title: Different preconditioning stimuli invoke disparate electromechanical and energetic responses to global ischemia in rat hearts.
abstract: One hypothesized mechanism of the cardioprotection provided by preconditioning is decreased utilization of ATP during ischemia. Although ATP levels in preconditioned heart during ischemia have been previously studied, contractile activity during ischemia has not been investigated. Contractile activity accounts for significant ATP consumption during ischemia. We hypothesized that preconditioning stimuli may conserve energy during the ischemic period by decreasing myocardial contractile energy expenditure prior to asystolic cardiac arrest. We studied three preconditioning stimuli: (i) four cycles of 5-min periods of ischemia (4 x 5' CI), (ii) 2 min of alpha 1-adrenergic stimulation (phenylephrine; PE), and (iii) 2 min of P1-purinergic stimulation (adenosine). The effects of these stimuli on myocardial ATP, ventricular contractility, and the time to cessation of electromechanical function (asystole) during the sustained ischemic period were then examined. Preconditioning stimuli (4 x 5' CI, phenylephrine, and adenosine) improved postischemic functional recovery compared with nonpreconditioned controls. Myocardial ATP contents at the end of 20 min of global ischemia were higher for adenosine-treated (9.0 +/- 1.5 mumol/g dry weight; p < 0.05) and PE-treated (9.9 +/- 1.9 mumol/g dryweight; p < 0.05) hearts than for controls (6.6 +/- 1.2 mumol/g dry weight). The CI hearts began with lower myocardial ATP levels (9.9 +/- 1.2 mumol/g dry weight; p < 0.05) than other groups prior to the sustained ischemic period (control 13.4 +/- 1.0 mumol/g dry weight). As a result of a lower rate of ATP depletion, ATP levels in the CI group were similar to the untreated control after 20 min of sustained ischemia (5.5 +/- 0.7 mumol/g dry weight). Preconditioning with 4 x 5' CI or adenosine (but not PE) led to earlier ventricular arrest. Only adenosine-treated hearts demonstrated a more rapid decline in ventricular contractility during sustained ischemia than did nonpreconditioned control hearts. We conclude that while the final recovery of ventricular contractility after asystolic arrest and reperfusion is improved by preconditioning with different stimuli (4 x 5' CI, adenosine, or PE), each stimulus conferred a characteristic electromechanical and energy conservation strategy during sustained ischemia. Adenosine conserved myocardial ATP content and reduced total cardiac work (developed pressure and heart beats). CI conserved myocardial ATP and minimized the number of ischemic cardiac beats. PE preserved myocardial ATP during ischemia without changing contractile behavior. Thus, energy conservation strategies during ischemia could contribute to the protection afforded by preconditioning stimuli, but the mechanisms appear to differ among stimuli.
authors.affiliation: Department of Surgery, University of Colorado, Denver 80262, USA.
authors.forename: T F
authors.initials: TF
authors.lastname: Rehring
authors.forename: P R
authors.initials: PR
authors.lastname: Bender
authors.forename: C B
authors.initials: CB
authors.lastname: Cairns
authors.forename: K
authors.initials: K
authors.lastname: Joo
authors.forename: R S
authors.initials: RS
authors.lastname: Friese
authors.forename: J I
authors.initials: JI
authors.lastname: Shapiro
authors.forename: J C
authors.initials: JC
authors.lastname: Cleveland
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002316:Cardiotonic Agents; D010656:Phenylephrine; D000255:Adenosine Triphosphate; D000241:Adenosine