Myocyte-specific overexpression of NOS3 prevents endotoxin-induced myocardial dysfunction in mice

Abstract

Echocardiographic measurements were obtained before and 4 and 7 h after intraperitoneal challenge with endotoxin (Escherichia coli 0111:B4 lipopolysaccaride 50 mg/ kg) in wild-type C57BL6 mice (WT) and WT mice with myocyte-specific overexpression of NOS3 (TG), using a 13-MHz ultrasound probe (Sequoia, Acuson, Mountain View, CA). Invasive measurements of LV pressure and volume were obtained with a 1.4F pressure-volume catheter (SPR-839, Millar Instruments, Houston TX) (7 h after challenge with endotoxin or saline). At baseline, WT and TG mice had comparable measures of LV function. However, as assessed by echocardiography, the endotoxin-induced decrease in LV fractional shortening was attenuated in TG mice (from 54 ± 1 to 40 ± 1%) as compared to WT mice (from 56 ± 1 to 31 ± 2%). Invasive hemodynamics revealed that, compared to salinechallenged mice, dP/dtmax and cardiac output (CO) were markedly impaired in WT but not in TG 7 h after endotoxin challenge (Table 1).