Potential role of poly(adenosine 5′-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock

Francisco G. Soriano, Antonio C. Nogueira, Elia G. Caldini, Marcelo H. Lins, Ana C. Teixeira, Sylas B. Cappi, Paulo A. Lotufo, Márcia M S Bernik, Zsuzsanna Zsengellér, Min Chen, Csaba Szabo

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Objective: Sepsis is associated with increased production of superoxide and nitric oxide, with consequent peroxynitrite 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 poly(adenosine 5′-diphosphate [ADP]-ribose) polymerase (PARP), with subsequent loss of myocardial contractile function. The aim of the study was to investigate whether cardiodepression found in septic patients is associated with plasma markers of myocardial necrosis and with myocardial PARP activation. Design: Prospective and observational study. Setting: University hospital intensive care unit for clinical and surgical patients. Patients: Twenty-five patients older than 18 yrs presenting with severe sepsis or septic shock. Patients with history of chronic heart failure, cancer, coronary artery disease, diabetes, or acquired immune deficiency syndrome were excluded. Interventions: Patients were followed for 28 days, and biochemical and hemodynamic data were collected on days 1, 3, and 6 of sepsis. The groups were survivors and nonsurvivors, defined only after the end of clinical patient evolution. Heart sections from patients who died were analyzed with hematoxylin-eosin and Picro Sirius-Red immunostaining and with electron microscopy. Measurements and Main Results: The study population included 25 individuals, of whom 12 (48%) died during the 6 days of follow-up. The initial data of the inflammation marker C-reactive protein and Acute Physiologic and Chronic Health. Evaluation severity were similar in both groups (nonsurvivors, 26 ± 2; survivors, 24 ± 5; NS). Overall, an increase in plasma troponin level was related to increased mortality risk. In patients who died, significant myocardial damage was detected, and histologie analysis of heart sections showed inflammatory infiltration, increased collagen deposition, and derangement of mitochondrial cristae. 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 densitometry and troponin I (r 2 = 0.73; p < .05), and the correlation of PAR staining densitometry and left ventricular systolic stroke work index was r 2 = 0.33 (p = .0509). Conclusion: There is significant PARP activation in the hearts of septic patients with impaired cardiac function. We hypothesize that PARP activation may be partly responsible for the cardiac depression seen in humans with severe sepsis.

Original languageEnglish (US)
Pages (from-to)1073-1079
Number of pages7
JournalCritical Care Medicine
Volume34
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Fingerprint

Poly Adenosine Diphosphate Ribose
Septic Shock
Sepsis
Densitometry
Staining and Labeling
Survivors
Oxidative Stress
Heart Neoplasms
Troponin
Peroxynitrous Acid
Enzyme Activation
Troponin I
Poly(ADP-ribose) Polymerases
Hematoxylin
Eosine Yellowish-(YS)
Superoxides
C-Reactive Protein
Observational Studies
Intensive Care Units
Coronary Artery Disease

Keywords

  • Heart dysfunction
  • Oxidative and nitrosative stress
  • Peroxynitrite
  • Poly(ADP-ribose) polymerase
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Potential role of poly(adenosine 5′-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock. / Soriano, Francisco G.; Nogueira, Antonio C.; Caldini, Elia G.; Lins, Marcelo H.; Teixeira, Ana C.; Cappi, Sylas B.; Lotufo, Paulo A.; Bernik, Márcia M S; Zsengellér, Zsuzsanna; Chen, Min; Szabo, Csaba.

In: Critical Care Medicine, Vol. 34, No. 4, 04.2006, p. 1073-1079.

