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 dia stolic filling, we studied 10 healthy volunteers aged 23-31 years (mea n age, 26.6 years) during intravenous infusion of isoprenaline in cons ecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 mu g/min (each for 15 mi n). Saline control infusion was given in the same manner in a crossove r and blinded protocol. Compared with the infusion of placebo, stepwis e increasing doses of isoprenaline caused a dose-related increase in e arly and late diastolic filling velocities and velocity-time integrals , a lengthening of the acceleration time, and a shortening of the dece leration and filling time. The chosen method proved highly sensitive, as statistically significant changes were detectable at the lowest dos e of 0.1 mu g/min for all variables except velocity-time integral of l ate filling and deceleration time (greater than or equal to 0.2 mu g/m in). The effects related to dose in a log-linear fashion except for th e lengthening of the acceleration time (early ceiling), the increase o f peak early filling velocity (increased steepness at higher doses), a nd the shortening of the filling time. Inclusion of the associated inc reases in heart rate and systolic blood pressure and the decrease in d iastolic blood pressure blunted all treatment contrasts except for the increase of peak early filling velocity. In addition, the hemodynamic s with respect to heart rate and loading conditions were not altered a t low dosages of drug (<0.4 mu g/min). Effects of at least the peak ea rly filling velocity must be interpreted as an active adrenergically m ediated myocardial relaxation process. These findings have potentially important clinical implications for this noninvasive, readily availab le, and convenient technique in clinical pharmacology, stress testing, and possibly therapeutic interventions in diastolic dysfunction in hu mans.