3-Aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, improves hemodynamics and prolongs survival in a porcine model of hemorrhagic shock

Andrea Szabó, Paul Hake, Andrew L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Hypoxia, energy deficit, and oxidative damage are principal mechanisms of injury in hemorrhagic shock (HS). Oxidant-induced cellular energetic failure and cell dysfunction is mediated, in part, via the activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS). Here we examine the effect of the PARS inhibitor 3-aminobenzamide (3AB) in a severe HS model. Pigs were bled to a cardiac index of 40 mL/kg/min for 2 h, which was followed by saline resuscitation (20 mL/kg). Hypovolemia induced decreases in mean arterial blood pressure (to 40-42 mmHg), in both atrial pressures, in systemic oxygen consumption (by 26-30%), and in mixed venous saturation (by 65%). HS also caused lactic acidosis (4.0-5.5 mM). Fluid replacement with saline caused only a partial and transient recovery of blood pressure and cardiac output, with no recovery of stroke work during resuscitation. Fluid replacement did not prevent the progressive hemodynamic decompensation. The PARS inhibitor 3AB (15 mg/kg) significantly ameliorated the fall in blood pressure, cardiac output, and stroke work; slightly increased left atrial pressure during resuscitation; and significantly prolonged survival. PARS inhibition also prevented the reduction in oxygen consumption and mixed venous saturation during resuscitation. Taking these data together, we conclude that pharmacological inhibition of PARS exerts beneficial effects in a porcine model of severe HS. We propose that favorable action of 3AB is related, at least in part, to an improved cardiac performance.

Original languageEnglish (US)
Pages (from-to)347-353
Number of pages7
JournalShock
Volume10
Issue number5
StatePublished - Nov 1998
Externally publishedYes

Fingerprint

Poly Adenosine Diphosphate Ribose
Hemorrhagic Shock
Ligases
Swine
Resuscitation
Hemodynamics
Atrial Pressure
Oxygen Consumption
Cardiac Output
Arterial Pressure
Stroke
Blood Pressure
Lactic Acidosis
Hypovolemia
Enzyme Activation
Oxidants
3-aminobenzamide
Pharmacology
Wounds and Injuries

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

3-Aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, improves hemodynamics and prolongs survival in a porcine model of hemorrhagic shock. / Szabó, Andrea; Hake, Paul; Salzman, Andrew L.; Szabo, Csaba.

In: Shock, Vol. 10, No. 5, 11.1998, p. 347-353.

Research output: Contribution to journalArticle

@article{eab9a794671a4e41bc707b302fc68676,
title = "3-Aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, improves hemodynamics and prolongs survival in a porcine model of hemorrhagic shock",
abstract = "Hypoxia, energy deficit, and oxidative damage are principal mechanisms of injury in hemorrhagic shock (HS). Oxidant-induced cellular energetic failure and cell dysfunction is mediated, in part, via the activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS). Here we examine the effect of the PARS inhibitor 3-aminobenzamide (3AB) in a severe HS model. Pigs were bled to a cardiac index of 40 mL/kg/min for 2 h, which was followed by saline resuscitation (20 mL/kg). Hypovolemia induced decreases in mean arterial blood pressure (to 40-42 mmHg), in both atrial pressures, in systemic oxygen consumption (by 26-30{\%}), and in mixed venous saturation (by 65{\%}). HS also caused lactic acidosis (4.0-5.5 mM). Fluid replacement with saline caused only a partial and transient recovery of blood pressure and cardiac output, with no recovery of stroke work during resuscitation. Fluid replacement did not prevent the progressive hemodynamic decompensation. The PARS inhibitor 3AB (15 mg/kg) significantly ameliorated the fall in blood pressure, cardiac output, and stroke work; slightly increased left atrial pressure during resuscitation; and significantly prolonged survival. PARS inhibition also prevented the reduction in oxygen consumption and mixed venous saturation during resuscitation. Taking these data together, we conclude that pharmacological inhibition of PARS exerts beneficial effects in a porcine model of severe HS. We propose that favorable action of 3AB is related, at least in part, to an improved cardiac performance.",
author = "Andrea Szab{\'o} and Paul Hake and Salzman, {Andrew L.} and Csaba Szabo",
year = "1998",
month = "11",
language = "English (US)",
volume = "10",
pages = "347--353",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - 3-Aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, improves hemodynamics and prolongs survival in a porcine model of hemorrhagic shock

AU - Szabó, Andrea

AU - Hake, Paul

AU - Salzman, Andrew L.

AU - Szabo, Csaba

PY - 1998/11

Y1 - 1998/11

N2 - Hypoxia, energy deficit, and oxidative damage are principal mechanisms of injury in hemorrhagic shock (HS). Oxidant-induced cellular energetic failure and cell dysfunction is mediated, in part, via the activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS). Here we examine the effect of the PARS inhibitor 3-aminobenzamide (3AB) in a severe HS model. Pigs were bled to a cardiac index of 40 mL/kg/min for 2 h, which was followed by saline resuscitation (20 mL/kg). Hypovolemia induced decreases in mean arterial blood pressure (to 40-42 mmHg), in both atrial pressures, in systemic oxygen consumption (by 26-30%), and in mixed venous saturation (by 65%). HS also caused lactic acidosis (4.0-5.5 mM). Fluid replacement with saline caused only a partial and transient recovery of blood pressure and cardiac output, with no recovery of stroke work during resuscitation. Fluid replacement did not prevent the progressive hemodynamic decompensation. The PARS inhibitor 3AB (15 mg/kg) significantly ameliorated the fall in blood pressure, cardiac output, and stroke work; slightly increased left atrial pressure during resuscitation; and significantly prolonged survival. PARS inhibition also prevented the reduction in oxygen consumption and mixed venous saturation during resuscitation. Taking these data together, we conclude that pharmacological inhibition of PARS exerts beneficial effects in a porcine model of severe HS. We propose that favorable action of 3AB is related, at least in part, to an improved cardiac performance.

AB - Hypoxia, energy deficit, and oxidative damage are principal mechanisms of injury in hemorrhagic shock (HS). Oxidant-induced cellular energetic failure and cell dysfunction is mediated, in part, via the activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS). Here we examine the effect of the PARS inhibitor 3-aminobenzamide (3AB) in a severe HS model. Pigs were bled to a cardiac index of 40 mL/kg/min for 2 h, which was followed by saline resuscitation (20 mL/kg). Hypovolemia induced decreases in mean arterial blood pressure (to 40-42 mmHg), in both atrial pressures, in systemic oxygen consumption (by 26-30%), and in mixed venous saturation (by 65%). HS also caused lactic acidosis (4.0-5.5 mM). Fluid replacement with saline caused only a partial and transient recovery of blood pressure and cardiac output, with no recovery of stroke work during resuscitation. Fluid replacement did not prevent the progressive hemodynamic decompensation. The PARS inhibitor 3AB (15 mg/kg) significantly ameliorated the fall in blood pressure, cardiac output, and stroke work; slightly increased left atrial pressure during resuscitation; and significantly prolonged survival. PARS inhibition also prevented the reduction in oxygen consumption and mixed venous saturation during resuscitation. Taking these data together, we conclude that pharmacological inhibition of PARS exerts beneficial effects in a porcine model of severe HS. We propose that favorable action of 3AB is related, at least in part, to an improved cardiac performance.

UR - http://www.scopus.com/inward/record.url?scp=0032196891&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032196891&partnerID=8YFLogxK

M3 - Article

VL - 10

SP - 347

EP - 353

JO - Shock

JF - Shock

SN - 1073-2322

IS - 5

ER -