title: Comparison of non-invasive methods for the assessment of haemodynamic drug effects in healthy male and female volunteers: sex differences in cardiovascular responsiveness.
abstract: 1. The study was performed to determine the sensitivity and short-term and day-to-day variability of a novel technique based on laser interferometry of ocular fundus pulsations and of non-invasive methods for the quantification of haemodynamic drug effects. An additional aim was to assess sex differences in haemodynamic responsiveness to cardiovascular drugs in male and female healthy volunteers. 2. Ten males and nine females (age range 20-33 years) were studied in a double-blind, randomized, cross-over trial. Simultaneous measurements from systemic haemodynamics, laser interferometry of ocular fundus pulsations, systolic time intervals from mechanocardiography, a/b ratio from oxymetric fingerplethysmography and Doppler sonography of the radial artery were used to describe the haemodynamic effects of cumulative, stepwise increasing intravenous doses of phenylephrine, isoprenaline, sodium nitroprusside and of placebo. 3. Laser interferometry detected the isoprenaline-effects at the lowest dose level of 0.1 micrograms min-1 with a high signal-to-noise ratio. The reproducibility of measurements under baseline was high, no changes were observed after systemically effective doses of phenylephrine or sodium nitroprusside. Systolic time intervals were sensitive and specific for isoprenaline-induced effects, PEP and QS2c-measurements had high reproducibility. Fingerplethysmography proved a sensitive measurement for the detection of the vasodilating effects of sodium nitroprusside, but was not specific, and showed low reproducibility. Measurements from Doppler sonography had lower reproducibility and sensitivity compared with the other applied methods. 4. There was a significant sex difference for several of the haemodynamic parameters under baseline conditions; however, the responsiveness to the drugs under study was not different, when drug effects were expressed as %-change from the baseline. 5. Laser interferometry is a valuable non-invasive, highly sensitive and specific approach for the detection of pulse pressure changes. A battery of non-invasive tests appears useful for the characterization of cardiovascular drugs. Gender differences may not pose a relevant problem for the study of acute haemodynamic effects of cardiovascular drugs.
authors.affiliation: Department of Clinical Pharmacology, University of Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Wolzt
authors.forename: L
authors.initials: L
authors.lastname: Schmetterer
authors.forename: A
authors.initials: A
authors.lastname: Rheinberger
authors.forename: A
authors.initials: A
authors.lastname: Salomon
authors.forename: C
authors.initials: C
authors.lastname: Unfried
authors.forename: H
authors.initials: H
authors.lastname: Breiteneder
authors.forename: H
authors.initials: H
authors.lastname: Ehringer
authors.forename: H G
authors.initials: HG
authors.lastname: Eichler
authors.forename: A F
authors.initials: AF
authors.lastname: Fercher
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005654:Fundus Oculi; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007368:Interferometry; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D007834:Lasers; D008297:Male; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011674:Pulse / Q000187:drug effects; D017534:Radial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D015203:Reproducibility of Results; D012727:Sex Characteristics; D014463:Ultrasonography
chemical_list: D009599:Nitroprusside; D010656:Phenylephrine; D007545:Isoproterenol