of one of the most sensitive parameters, i.e. aortic flow, was only 6%. Pretreatment either with dl-nebivolol, d-nebivolol, l-nebivolol or propranol significantly improved cardiodynamic function. Recovery after pretreatment with atenolol, dilevalol and pindolol (less than 10 mg/l) was not significantly improved when compared to solvent-treated hearts. The results suggest that the protective effects of some beta-blockers are most probably not related to beta-adrenoceptor blocking activity.
Lu
H R
HR
Department of Cardiovascular Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Vandeplassche
G
G
Wouters
L
L
Borgers
M
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D011817:Rabbits
D000319:Adrenergic beta-Antagonists; D007545:Isoproterenol