Endotoxin-induced myocardial dysfunction in senescent rats

Senescent (24 month) and young adult (3 month) male Wistar rats were treated with intravenous lipopolysaccharide (LPS) (0.5 mg/kg (senescent and young rats) or 5 mg/kg (young rats only)), or saline (senescent and young control groups). Twelve hours after injection, cardiac contractility (isolated perfused hearts), myofilament Ca2+ sensitivity (skinned fibers), left ventricular nitric oxide end-oxidation products (NOx and NO2) and markers of oxidative stress (thiobarbituric acid reactive species (TBARS) and antioxidant enzymes) were investigated.LPS (0.5 mg/kg) administration resulted in decreased contractility in senescent rats (left ventricular developed pressure (LVDP), 25 ± 4 vs 53 ± 4 mmHg/g heart weight in control; P < 0.05) of amplitude similar to that in young rats with LPS 5 mg/kg (LVDP, 48 ± 7 vs 100 ± 7 mmHg/g heart weight in control; P < 0.05). In contrast to young LPS rats (0.5 and 5 mg/kg LPS), myofilament Ca2+ sensitivity was unaltered in senescent LPS hearts. Myocardial NOx and NO2 were increased in a similar fashion by LPS in young (both LPS doses) and senescent rats. TBARS and antioxidant enzyme activities were unaltered by sepsis whatever the age of animals.Low dose of LPS induced a severe myocardial dysfunction in senescent rats. Ca2+ myofilament responsiveness, which is typically reduced in myocardium of young adult septic rats, however, was unaltered in senescent rats. If these results are confirmed in in vivo conditions, they may provide a cellular explanation for the divergent reports on ventricular diastolic function in septic shock. In addition, Ca2+-sensitizing agents may not be as effective in aged subjects as in younger subjects.Impairment in cardiac function is one of the most recognized organ dysfunctions in sepsis. Although the mechanism of myocardial dysfunction is complex and remains incompletely defined, increasing experimental evidence suggests that the main subcellular mechanisms include decreased cardiac myofilament responsivenes