H J Silverman1, R Penaranda, J B Orens, N H Lee. 1. Department of Medicine, Pulmonary and Critical Care Division, University of Maryland School of Medicine, Baltimore.
Abstract
OBJECTIVES: To determine whether myocardial hyporesponsiveness to administered catecholamines occurs in human sepsis and whether this phenomenon is associated with impaired beta-adrenergic receptor stimulation of cyclic adenosine monophosphate. DESIGN: Prospective study. SETTING: Medical ICU in a university hospital. PATIENTS: Normal human volunteers (n = 7), critically ill patients who were not septic (n = 9), septic patients not in shock (n = 16), and septic patients in shock (n = 17). MEASUREMENTS AND MAIN RESULTS: Pulmonary artery catheter-derived hemodynamic data were obtained in patients with sepsis and septic shock. Isoproterenol and sodium fluoride-stimulated cyclic adenosine monophosphate accumulations were measured in circulating lymphocytes. The hemodynamic response to sequential infusions of dobutamine, 5 and 10 micrograms/kg/min, was obtained in septic and septic shock patients. Baseline hemodynamic values for mean arterial pressure, cardiac index, left ventricular stroke work index, and oxygen delivery index at approximately 2 days after the onset of sepsis were significantly lower in septic shock patients compared with septic (nonshock) patients (p < .01 p < .05, p < .001, p < .01, respectively). Isoproterenol- and sodium fluoride-stimulated cyclic adenosine monophosphate accumulations were significantly reduced in septic shock patients compared with those accumulations observed in septic patients (p < .01 and p < .001, respectively). The heart rate response to 10 micrograms/kg/min of dobutamine was significantly (p < .01) lower in septic shock patients compared with septic patients. CONCLUSIONS: In patients with septic shock, impaired beta-adrenergic receptor stimulation of cyclic adenosine monophosphate is associated with myocardial hyporesponsiveness to catecholamines, suggesting that beta-adrenergic receptor dysfunction may contribute to the reduced myocardial performance observed in this shock state.
OBJECTIVES: To determine whether myocardial hyporesponsiveness to administered catecholamines occurs in humansepsis and whether this phenomenon is associated with impaired beta-adrenergic receptor stimulation of cyclic adenosine monophosphate. DESIGN: Prospective study. SETTING: Medical ICU in a university hospital. PATIENTS: Normal human volunteers (n = 7), critically illpatients who were not septic (n = 9), septic patients not in shock (n = 16), and septic patients in shock (n = 17). MEASUREMENTS AND MAIN RESULTS: Pulmonary artery catheter-derived hemodynamic data were obtained in patients with sepsis and septic shock. Isoproterenol and sodium fluoride-stimulated cyclic adenosine monophosphate accumulations were measured in circulating lymphocytes. The hemodynamic response to sequential infusions of dobutamine, 5 and 10 micrograms/kg/min, was obtained in septic and septic shockpatients. Baseline hemodynamic values for mean arterial pressure, cardiac index, left ventricular stroke work index, and oxygen delivery index at approximately 2 days after the onset of sepsis were significantly lower in septic shockpatients compared with septic (nonshock) patients (p < .01 p < .05, p < .001, p < .01, respectively). Isoproterenol- and sodium fluoride-stimulated cyclic adenosine monophosphate accumulations were significantly reduced in septic shockpatients compared with those accumulations observed in septic patients (p < .01 and p < .001, respectively). The heart rate response to 10 micrograms/kg/min of dobutamine was significantly (p < .01) lower in septic shockpatients compared with septic patients. CONCLUSIONS: In patients with septic shock, impaired beta-adrenergic receptor stimulation of cyclic adenosine monophosphate is associated with myocardial hyporesponsiveness to catecholamines, suggesting that beta-adrenergic receptor dysfunction may contribute to the reduced myocardial performance observed in this shock state.
Authors: Hendrik Bracht; Enrico Calzia; Michael Georgieff; Joel Singer; Peter Radermacher; James A Russell Journal: Br J Pharmacol Date: 2012-04 Impact factor: 8.739
Authors: Andrea Morelli; Stefano De Castro; Jean-Louis Teboul; Mervyn Singer; Monica Rocco; Giorgio Conti; Leonardo De Luca; Emanuele Di Angelantonio; Alessandra Orecchioni; Natesa G Pandian; Paolo Pietropaoli Journal: Intensive Care Med Date: 2005-04-06 Impact factor: 17.440