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Biomedical subjects

K A Ohlsén

Publications and source records attributed to K A Ohlsén.

3 recordsLinked to original sources

Cochlear blood flow in response to dilating agents.

Reduced cochlear blood flow (CBF) has been implicated in various pathologies of the inner ear, including sudden deafness, noise-induced hearing loss and Meniere's disease. Thus the aim of some current therapeutic regimens to treat these conditions is to increase CBF and thereby improve oxygenation of the inner ear tissues. Most of the vasodilating agents in clinical use, however, do not have specific experimental evidence to support their effects on CBF. The hypotension which can follow systemic administration may limit their local effectiveness and general utility, just as it complicates the interpretation of the data in animal experiments. In the current study we investigated the effect of six agents, known for their systemic cardiovascular actions, on CBF: hydralazine, sodium nitroprusside, papaverine, nicotinic acid, verapamil and histamine. The effect of these drugs was studied after topical applications on the round window membrane (RWM) and systemic intravenous administrations. CBF was monitored with a laser Doppler flowmeter (LDF). Topical administration of sodium nitroprusside was the most effective in increasing CBF, followed, in order, by hydralazine and histamine. No change in CBF was observed for papaverine, verapamil or nicotinic acid. Systemic administrations of all the agents caused a marked decrease in blood pressure and variable effects on CBF. We discuss the CBF changes in relation to the different pharmacological mechanisms of action of each drug. The study demonstrates the effectiveness of topical application of vasodilating agents in increasing CBF.

Administration, Topical↗

Cochlear blood flow and microvascular resistance changes in response to hypertonic glycerol, urea, and mannitol infusions.

The effect of hyperosmotic agents on cochlear blood flow (CBF) was tested in normal guinea pigs and in guinea pigs having prior unilateral operations to ablate the endolymphatic duct. Laser-Doppler-measured CBF was normalized to remove apparent changes related directly to systemic blood pressure. Hyperosmotic fluids were given via venous infusion: glycerol (20% and 40% solutions), urea (10%, 30%, and 40% solutions), and mannitol (40% solution). All agents were dissolved in 0.9% saline and the mixtures were given at a rate of 0.3 to 0.6 mL/min for 5 minutes. Control infusions were of 0.9% saline and isotonic dextran 70 (Pharmacia). All hyperosmotic infusions resulted in similar increases in normalized cochlear blood flow (nCBF) that extended to a maximum of 300% of the baseline value in a dose-dependent way during the infusion time period. Within approximately 30 minutes following infusions, nCBF had returned to baseline levels. Saline infusion alone had little effect on nCBF, but isotonic dextran 70 gave a sustained increase to 122% of the baseline levels. There was no difference between the responses of nCBF in hydropic and normal cochleas for either control or hyperosmotic solutions. Measurements of systemic hematocrit at time intervals during and following the infusions showed that transient reductions of up to approximately 8% (for the maximum osmotic challenge) occurred during the infusion. It is concluded that the hyperosmotic treatments tested here are equally effective for short-term enhancements of nCBF in both normal and hydropic cochleas. The basis of the flow increase is partially rheologic and partially due to a local vasodilation.

Animals↗

Influence of topically applied adrenergic agents on cochlear blood flow.

This study was designed to assess the role of adrenergic receptors in the control of cochlear blood flow. Laser Doppler flowmetry was used to determine the effects of adrenergic drugs topically applied to the round window membrane of the cochlea. The relative influence of the various receptor types (alpha 1, alpha 2, beta 1, and beta 2) was examined by a selection of agonists and antagonists. The agonists norepinephrine and epinephrine, which have mixed alpha- and beta-receptor effects, and phenylephrine, a strong alpha 1-agonist, all induced a dose-dependent reduction in cochlear blood flow. The agonists isoproterenol (beta-active), salbutamol (alpha 2-active) had no effect on cochlear blood flow. Of the antagonists, when tested alone, only the selective alpha 1-antagonist prazosin had a direct effect on cochlear blood flow, demonstrating an increase in cochlear blood flow. The selective alpha 2-antagonist idazoxan, the beta-antagonist propranolol, and the unselective alpha-antagonist phentolamine had no effect on cochlear blood flow. Interaction studies of agonists and antagonists were performed to specifically define the receptor subclasses responsible for the cochlear blood flow increases with norepinephrine and epinephrine. The results are consistent with the presence of an alpha 1-adrenergic sympathetic control of cochlear blood flow.

Administration, Topical↗