Research output: Contribution to journalArticle

Soriano, Francisco G. ; Nogueira, Antonio C. ; Caldini, Elia G. ; Lins, Marcelo H. ; Teixeira, Ana C. ; Cappi, Sylas B. ; Lotufo, Paulo A. ; Bernik, Márcia M S ; Zsengellér, Zsuzsanna ; Chen, Min ; Szabo, Csaba. / Potential role of poly(adenosine 5′-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock. In: Critical Care Medicine. 2006 ; Vol. 34, No. 4. pp. 1073-1079.
@article{b24fd39c80eb4a7d921fca353232045b,
title = "Potential role of poly(adenosine 5′-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock",
abstract = "Objective: Sepsis is associated with increased production of superoxide and nitric oxide, with consequent peroxynitrite 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 poly(adenosine 5′-diphosphate [ADP]-ribose) polymerase (PARP), with subsequent loss of myocardial contractile function. The aim of the study was to investigate whether cardiodepression found in septic patients is associated with plasma markers of myocardial necrosis and with myocardial PARP activation. Design: Prospective and observational study. Setting: University hospital intensive care unit for clinical and surgical patients. Patients: Twenty-five patients older than 18 yrs presenting with severe sepsis or septic shock. Patients with history of chronic heart failure, cancer, coronary artery disease, diabetes, or acquired immune deficiency syndrome were excluded. Interventions: Patients were followed for 28 days, and biochemical and hemodynamic data were collected on days 1, 3, and 6 of sepsis. The groups were survivors and nonsurvivors, defined only after the end of clinical patient evolution. Heart sections from patients who died were analyzed with hematoxylin-eosin and Picro Sirius-Red immunostaining and with electron microscopy. Measurements and Main Results: The study population included 25 individuals, of whom 12 (48{\%}) died during the 6 days of follow-up. The initial data of the inflammation marker C-reactive protein and Acute Physiologic and Chronic Health. Evaluation severity were similar in both groups (nonsurvivors, 26 ± 2; survivors, 24 ± 5; NS). Overall, an increase in plasma troponin level was related to increased mortality risk. In patients who died, significant myocardial damage was detected, and histologie analysis of heart sections showed inflammatory infiltration, increased collagen deposition, and derangement of mitochondrial cristae. 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 densitometry and troponin I (r 2 = 0.73; p < .05), and the correlation of PAR staining densitometry and left ventricular systolic stroke work index was r 2 = 0.33 (p = .0509). Conclusion: There is significant PARP activation in the hearts of septic patients with impaired cardiac function. We hypothesize that PARP activation may be partly responsible for the cardiac depression seen in humans with severe sepsis.",
keywords = "Heart dysfunction, Oxidative and nitrosative stress, Peroxynitrite, Poly(ADP-ribose) polymerase, Sepsis",
author = "Soriano, {Francisco G.} and Nogueira, {Antonio C.} and Caldini, {Elia G.} and Lins, {Marcelo H.} and Teixeira, {Ana C.} and Cappi, {Sylas B.} and Lotufo, {Paulo A.} and Bernik, {M{\'a}rcia M S} and Zsuzsanna Zsengell{\'e}r and Min Chen and Csaba Szabo",
year = "2006",
month = "4",
doi = "10.1097/01.CCM.0000206470.47721.8D",
language = "English (US)",
volume = "34",
pages = "1073--1079",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Potential role of poly(adenosine 5′-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock

AU - Soriano, Francisco G.

AU - Nogueira, Antonio C.

AU - Caldini, Elia G.

AU - Lins, Marcelo H.

AU - Teixeira, Ana C.

AU - Cappi, Sylas B.

AU - Lotufo, Paulo A.

