Potential role of poly(ADP-ribose) activation in myocardial contractile dysfunction of human septic shock
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KeywordsSeptic Shock Severe Sepsis Peroxynitrite Septic Patient Myocardial Contractile
To study whether cardiodepression found in septic patients is associated with plasma markers of myocardial necrosis and with myocardial polyADP(ribose)polymerase (PARP) activation. Sepsis is associated with increased production of superoxide and nitric oxide with consequent peroxynitrite (ONOO-) generation. Cardiodepression is induced in the heart during oxidative stress associated with septic shock. Oxidative and nitrosative stress can lead to activation of the nuclear enzyme PARP, with subsequent loss of myocardial contractile function.
A prospective and observational study.
A university hospital ICU for clinical and surgical patients.
We assigned 25 patients presenting severe sepsis or septic shock.
Patients were followed for 28 days, and data were collected and analyzed a posteriori, separating into two groups: survivors and nonsurvivors.
Measurements and main results
Function of the heart in septic patients correlates to PARP activation in dead patients. The study population included 25 individuals, of whom 12 died during the follow-up period of 6 days. The initial data of inflammation marker C-reactive protein and APACHE severity were similar in both groups. Overall, an increase in the plasma troponin level was related to increased mortality risk. Patients that died presented heart dysfunction, and histological analysis of the heart showed inflammatory infiltration, increased collagen in the interstitium, and derangement of mitochondrial cryptae. Immunohistochemical staining for poly(ADP-ribose) (PAR), the product of activated PARP, was demonstrated in septic hearts. There was a positive correlation between PAR staining score and troponin I (r2 = 0.81); and a correlation of PAR staining score and LVSSW (r2 = 0.61).
Septic patients with impaired cardiac function demonstrate inflammatory alterations and PARP activation. We suggest that PARP activation may be, in part, responsible for the cardiac function depression observed in patients with severe sepsis.