Beta-adrenergic stimulation enhances left ventricular diastolic performance in normal subjects.
To determine the effects of beta-adrenergic stimulation on transmitral Doppler echocardiography flow characteristics of left ventricular diastolic filling, we studied 10 healthy volunteers aged 23-31 years (mean age, 26.6 years) during intravenous infusion of isoprenaline in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 min). Saline control infusion was given in the same manner in a crossover and blinded protocol. Compared with the infusion of placebo, stepwise increasing doses of isoprenaline caused a dose-related increase in early and late diastolic filling velocities and velocity-time integrals, a lengthening of the acceleration time, and a shortening of the deceleration and filling time. The chosen method proved highly sensitive, as statistically significant changes were detectable at the lowest dose of 0.1 microgram/min for all variables except velocity-time integral of late filling and deceleration time (> or = 0.2 microgram/min). The effects related to dose in a log-linear fashion except for the lengthening of the acceleration time (early ceiling), the increase of peak early filling velocity (increased steepness at higher doses), and the shortening of the filling time. Inclusion of the associated increases in heart rate and systolic blood pressure and the decrease in diastolic blood pressure blunted all treatment contrasts except for the increase of peak early filling velocity. In addition, the hemodynamics with respect to heart rate and loading conditions were not altered at low dosages of drug (< 0.4 microgram/min). Effects of at least the peak early filling velocity must be interpreted as an active adrenergically mediated myocardial relaxation process. These findings have potentially important clinical implications for this noninvasive, readily available, and convenient technique in clinical pharmacology, stress testing, and possibly therapeutic interventions in diastolic dysfunction in humans.
Nixdorff
U
U
II. Medical Clinic, Johannes Gutenberg-University, Mainz, Germany.
de Mey
C
C
Belz
G G
GG
Erbel
R
R
Simon
H
H
Butzer
R
R
Schroeter
V
V
Meyer
J
J
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D016277:Ventricular Function, Left / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D007545:Isoproterenol