Cardioprotection afforded by ischemic preconditioning interferes with chronic beta-blocker treatment.
OBJECTIVE
The efficacy of ischemic preconditioning of the heart has remained controversial. We investigated whether chronic treatment with beta-blockers affects the ischemic preconditioning in the isolated rat heart model.


METHODS
Wistar rats were treated with propranolol (50 mg/kg/day, p.o.) (PRL), with nipradilol (10 mg/kg/day, p.o.) (NPL), or with vehicle, for 4 weeks. Isolated rat hearts were divided into global ischemia hearts (GI, PRL and NPL, each n=6) and ischemic preconditioned hearts (IP, PRL+IP and NPL+IP, each n=6).


RESULTS
Significant differences in left ventricular pressure were observed between the PRL and PRL+IP, and between the NPL and NPL+IP groups. In the NPL group, significant amelioration and preservation of left ventricular peak pressure, coronary flow, reduction of infarct size, and NOx preservation were observed. Lipid peroxidation in the NPL group was significantly reduced before and after global ischemia compared to the GI group.


CONCLUSIONS
The effect of ischemic preconditioning was abolished in the hearts of rats following oral treatment of propranolol or nipradilol. However, the administration of nipradilol protected the ischemic and reperfused myocardium, partly due to the prevention of lipid peroxide formation.
Suematsu
Yoshihiro
Y
Department of Cardiac Surgery, Children's Hospital-Boston, Harvard Medical School, Boston, MA 02115, USA. yoshihiro.suematsu@childrens.harvard.edu
Anttila
Vesa
V
Takamoto
Shinichi
S
del Nido
Pedro
P
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D000075202:Contraindications; D006352:Heart Ventricles / Q000187:drug effects; D019194:Ischemic Preconditioning; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia; D015425:Myocardial Reperfusion; D009569:Nitric Oxide / Q000097:blood; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012449:Safety
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D009569:Nitric Oxide; D011433:Propranolol; C036089:nipradilol