Effect of intravenous histamin on ocular blood flow

It is well known that histamine is a potent vasoactive substance. The vascular responses to histamine in any organ, show, however, a wide variability between species and vessels. The presence of histamine in the retina was shown in several species at concentrations comparable to those measured in the brain. This suggests that histamine, like in the brain, may play a role as an endogenous modulator of the retinal circulation. Histamine has been hypothesized to play a role in the development of diabetic retinopathy. However, there is a considerable lack of knowledge about the influence of histamine on retinal and choroidal blood flow in healthy humans. In a previous own study we have shown that intravenous histamine causes a 25% increase in mean flow velocity in the ophthalmic artery and a 10% increase in ocular fundus pulsation amplitude in healthy humans indicating histamine induced vasodilation in the eye. The aim of the present project is to further characterise the histamine system in the human eye. The study is divided into three parts (study A, B, C); all studies are performed in healthy volunteers. All measurement procedures are non-invasive and non-contactile. In Study A we investigate the effects of histamine on ocular blood flow in healthy humans. In this double-blind, two-way crossover study histamine is administered intravenously in three different dosages. The blood-flow measurements are done at each dose step. In studies B and C we examine the effects of two different histamine receptor antagonists (H1 blocker and H2 blocker, respectively) on retinal and choroidal hemodynamic parameters. Retinal and choroidal blood flow are assessed with laser Doppler velocimetry and laser Doppler flowmetry, respectively. The results of the present experiments will help to characterise the physiological and potential pathophysiological role of the histamine system in ocular blood flow regulation and ocular vascular disease.

The role of histamine in allergic reaction, inflammation and hypersensitive reactions is a matter of investigation for a long time. For the eye, it has also been shown that histamine, especially in allergic reactions, plays an important role in mediating these reactions. Whether or not histamine plays a role in the blood flow regulation of the posterior pole of the eye, has yet to be clarified. However, the high density of histamine receptors in retinal and choroidal vessels indicate a possible role of histamine in the regulation of ocular blood flow. In this project we have assessed the effect of intravenously administered histamine on ocular blood flow and investigated which of the known histamine receptors may be responsible for the histamine effects. For this purpose we have performed three different studies in young, healthy volunteers. Study A was designed to investigate the effect of intravenously administered histamine on ocular blood flow. In this experiment we could show that histamine increases choroidal but not retinal blood flow. In study B we have investigated whether cimetidine, a substance which blocks the histamine effect on the so-called H2 receptors, is able to blunt the histamine effect in the eye. However, the data gained from this experiment indicate that H2 receptor blocker does not abolish the histamine induced increase in choroidal blood flow. Thus, one can conclude that H2 receptors are not responsible for the histamine effect on choroidal blood flow. Study C aimed to test the hypothesis that H1 receptors are responsible for the histamine induced increase in blood choroidal blood flow. For this purpose, a H1 receptor blocker (diphenhydramine) was administered together with histamine. In this experiment the effect of histamine was almost totally blunted by co-administration of the H1 receptor blocker. In summary, one can conclude from these experiments that histamine induced effect on the posterior pole of the eye is mediated mainly by H1 receptors.