An investigation of components of variance and tachyphylaxis in a placebo‐controlled intravenous tyramine study

Abstract

AimsTo explore inter-and intra-volunteer variability for the dose of intravenous tyramine eliciting a 20 mmHg increase in systolic blood pressure from baseline (T YR20) and to evaluate potential tachyphylaxis. MethodsTwelve healthy volunteers received blinded placebo-controlled ascending and descending sequences of intravenous tyramine injections on two separate occasions. The TYR20 was derived by linear interpolation, using three interventions to deal with missing data. ResultsAnalysis of covariance ( ANCOVA ) demonstrated no significant difference in TYR20 between sequences, regardless of the missing data methodolog y applied. Inter-volunteer variability was 2.4-3.4 times larger than within-volunteer variability. No evidence of tachyphylaxis was seen using either the sign test or generalized additive models. ConclusionsSince inter-volunteer variability was greater than intra-volunteer variability, a crossover study design would be a more efficient study design, and the descending sequence of injections could be omitted since tachyphylaxis was not demonstrated.

Oral vitamin C enhances the adrenergic vasoconstrictor response to local cooling in human skin

“…Oral Asc tended to increase baseline SkBF at both sites from ϳ30 min after the ingestion, although the potential effect of Asc on baseline SkBF was overlapped on the recovery from tyramine-induced changes in SkBF at site 1. To avoid the confounding effects of remaining vasoconstrictor action and tachyphylaxis due to tyramine administration at the same sites (6), SkBF data at site 2 was used for analyzing the effect of oral Asc on vasoconstrictor response. Changes in forearm CVC as relative values in response to LC in experiment 3 are shown in Fig.…”