Abstract
IntroductionAging is associated with a decline in cardiac contractility and altered immune function. The aim of this study was to determine whether aging alters endotoxin-induced myocardial dysfunction.MethodsSenescent (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.ResultsLPS (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.ConclusionLow 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.
Highlights
Aging is associated with a decline in cardiac contractility and altered immune function
Ca2+ myofilament responsiveness, which is typically reduced in myocardium of young adult septic rats, was unaltered in senescent rats
Septic myocardial dysfunction may be altered with aging in its severity, mediators, and/or main cellular mechanisms
Summary
Aging is associated with a decline in cardiac contractility and altered immune function. Impairment in cardiac function is one of the most recognized organ dysfunctions in sepsis. The mechanism of myocardial dysfunction is complex and remains incompletely defined, increasing experimental evidence suggests that the main subcellular mechanisms include decreased cardiac myofilament responsiveness, nitric oxide (NO)-peroxynitrite activation, and inhibition of mitochondrial oxidative phosphorylation [1]. A senescent heart is characterized by a progressive decline in contractile function, with slowing of twitch contraction, altered Ca2+ handling kinetics, and impaired β-adrenergic modulation of contractility [2,3,4]. Aging is characterized by an altered immune function and response to stress, including endotoxic challenge [5]. Septic myocardial dysfunction may be altered with aging in its severity, mediators, and/or main cellular mechanisms
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