AU - Bernik, Márcia M S

AU - Zsengellér, Zsuzsanna

AU - Chen, Min

AU - Szabo, Csaba

PY - 2006/4

Y1 - 2006/4

N2 - Objective: Sepsis is associated with increased production of superoxide and nitric oxide, with consequent peroxynitrite 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 poly(adenosine 5′-diphosphate [ADP]-ribose) polymerase (PARP), with subsequent loss of myocardial contractile function. The aim of the study was to investigate whether cardiodepression found in septic patients is associated with plasma markers of myocardial necrosis and with myocardial PARP activation. Design: Prospective and observational study. Setting: University hospital intensive care unit for clinical and surgical patients. Patients: Twenty-five patients older than 18 yrs presenting with severe sepsis or septic shock. Patients with history of chronic heart failure, cancer, coronary artery disease, diabetes, or acquired immune deficiency syndrome were excluded. Interventions: Patients were followed for 28 days, and biochemical and hemodynamic data were collected on days 1, 3, and 6 of sepsis. The groups were survivors and nonsurvivors, defined only after the end of clinical patient evolution. Heart sections from patients who died were analyzed with hematoxylin-eosin and Picro Sirius-Red immunostaining and with electron microscopy. Measurements and Main Results: The study population included 25 individuals, of whom 12 (48%) died during the 6 days of follow-up. The initial data of the inflammation marker C-reactive protein and Acute Physiologic and Chronic Health. Evaluation severity were similar in both groups (nonsurvivors, 26 ± 2; survivors, 24 ± 5; NS). Overall, an increase in plasma troponin level was related to increased mortality risk. In patients who died, significant myocardial damage was detected, and histologie analysis of heart sections showed inflammatory infiltration, increased collagen deposition, and derangement of mitochondrial cristae. 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 densitometry and troponin I (r 2 = 0.73; p < .05), and the correlation of PAR staining densitometry and left ventricular systolic stroke work index was r 2 = 0.33 (p = .0509). Conclusion: There is significant PARP activation in the hearts of septic patients with impaired cardiac function. We hypothesize that PARP activation may be partly responsible for the cardiac depression seen in humans with severe sepsis.

AB - Objective: Sepsis is associated with increased production of superoxide and nitric oxide, with consequent peroxynitrite 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 poly(adenosine 5′-diphosphate [ADP]-ribose) polymerase (PARP), with subsequent loss of myocardial contractile function. The aim of the study was to investigate whether cardiodepression found in septic patients is associated with plasma markers of myocardial necrosis and with myocardial PARP activation. Design: Prospective and observational study. Setting: University hospital intensive care unit for clinical and surgical patients. Patients: Twenty-five patients older than 18 yrs presenting with severe sepsis or septic shock. Patients with history of chronic heart failure, cancer, coronary artery disease, diabetes, or acquired immune deficiency syndrome were excluded. Interventions: Patients were followed for 28 days, and biochemical and hemodynamic data were collected on days 1, 3, and 6 of sepsis. The groups were survivors and nonsurvivors, defined only after the end of clinical patient evolution. Heart sections from patients who died were analyzed with hematoxylin-eosin and Picro Sirius-Red immunostaining and with electron microscopy. Measurements and Main Results: The study population included 25 individuals, of whom 12 (48%) died during the 6 days of follow-up. The initial data of the inflammation marker C-reactive protein and Acute Physiologic and Chronic Health. Evaluation severity were similar in both groups (nonsurvivors, 26 ± 2; survivors, 24 ± 5; NS). Overall, an increase in plasma troponin level was related to increased mortality risk. In patients who died, significant myocardial damage was detected, and histologie analysis of heart sections showed inflammatory infiltration, increased collagen deposition, and derangement of mitochondrial cristae. 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 densitometry and troponin I (r 2 = 0.73; p < .05), and the correlation of PAR staining densitometry and left ventricular systolic stroke work index was r 2 = 0.33 (p = .0509). Conclusion: There is significant PARP activation in the hearts of septic patients with impaired cardiac function. We hypothesize that PARP activation may be partly responsible for the cardiac depression seen in humans with severe sepsis.

KW - Heart dysfunction

KW - Oxidative and nitrosative stress

KW - Peroxynitrite

KW - Poly(ADP-ribose) polymerase

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=33645805025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645805025&partnerID=8YFLogxK

U2 - 10.1097/01.CCM.0000206470.47721.8D

DO - 10.1097/01.CCM.0000206470.47721.8D

M3 - Article

VL - 34

SP - 1073

EP - 1079

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 4

ER -