Impaired beta-adrenergic receptor stimulation of cyclic adenosine monophosphate in human septic shock: association with myocardial hyporesponsiveness to catecholamines.
OBJECTIVE
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.


METHODS
Prospective study.


METHODS
Medical ICU in a university hospital.


METHODS
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).


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.
Department of Medicine, Pulmonary and Critical Care Division, University of Maryland School of Medicine, Baltimore.
H J
HJ
Silverman
R
R
Penaranda
J B
JB
Orens
N H
NH
Lee
D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000503:physiopathology*; D002395:Catecholamines / Q000494:pharmacology*; D016638:Critical Illness; D000242:Cyclic AMP / Q000032:analysis / Q000096:biosynthesis*; D004280:Dobutamine / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012772:Shock, Septic / Q000503:physiopathology*
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D000242:Cyclic AMP