title: A novel mechanism for myocardial stunning involving impaired Ca(2+) handling.
abstract: The mechanism of myocardial stunning has been studied extensively in rodents and is thought to involve a decrease in Ca(2+) responsiveness of the myofilaments, degradation of Troponin I (TnI), and no change in Ca(2+) handling. We studied the mechanism of stunning in isolated myocytes from chronically instrumented pigs. Myocytes were isolated from the ischemic (stunned) and nonischemic (normal) regions after 90-minute coronary stenosis followed by 60-minute reperfusion. Baseline myocyte contraction was reduced, P<0.01, in stunned myocytes (6.3+/-0.4%) compared with normal myocytes (8.8+/-0.4%). The time for 70% relaxation was prolonged, P<0.01, in stunned myocytes (131+/-8 ms) compared with normal myocytes (105+/-5 ms). The impaired contractile function was associated with decreased Ca(2+) transients (stunned, 0.33+/-0.04 versus normal, 0.49+/-0.05, P<0.01). Action potential measurements in stunned myocytes demonstrated a decrease in plateau potential without a change in resting membrane potential. These changes were associated with decreased L-type Ca(2+)-current density (stunned, -4.8+/-0.4 versus normal, -6.6+/-0.4 pA/pF, P<0.01). There were no differences in TnI, sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a), and phospholamban protein quantities. However, the fraction of phosphorylated phospholamban monomer was reduced in stunned myocardium. In rats, stunned myocytes demonstrated reduced systolic contraction but actually accelerated relaxation and no change in Ca(2+) transients. Thus, mechanisms of stunning in the pig are radically different from the widely held concepts derived from studies in rodents and involve impaired Ca(2+) handling and dephosphorylation of phospholamban, but not TnI degradation.
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, UMDNJ-New Jersey Medical School, Newark, NJ 07103-2714, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
authors.forename: R K
authors.initials: RK
authors.lastname: Kudej
authors.forename: A
authors.initials: A
authors.lastname: Yatani
authors.forename: Y K
authors.initials: YK
authors.lastname: Kim
authors.forename: G
authors.initials: G
authors.lastname: Takagi
authors.forename: R
authors.initials: R
authors.lastname: Honda
authors.forename: D A
authors.initials: DA
authors.lastname: Colantonio
authors.forename: J E
authors.initials: JE
authors.lastname: Van Eyk
authors.forename: D E
authors.initials: DE
authors.lastname: Vatner
authors.forename: R L
authors.initials: RL
authors.lastname: Rasmusson
authors.forename: S F
authors.initials: SF
authors.lastname: Vatner
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002469:Cell Separation; D004558:Electric Stimulation; D015151:Immunoblotting; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D009200:Myocardial Contraction; D017682:Myocardial Stunning / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013045:Species Specificity; D013552:Swine; D019210:Troponin I / Q000378:metabolism; D000099211:Phospholamban
chemical_list: D002118:Calcium; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D007527:Isoenzymes; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019210:Troponin I; D000099211:Phospholamban