The basis of the histamine assay in human skin: II. Wheal formation.

Abstract

1 Subepidermal injection of histamine solutions in isotonic saline in four subjects evoked whealing after a mean delay of 2.6 min, this estimate being derived by regression modelling. 2 Wheal growth was better modelled by the logarithm of time than by time, suggesting that wheal size depends upon assisted diffusion of histamine in the dermis. 3 Wheal growth was piecemeal, not continuous, consistent with the successive involvement of neighbouring vascular territories. 4 Wheal growth was completed by 9 min after injection.

Actions of terfenadine and cimetidine on histamine wheal formation.

“…In earlier work it was shown the histamine wheal growth begins after a delay of 1-2 min, and proceeds for up to 9-10 min from injection, growth occurring by piecemeal accretion of small territories, though at a general rate which accords with assisted diffusion in the skin from an initial area corresponding to that of the subepidermal injection bleb, i.e. about 41 mm2 [1,4]. In those analyses, data were fitted best by linear regression slopes.…”

“…Histamine tests were made between 11.00 h and 12.00 h in an air conditioned laboratory at 210 C + 1.5°C. The methods used have already been described in detail [1,4]; a solution of histamine acid phosphate in isotonic saline 1 mg ml-'1, was diluted to 1 in 4 and 1 in 16 to yield solutions equivalent to histamine free base, 0.3 mm and 0.074 mm. These were injected subepidermally, with a saline control in volumes of 0.1 ml of each, by tuberculin syringes with 25 gauge needles, into the palmar surface of the left forearm.…”

“…Regression analysis was done by BMDP 6D. Because time trends were not of prime interest in these experiments, having been analysed previously [1], the rates of growth or reduction in wheal size were measured by differencing the data, subtracting each from its predecessor, thus producing increments between the minute intervals of measurement and so removing trend [9]. Another reason for the differencing procedure is that wheal growth is a self-correlated process in time, each successive wheal area representing small accretions and removals of fluid from the preceding area.…”

“…Former work [1] had suggested that histamine wheal formation in human skin takes place by stepwise accretion of small territories to a central area about the injection site. Also, some work in animals and in man [2,3] had pointed to histamine H2-receptor involvement in the vascular response to histamine in skin.…”

“…Also, some work in animals and in man [2,3] had pointed to histamine H2-receptor involvement in the vascular response to histamine in skin. It was, therefore, decided to use the former methods [1] to study histamine wheal growth in those who had taken either an Hlor an H2-receptor antagonist or both, by exploring potential interaction between terfenadine and cimetidine as antagonists of injected histamine in skin.…”