Abstract
It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid) can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg−1 d−1) for 2 weeks. The lipopolysaccharide-challenged rats were treated on a daily basis with intraperitoneal injection of methylprednisolone (5 mg kg−1 d−1) for 2 weeks. Under conditions of anesthesia and open chest, we recorded left ventricular (LV) pressure and ascending aortic flow signals to calculate the maximal systolic elastance (Emax) and the theoretical maximum flow (Qmax), using the elastance-resistance model. Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Qmax has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in Emax associated with the increased Qmax in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased Emax, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Qmax, indicating that the drug may have normalized the LV internal resistance. In parallel, the benefits of methylprednisolone on the LV systolic pumping mechanics were associated with the reduced cardiac levels of negative inotropic molecules such as peroxynitrite, malondialdehyde, and high-mobility group box 1 protein. Based on these data, we suggested that low-dose methylprednisolone might prevent lipopolysaccharide-induced decline in cardiac intrinsic contractility and LV internal resistance, possibly through its ability to reduce the aforementioned myocardial depressant substances. However, since our results were obtained in anesthetized open-chest rats, extrapolation to what may occur in conscious intact animals should be done with caution.
Highlights
Inflammatory disorders such as allergies, asthma, autoimmune diseases, and sepsis are a major cause of illness and death (Cooper and Stroehla, 2003; Riedemann et al, 2003)
A prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure (Keh et al, 2003; Oppert et al, 2005)
We investigated whether low-dose MP therapy can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation
Summary
Inflammatory disorders such as allergies, asthma, autoimmune diseases, and sepsis are a major cause of illness and death (Cooper and Stroehla, 2003; Riedemann et al, 2003). Lipopolysaccharide (LPS), which is the major bioactive component of the cell membrane of gram-negative bacteria, may promote and amplify inflammatory responses, generating various cardiodepressive mediators (Garner et al, 2003; Carlson et al, 2005; Andreasen et al, 2008). In LPS-induced inflammation, an excessive and prolonged production of nitric oxide (NO) exerts adverse effects on the heart (Kleinert et al, 2004). Corticosteroids have been used in the treatment of severe sepsis and septic shock for more than 50 years (Annane et al, 2009). In 2003, Annane and Cavaillon have shown that a low-dose hydrocortisone can reverse the systemic inflammatory response in subjects secondary to an infection. A prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure (Keh et al, 2003; Oppert et al, 2005). MP therapy increases aortic stiffness, the question that remains unanswered is whether LPS-induced impaired cardiac function can be improved by MP therapy associated with the attenuation of cardiosuppressing mediators
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