title: Intravenous atenolol and esmolol maintain the protective effect of ischemic preconditioning in vivo.
abstract: Catecholamines bind to alpha- and beta-adrenoreceptors and are capable of preconditioning ischemic myocardium. Our purpose was to investigate the effect of acute either short or prolonged i.v. administration of beta-adrenoreceptor antagonists on ischemic preconditioning in vivo. Fifty-five anesthetized rabbits were divided into 10 groups (n=5-7 per group) and were subjected to 30-min regional ischemia of the heart after ligation of a prominent left coronary artery and 3-h reperfusion after releasing the snare. Ischemic preconditioning was obtained by three cycles of 5-min ischemia separated by 10-min reperfusion. beta-Adrenoreceptor blockade was obtained by the long acting beta-adrenoreceptor antagonist atenolol or by the short acting esmolol, which were given as a short 5-min infusion or as a prolonged 45-min infusion, starting respectively 20 min before and ending 15 min before the beginning of sustained ischemia, or starting 45 min before and ending immediately before the beginning of sustained ischemia. Atenolol was given at a rate of 0.2 mg min(-1) during 5 min or at a rate of 0.088 mg min(-1) as a 45-min infusion. Esmolol was given as an initial dose of 500 microg kg(-1) within 1 min, followed by a 4-min infusion at a rate of 50 microg kg(-1) min(-1) or as an initial dose of 3.4 mg within 1 min, followed by a 44-min infusion at a rate of 0.15 mg min(-1). Blood pressure and heart rate were continuously monitored. The infarcted and risk areas were delineated with the aid of tetrazolium chloride staining and fluorescent Zn-Cd particles. Infarct size was expressed in percent of the area at risk. All the animals without preconditioning developed an infarct size ranging between 36.3+/-2.4% and 49.6+/-7.6% (P=NS) and all the preconditioning groups developed an infarct size ranging between 14.9+/-1.2% and 21.0+/-2.2% (P=NS). All the preconditioning groups, independently of the use of beta-adrenoreceptor antagonists, had a smaller infarct size than the control group, which developed an infarct size of 47.3+/-2.5% (P<0.01). Intravenous atenolol and esmolol, independent of timing and mode of administration, does not seem to interfere with protection afforded by ischemic preconditioning in vivo.
authors.affiliation: 2nd Department of Cardiology, FESC, Onassis Cardiac Surgery Center, 356 Syngrou Ave, 176 74 Athens, Greece. elbee@ath.forthnet.gr
authors.forename: Efstathios K
authors.initials: EK
authors.lastname: Iliodromitis
authors.forename: Androniki
authors.initials: A
authors.lastname: Tasouli
authors.forename: Ioanna
authors.initials: I
authors.lastname: Andreadou
authors.forename: Elias
authors.initials: E
authors.lastname: Bofilis
authors.forename: Anastasia
authors.initials: A
authors.lastname: Zoga
authors.forename: Philip
authors.initials: P
authors.lastname: Cokkinos
authors.forename: Dimitrios Th
authors.initials: DT
authors.lastname: Kremastinos
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000401:mortality / Q000503:physiopathology; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D001262:Atenolol; C036604:esmolol