TY - JOUR
T1 - Effects of adrenomedullin on load and myocardial performance in normal and heart-failure dogs
AU - Lainchbury, John G.
AU - Meyer, Donna M.
AU - Jougasaki, Michihisa
AU - Burnett, John C.
AU - Redfield, Margaret M.
PY - 2000
Y1 - 2000
N2 - Myocardial actions of the vasodilator peptide adrenomedullin (ADM) in the intact animal are unknown. Negative and positive inotropic actions have been reported in ex vivo experiments. Myocardial and load-altering actions of ADM in dogs before and after development of heart failure were studied. With controlled heart rate (atrial pacing) and after β-blockade, ADM was administered to five normal dogs in doses of 20 ng·kg-1·min-1 iv, 100 ng·kg-1·min-1 iv, and 200 ng·kg-1·min-1 into the left ventricle (LV). LV peak systolic pressure and end-systolic volume decreased with each dose of ADM. End-systolic pressure decreased with the two higher doses. At the highest dose, arterial elastance and the time constant of LV isovolumic relaxation (τ) decreased, and LV end-systolic elastance (E(es)) increased. LV end-diastolic pressure and volume were unchanged. In five additional normal dogs receiving only the highest dose of ADM (200 ng·kg-1·min-1 intra-LV), to control for increased heart rate and sympathetic activation observed with the cumulative infusion, ADM produced arterial vasodilation but no change in E(es) or τ. In four dogs with pacing-induced heart failure, ADM (200 ng·kg-1·min-1 intra-LV) was without effect on τ, E(es), and systolic or diastolic pressure and volume. In vivo, ADM appears to be a selective arterial dilator without inotropic or lusitropic effects. The vasodilatory actions are attenuated in heart failure.
AB - Myocardial actions of the vasodilator peptide adrenomedullin (ADM) in the intact animal are unknown. Negative and positive inotropic actions have been reported in ex vivo experiments. Myocardial and load-altering actions of ADM in dogs before and after development of heart failure were studied. With controlled heart rate (atrial pacing) and after β-blockade, ADM was administered to five normal dogs in doses of 20 ng·kg-1·min-1 iv, 100 ng·kg-1·min-1 iv, and 200 ng·kg-1·min-1 into the left ventricle (LV). LV peak systolic pressure and end-systolic volume decreased with each dose of ADM. End-systolic pressure decreased with the two higher doses. At the highest dose, arterial elastance and the time constant of LV isovolumic relaxation (τ) decreased, and LV end-systolic elastance (E(es)) increased. LV end-diastolic pressure and volume were unchanged. In five additional normal dogs receiving only the highest dose of ADM (200 ng·kg-1·min-1 intra-LV), to control for increased heart rate and sympathetic activation observed with the cumulative infusion, ADM produced arterial vasodilation but no change in E(es) or τ. In four dogs with pacing-induced heart failure, ADM (200 ng·kg-1·min-1 intra-LV) was without effect on τ, E(es), and systolic or diastolic pressure and volume. In vivo, ADM appears to be a selective arterial dilator without inotropic or lusitropic effects. The vasodilatory actions are attenuated in heart failure.
KW - Hemodynamics
KW - Inotrope
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U2 - 10.1152/ajpheart.2000.279.3.h1000
DO - 10.1152/ajpheart.2000.279.3.h1000
M3 - Article
C2 - 10993761
AN - SCOPUS:0033830668
SN - 0363-6135
VL - 279
SP - H1000-H1006
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 3 48-3
ER -