title: Altered excitation-contraction coupling in myocytes from remodeled myocardium after chronic myocardial infarction.
abstract: Following myocardial infarction (MI), the left ventricle undergoes progressive dilatation and eccentric hypertrophy, i.e., remodeling, which is greater in the adjacent than the remote region. The cellular mechanisms underlying these regional differences were studied. One (n=5) and 8 weeks (n=8) after anteroapical MI in sheep, cardiac myocytes were isolated from the adjacent and remote regions. At 8 weeks after MI, myocyte function in the remote region was not different from values either in sham controls (n=3) or animals 1 week after MI. At 8 weeks after MI, myocyte contractile function (% contraction) was decreased, P<0.01, in the adjacent region (6.4+/-0.4%), as compared with the remote region (8.8+/-0.5%) and was associated with decreased amplitude of Ca(2+)transients (adjacent, 0.69+/-0.09 v remote, 1.08+/-0.20, P<0.05) and L-type Ca(2+)current density (adjacent, 3.6+/-0.2 v remote, 4.8+/-0.2 pA/pF, P<0.05). Relaxation was also impaired significantly in myocytes from the adjacent region, associated with decreased protein levels of SERCA2a. The myocytes were hypertrophied more in the adjacent region than the remote region. Furthermore, focal areas of central myofibrillar lysis and increased glycogen deposition were observed in the adjacent region. These results indicate that impaired excitation-contraction coupling underlies dysfunction of myocytes from the adjacent non-infarcted myocardium after chronic MI, even in the absence of heart failure. Hypertrophy is implicated as the mechanism, since these changes were noted at 8 weeks, but not at 1 week after MI.
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Young-Kwon
authors.initials: YK
authors.lastname: Kim
authors.forename: Song-Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Kramer
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yatani
authors.forename: Gen
authors.initials: G
authors.lastname: Takagi
authors.forename: Sunil
authors.initials: S
authors.lastname: Mankad
authors.forename: Gyula P
authors.initials: GP
authors.lastname: Szigeti
authors.forename: Deepak
authors.initials: D
authors.lastname: Singh
authors.forename: Sanford P
authors.initials: SP
authors.lastname: Bishop
authors.forename: Richard P
authors.initials: RP
authors.lastname: Shannon
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Vatner
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Vatner
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002155:Calsequestrin / Q000378:metabolism; D004594:Electrophysiology; D006984:Hypertrophy; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012756:Sheep; D015398:Signal Transduction; D013997:Time Factors; D000099211:Phospholamban
chemical_list: D002118:Calcium; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002155:Calsequestrin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban