A comparative study in subjects with homozygous sickle cell disease and in normal subjects of responses evoked in forearm vasculature by mild, indirect cooling

Abstract

We have studied responses evoked in the forearm vasculature of twelve subjects with homozygous sickle cell disease (SS) and in eight dark-skinned controls of West Indian ancestry (AA) by mild cooling of the contralateral hand in water at 16°C for 2 min; this stimulus was repeated six times at randomized time intervals. Total forearm blood flow was measured by venous occlusion plethysmography, cutaneous red cell flux was monitored by a laser Doppler flowmeter and arterial pressure was recorded by semi-automatic sphygmomanometry. Of the AA subjects, three showed a decrease in total forearm vascular resistance (FVR, of -10%) in response to the first immersion and this reversed to an increase in FVR (+7%) by the sixth immersion. The remaining five showed an increase in FVR (+65%) which persisted until the sixth immersion (26%). By contrast, all SS subjects showed an increase in FVR (+32%) which persisted to the sixth stimulus (+27%). Further, on a scale of discomfort of 0–10, none of the AA subjects rated the cool stimulus higher than 0, whereas SS subjects gave a rating of 7 for the first stimulus which decreased to 5 by the sixth stimulus. Both AA and SS subjects showed an increase in arterial pressure and a tendency towards vasoconstriction in forearm skin. We propose that, as in Caucasian AA subjects, dark-skinned AA subjects showed a primary reflex vasoconstriction in forearm muscle in response to mild, indirect cooling which was overcome in some individuals by muscle vasodilatation of the alerting response that is evoked by novel or noxious stimuli. By contrast, in SS subjects, such muscle vasodilatation was not able to overcome the strong reflex vasoconstrictor response to cooling despite the perceived unpleasantness of the stimulus. The significance of these findings is discussed in relation to the initiation of painful crises in SS subjects.