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Summary: We studied whether the human heart has spare receptors for [beta]-adrenoceptor-mediated positive inotropic effects. Thus, we assessed in right atria and left papillary muscles of patients with different degrees of heart failure under identical experimental conditions affinity {pK, values from (-)-[125I]iodocyanopindolol binding} and potency (pD2 values from contractile responses) for isoprenaline, adrenaline, and noradrenaline in comparison with rat heart. Plots of [beta]-adrenoceptor occupancy versus responses constructed from these data revealed that rat left atria and papillary muscles had a large receptor reserve for all three [beta]-adrenoceptor agonists: 50% of maximal response was produced with only 1-3% of [beta]-adrenoceptor occupancy. In human heart, however, receptor reserve was considerably lower: 50% of maximal response required 8-10% (in right atria) and 20-25% (in left papillary muscles) occupation of [beta]-adrenoceptors. Receptor reserve declined further with an increasing degree of heart failure (and decreasing [beta]-adrenoceptor number): in end-stage heart failure (New York Heart Association class IV) both in right atria and left papillary muscles a 1:1 ratio between [beta]-adrenoceptor occupancy and responses was observed. These data show that the human heart has only a small receptor reserve for [beta]-adrenoceptor agonists. This may explain why a decrease in [beta]-adrenoceptor number leads to a decrease in [beta]-adrenoceptor function early in the development of heart failure.

(C) Lippincott-Raven Publishers.