title: Ca2+ preconditioning elicits a unique protection against the Ca2+ paradox injury in rat heart. Role of adenosine. Fixed.
abstract: Repeated Ca2+ depletion and repletion of short duration, termed Ca2+ preconditioning (CPC), is hypothesized to protect the heart from lethal injury after exposing it to the Ca2+ paradox (Ca2+ PD). Hearts were preconditioned with five cycles of Ca2+ depletion (1 minute) and Ca2+ repletion (5 minutes). These hearts were then subjected to Ca2+ PD, ie, one cycle of Ca2+ depletion (10 minutes) and Ca2+ repletion (10 minutes). Hearts subject to the Ca2+ PD underwent rapid necrosis, and myocytes were severely injured. CPC hearts showed a remarkable preservation of cell structure; ie, 65% of the cells were normal in CPC hearts compared with 0% in the Ca2+ PD hearts. LDH release was significantly reduced in CPC hearts compared with Ca2+ PD hearts (2.45 +/- 0.18 and 8.02 +/- 0.7 U.min-1 x g-1, respectively). ATP contents of CPC hearts were less depleted compared with the Ca2+ PD hearts (5.9 +/- 0.8 and 3.0 +/- 0.16 mumol/g dry weight, respectively). Addition of the adenosine A1 receptor agonist R-phenylisopropyl adenosine before and during Ca2+ PD provided protection similar to that in CPC hearts, whereas the nonselective adenosine A1 receptor antagonist, 8-(p-sulfophenyl)-theophylline, blocked the beneficial effects of CPC. CPC-mediated protection was aborted when hearts subjected to CPC were treated with pertussis toxin (the guanine nucleotide or G-protein inhibitor). The present study suggests that Ca2+ preconditioning confers significant protection against the lethal injury of Ca2+ PD in rat hearts. Cardioprotection appears to result from adenosine release during preconditioning and by Gi-protein-modulated mechanisms.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Ohio.
authors.forename: M
authors.initials: M
authors.lastname: Ashraf
authors.forename: J
authors.initials: J
authors.lastname: Suleiman
authors.forename: M
authors.initials: M
authors.lastname: Ahmad
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D017682:Myocardial Stunning; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D010566:Virulence Factors, Bordetella; D010660:Phenylisopropyladenosine; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D037342:Pertussis Toxin; D000241:Adenosine; D002118:Calcium