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+/Ca2+ 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 β-adrenergic stimulation was greater in papillary muscles from TG than WT mice (WT, 13.2 ± 0.9; TG, 16.3 ± 1.0 mN/mm2 at 10−4 M isoproterenol). The sarcoplasmic reticulum (SR) Ca2+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 Ca2+ content via overexpression of the Na+/Ca2+ exchanger.