Angiogenesis: possible analogies between the eye and the inner ear.

Angiogenesis is a phenomenon concerning both physiological conditions linked to development and pathological conditions; in the latter it is aimed at providing an enhancement in blood supply to tumours, on one hand, and to restore the circulation in peripheral arterial and ischemic diseases, on the other hand, thus resulting in a controversial effect depending on the circumstances. When occurring in the eye, angiogenesis clearly proved to represent a threaten, whereas an univocal interpretation of the action of angiogenesis on the inner ear homeostasis is still lacking despite the morphologic and functional analogies between eye and labyrinth. These analogies can raise same doubt on the supposed role of angiogenesis in terms of preserving the function of a threatened inner ear: even this organ could be further damaged by microvascular disorders and/or mechanical changes able to jeopardize its architecture and consequently its function. If a parallelism between ear and eye is extendable to this aspect, this could open new perspectives in the treatment of certain affections of the inner ear by borrowing therapeutic strategies that have given appreciable and consolidate responses in the treatment of degenerative retinopathy.

Diuretics in Meniere disease: a therapy or a potential cause of harm?

Despite the lack of clear evidence for their effectiveness in treating vertigo, tinnitus, hearing loss and aural fullness, diuretics, represent a common treatment for Meniere disease (MD), as they are supposed to decrease volume and pressure in the endolymphatic partition of the labyrinth. Our group have outlined the possibility of an adverse effect on inner ear function derived from an abrupt lowering of blood pressure: a subsequent exaggerated vasomotor response inducing local ischemia could be responsible for more or less permanent damage. The inner ear, owing both to its terminal vascular supply and to the necessity of a steady metabolism, seems a reliable target for any hemodynamic imbalance that acutely affect its perfusion. In our opinion, the complexity of the inner ear anatomy and function argues against the usefulness of diuretics to reduce endolymphatic volume, in analogy to their effect on the volemia: too many active mechanisms and "buffer" systems are involved in the labyrinth. Even considering that the finding of mean low pressure values is relatively common in subjects with MD, an attempt should be to maintain a stable blood perfusion to the labyrinth; in fact, an abrupt decrease in systemic blood pressure can trigger an adverse sympathetic reaction and transmit misleading information to the cochlear vasopressin receptors.

Meniere's disease and the use of proton pump inhibitors.

PRINCIPLES: On the basis of previous observations we examined the possibility of a favourable effect of proton pump inhibitors (PPI) on Meniere's disease (MD). A preliminary step was made by retrospectively analysing the number of menieric crisis in group of patients suffering from MD and using PPI for other reasons as compared to a group of menieric subjects who had never used PPI. METHODS: Between January 2001 and December 2006, 42 patients affected by MD were examined in the tertiary referral centre at the University Hospital of Bologna, Italy and in the private office of an ENT specialist in Cassino, Italy. Within the study group, 18 patients had used PPI for various reasons for at least 12 consecutive months, whilst 24 patients had never been prescribed them. We recorded the number of menieric crises reported in the observation period. The mean follow-up period was 21.9 months. Statistical analysis was performed by means of the x2 test and significance was defined when p<0.05. RESULTS: Most of MD patients (72%) using PPI suffered less than one episode of menieric crisis/year. On the other hand patients who had never used a PPI, experienced considerably more episodes only 16.7% having less than one crisis per year. This difference was statistically significant (p<0, 001). CONCLUSIONS: Even taking the limitations of this retrospective study into account the reported data nevertheless strongly suggest a possible role for proton pumps in the pathogenesis of MD. This could lead to interesting developments and contribute to a better definition of MD and the therapeutic possibilities.

Exploring the reasons why melatonin can improve tinnitus.

Melatonin has been proposed as a treatment for tinnitus, especially on the basis of its favourable effects on sleep and its vasoactive and antioxidant properties. However, to our knowledge no attempts of interpretation have been advanced through a detailed analysis of the various specific properties of melatonin possibly cooperating in a coincidental way to relieve tinnitus: among these, its modulatory effect on central nervous system resulting in a protective mechanism against an exaggerated sympathetic drive; its capacity to induce a more steady hemodynamic condition, through a multifactorial and multi-organ activity, resulting in a more regular labyrinthine perfusion; a possible action on the skeletal muscle tending to a reduction of the muscular tone, which could relieve tinnitus of muscular origin deriving from tensor tympani tonic contractions; its possible reported antidepressive effect, which could indirectly act on tinnitus; a direct regulation of inner ear immunity as proposed in literature when melatonin was reported to be present in the inner ear. All these observations seem to indicate melatonin as a tool deserving a greater attention than other antioxidants in the attempt of relieving tinnitus, justifying its application from a more precise rationale based on a series of physio-pathological aspects.

Tinnitus as a warning for preventing vasovagal syncope.

It has been widely outlined by our group the possibility that a sufferance of the inner ear can take place as a consequence of hemodynamic imbalance which could affect young and healthy people and recognize a merely functional origin. As reported in previous papers, an altered reaction of the autonomic nervous system could actually jeopardize the labyrinthine perfusion even in absence of other damages. From this standpoint, the hypothesis that a hyperactivity of the vagal response to an acute sympathetic drive may result in an inner ear sufferance deserves to be explored. A mechanism which appears to fit to this model is represented by the Bezold-Jarisch reflex (BJR), which is considered to be responsible for vasovagal syncope and is characterized by a dynamic reasonably compatible with our findings. According to these premises, especially considering that the inner ear has a less active protective mechanism against ischemia as compared to brain, in predisposed subjects tinnitus, when considered as an initial symptom of inner ear hypoperfusion, can represent a warning able to prevent the lack of consciousness related to the syncope.

Possible influence on heart rate on tinnitus.

Assuming the possibility of the inner ear damage due to a hemodynamic imbalance essentially due to an abnormal vasomotor regulatory response, the possibility that heart rate (HR) has a correlation with the onset and/or the enhancement of tinnitus is hypothesized. In fact, recent studies have drawn the influence of other factors than blood pressure, in normotensive subjects, in taking part to the regulation of peripheral resistance, outlining the importance of both cardiac output (CO) - which is a function of heart rate (HR) and stroke volume (SV) and SV itself as a dynamic component to baroreflex control of muscle sympathetic nerve activity (MSNA). From this point of view, it could be possible that a condition of bradycardia can enhance tinnitus regardless of its cause, and conversely that a more elevated HR can be related to a relief of this symptom.

The possible role of proton pump inhibitors of the homeostasis of the inner ear.

The possibility of a benefit in some cases of inner ear sufferance by using proton pump inhibitors has been considered after a casual observation. The hypothesis is advanced considering the adverse effect of reflux on the eustachian tube function, the possible influence of the latter on inner ear symptoms and, from a more general point of view, the trigger effect which a gastric dysfunction requiring proton pump inhibitors could exert on the sympathetic system. These considerations, deserving a further study, seem to be based on logical assessment and therefore in our opinion deserve to be kept in mind in trying to define inner ear disorders of uncertain origin.