Endotoxin disrupts beta-adrenergic signal transduction in the heart.
BACKGROUND
Nonsurvivors of septic shock demonstrate impaired myocardial function refractory to the administration of beta-agonists.


METHODS
Using the isolated rat heart preparation, the integrity of the beta-adrenergic transduction pathway was tested (rate pressure product, rate of contraction, rate of relaxation, and cyclic adenosine monophosphate content) using isoproterenol hydrochloride (beta-receptor agonist) or colforsin (forskolin) (adenylyl cyclase activator) stimulation following intracoronary endotoxin infusion.


RESULTS
Basal rate pressure product, rate of contraction, rate of relaxation, and cyclic adenosine monophosphate concentrations were unaffected by endotoxin infusion. Endotoxin impaired, increases in rate pressure product, rates of contraction and relaxation, and cyclic adenosine monophosphate to isoproterenol (P < .05), but the response to colforsin was unaffected by endotoxin.


CONCLUSIONS
Endotoxin disrupts the myocardial response to direct beta-receptor stimulation but not to adenylyl cyclase stimulation in the isolated rat heart.


CONCLUSIONS
Alteration of the proximal beta-adrenoreceptor complex by endotoxin suggests that therapy of the failing heart during refractory septic shock may be directed to intact sites distal in the beta-adrenergic pathway.
Bensard
D D
DD
Department of Surgery, University of Colorado Health Sciences Center, Denver.
Banerjee
A
A
McIntyre
R C
RC
Berens
R L
RL
Harken
A H
AH
D000262:Adenylyl Cyclases / Q000187:drug effects; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004731:Endotoxins / Q000009:adverse effects*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012486:Salmonella typhimurium; D015398:Signal Transduction / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
D004731:Endotoxins; D008070:Lipopolysaccharides; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol