Intravenous Administration of Diphenhydramine Reduces Histamine Induced Vasodilator Effects in the Retina and the Choroid

Abstract

Purpose: : Intravenous administration of histamine causes an increase in choroidal blood flow and retinal vessel diameters in healthy subjects. The receptor mediating this response has not yet been identified. In the present study we set out to clarify whether H₁ receptor blockade with diphenhydramine affects the hemodynamic response of histamine in the choroid and the retina.

Methods: : A randomized, double masked, placebo–controlled two–way cross–over study was performed in 18 healthy, male non smoking subjects. Histamine (0.32µg/kg/min over 30 minutes) was infused intravenously in the absence (NaCl as placebo) or presence of the H₁ blocker diphenhydramine (1.0mg/min over 50 min). Ocular hemodynamic parameters, blood pressure and intraocular pressure were measured before drug administration, after infusion of diphenhydramine or placebo and after co–infusion of histamine. Subfoveal choroidal blood flow and fundus pulsation amplitude were measured with laser Doppler flowmetry and laser interferometry, respectively. Retinal arterial and venous diameters were measured with a Retinal Vessel Analyzer. Retinal blood velocity was assessed with bi–directional laser Doppler velocimetry.

Results: : Administration of histamine caused a decrease in mean arterial pressure by –4±9% (ANOVA p=0.01). This effect was blunted by co–administration of diphenhydramine (ANOVA, p=0.04). Histamine significantly increased fundus pulsation amplitude (FPA) and subfoveal choroidal blood flow (ChBF). Co–administration of diphenhydramine significantly reduced this effect (ANOVA, FPA p=0.001, ChBF p=0.049). Histamine significantly increased retinal arterial diameter by +3.5±4.5% and retinal venous diameter by +3.7±2.8%. Again co–administration of diphenhydramine significantly reduced the vasodilating effect to +0.3±5.5% for retinal arteries (ANOVA, p=0.00006 ) and to +0.9±2.5% for retinal veins (ANOVA, p=0.004).

Conclusions: : The present data confirm that histamine increases choroidal blood flow and retinal vessel diameters in healthy subjects. Administration of the H₁ receptor blocker diphenhydramine significantly reduced this histamine induced changes in ocular perfusion parameters. These results strongly indicate that in the retina and choroid, H₁ receptors are involved in the histamine mediated hemodynamic effects in vivo.

Keywords: blood supply • choroid • retina