title: The protective effects of 17beta-estradiol against ischemia-reperfusion injury and its effect on pacing postconditioning protection to the heart.
abstract: The role of pacing postconditioning (PPC) in the heart protection against ischemia-reperfusion injury is not completely understood. The aim of this study was to investigated if 17-β-estradiol (estrogen, E2), endogenous atrial natriuretic peptide (ANP), endogenous brain natriuretic peptide (BNP), and tumor necrosis factor-alpha (TNF-α) are involved in PPC-mediated protection. Langendorff perfused female Wistar rat hearts were used for this study. Hearts challenged with regional ischemia for 30 min subjected to no further treatment served as a control. The PPC protocol was 3 cycles of 30 s pacing alternated between the right atrium and left ventricle (LV). Protection was assessed by recovery of LV contractility and coronary vascular-hemodynamics. Ischemia induced a significant (P < 0.05) deterioration in the heart function compared with baseline data. PPC alone or in combination with short-term E2 treatment (E2 infusion at the beginning of reperfusion) significantly (P < 0.05) improved the heart functions. Short-term E2 treatment post-ischemically afforded protection similar to that of PPC. However, long-term E2 substitution for 6 weeks completely attenuated the protective effects of PPC. Although no changes were noted in endogenous ANP levels, PPC significantly increased BNP expression level and decreased TNF-α in the cardiomyocyte lysate and coronary effluent compared to ischemia and controls. Our data suggested a protective role for short-term E2 treatment similar to that of PPC mediated by a pathway recruiting BNP and downregulating TNF-α. Our study further suggested a bad influence for long-term E2 substitution on the heart as it completely abrogated the protective effects of PPC.
authors.affiliation: Department of Physiology, Faculty of Medicine, Kuwait University, Jabria, Kuwait, fawzi.b@hsc.edu.kw.
authors.forename: Fawzi A
authors.initials: FA
authors.lastname: Babiker
authors.forename: Shaji
authors.initials: S
authors.lastname: Joseph
authors.forename: Jasbir
authors.initials: J
authors.lastname: Juggi
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003331:Coronary Vessels / Q000503:physiopathology; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D057775:Ischemic Postconditioning; D008297:Male; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D014409:Tumor Necrosis Factor-alpha; D020097:Natriuretic Peptide, Brain; D004958:Estradiol
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