Endotoxin disrupts beta-adrenergic signal transduction in the heart
D. D. Bensard, A. Banerjee, R. C. McIntyre Jr, R. L. Berens and A. H. Harken
Department of Surgery, University of Colorado Health Sciences Center, Denver.
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. CLINICAL
RELEVANCE: 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.
