Overexpression of Na+/Ca2+ exchanger gene attenuates postinfarction myocardial dysfunction.
We monitored myocardial function in postinfarcted wild-type (WT) and transgenic (TG) mouse hearts with overexpression of the cardiac Na(+)/Ca(2+) exchanger. Five weeks after infarction, cardiac function was better maintained in TG than WT mice [left ventricular (LV) systolic pressure: WT, 41 +/- 2; TG, 58 +/- 3 mmHg; P < 0.05; maximum rising rate of LV pressure (+dP/dt(max)): WT, 3,750 +/- 346; TG, 5,075 +/- 334 mmHg/s; P < 0.05]. The isometric contractile response to beta-adrenergic stimulation was greater in papillary muscles from TG than WT mice (WT, 13.2 +/- 0.9; TG, 16.3 +/- 1.0 mN/mm(2) at 10(-4) M isoproterenol). The sarcoplasmic reticulum (SR) Ca(2+) content investigated by rapid cooling contractures in papillary muscles was greater in TG than WT mouse hearts. We conclude that myocardial function is better preserved in TG mice 5 wk after infarction, which results from enhanced SR Ca(2+) content via overexpression of the Na(+)/Ca(2+) exchanger.
Min
Jiang-Yong
JY
Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Sullivan
Matthew F
MF
Yan
Xinhua
X
Feng
Xin
X
Chu
Victor
V
Wang
Ju-Feng
JF
Amende
Ivo
I
Morgan
James P
JP
Philipson
Kenneth D
KD
Hampton
Thomas G
TG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004562:Electrocardiography; D015870:Gene Expression; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D006439:Hemodynamics / Q000187:drug effects / Q000235:genetics; D006579:Heterozygote; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000096:biosynthesis* / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control*
D000318:Adrenergic beta-Agonists; D019831:Sodium-Calcium Exchanger; D007545:Isoproterenol; D002118:Calcium