title: Heme oxygenase-1 and the ischemia-reperfusion injury in the rat heart.
abstract: Carbon monoxide (CO) is a signaling gas produced intracellularly by heme oxygenase (HO) enzymes using heme as a substrate. During heme breakdown, HO-1 and HO-2 release CO, biliverdin, and Fe(2+). In this study, we investigated the effects of manipulation of the HO-1 system in an in vivo model of focal ischemia-reperfusion (FIR) in the rat heart. Male Wistar albino rats, under general anesthesia and artificial ventilation, underwent thoracotomy, the pericardium was opened, and a silk suture was placed around the left descending coronary artery; ischemia was induced by tightening the suture and was monitored for 30 min. Subsequently, the ligature was released to allow reperfusion lasting for 60 min. The first group of rats was sham operated and injected intraperitoneally (i.p.) with saline. The second group underwent FIR. The third group was treated ip 18 hr before FIR with hemin (4 mg/kg). The fourth group was pretreated ip 24 hr before FIR and 6 hr before hemin with zinc protoporphyrin IX (ZnPP-IX, 50 microg/kg). Specimens of the left ventricle were taken for determination of HO expression and activity, infarct size, malonyldialdehyde (MDA) production, and tissue calcium content. FIR led to a significant increase in the generation of MDA and notably raised tissue calcium levels. Induction of HO-1 by hemin significantly decreased infarct size, incidence of reperfusion arrhythmias, MDA generation, and calcium overload induced by FIR. These effects were prevented by the HO-1 inhibitor ZnPP-IX. The present experiments show that the concerted actions of CO, iron, and biliverdin/bilirubin modulate the FIR-induced myocardial injury.
authors.affiliation: Departments of Preclinical and Clinical Pharmacology, University of Florence, 50139, Florence, Italy. emanuela.masini@unifi.it
authors.forename: Emanuela
authors.initials: E
authors.lastname: Masini
authors.forename: A
authors.initials: A
authors.lastname: Vannacci
authors.forename: C
authors.initials: C
authors.lastname: Marzocca
authors.forename: S
authors.initials: S
authors.lastname: Pierpaoli
authors.forename: L
authors.initials: L
authors.lastname: Giannini
authors.forename: O
authors.initials: O
authors.lastname: Fantappié
authors.forename: R
authors.initials: R
authors.lastname: Mazzanti
authors.forename: P F
authors.initials: PF
authors.lastname: Mannaioni
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011524:Protoporphyrins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
chemical_list: D011524:Protoporphyrins; C017803:zinc protoporphyrin; D008315:Malondialdehyde; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D002118:Calcium