Ear Blood Flow Research Articles

Myeloperoxidase-antineutrophil cytoplasmic antibody-associated sensorineural hearing loss

A 36-year-old female with hyperthyroidism that had been treated with propilthiouracil (PTU) complained of tinnitus and hearing loss in both ears. She was treated with steroid administration by an otolaryngologist; however, hearing continued to fluctuate when the steroids were tapered. Laboratory evaluation revealed a decreased complement level and elevated levels of immunoglobulin M (IgM) and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). With the withdrawal of PTU and high-dose methylprednisolone, she had excellent return of right-sided hearing. In recent years, there have been many reports about MPO-ANCA-associated small vessel vasculitis. Although any organ may be affected by this disease, there are no reports about MPO-ANCA-associated progressive hearing loss without any other organ involvement. The present case suggests the possibility that inner ear blood flow impairment due to ANCA-associated small vessel vasculitis induces the so-called autoimmune sensorineural hearing loss.

Comparison of the vascular innervation of the rat cochlea and vestibular system

In order to gain a better understanding of the neuronal and local control of inner ear blood flow, the vascular innervation to the rat cochlea and vestibular system was examined. Specimens were removed in toto beginning at the basilar artery extending to the anterior inferior cerebellar artery, labyrinthine artery, common cochlear artery, modiolar artery and anterior vestibular artery. When possible the vessels were dissected in continuity through the cribrose area. The vestibular endorgans were also removed. Specimens were examined using immunohistochemical techniques for the presence of vasoactive intestinal peptide, neuronal nitric oxide synthase, neuropeptide-Y, substance P and calcitonin gene related peptide. Results show that the vasculature to the cochlea and vestibular portion of the inner ear receive similar types of nonadrenergic innervation, that within the vestibular endorgans, only CGRP and SP were found in the neuroepithelium or in association with vessels, and that within the vestibular system, the majority of the vascular innervation appears to stop at or near the cribrose area. In the cochlea however, it extends to include the radiating arterioles. These findings suggest that cochlear blood flow is under finer control and that neuronally induced changes in blood flow may have a more global effect in the vestibular periphery.

Methysergide reduces nonnutritive blood flow in normal and scalded skin.

Methysergide is a serotonin antagonist and has been demonstrated to reduce wound blood flow and edema formation. We have determined the effect of methysergide on protein kinetics in normal and scalded skin of anesthetized rabbits. L-[ring-(13)C(6)]- or L-[ring-(2)H(5)]phenylalanine was used to reflect skin protein kinetics by use of an ear model, and L-[1-(13)C]leucine was used to reflect whole body protein kinetics. The results were that infusion of methysergide (2-3 mg. kg(-1). h(-1)) reduced the blood flow rate in normal skin by 50% without changing skin or whole body protein kinetics. After scald injury on the ear, administration of methysergide for 48 h reduced the weight of scalded ears (43 +/- 4 vs. 30 +/- 5 g, P < 0.01) and ear blood flow rate (42.6 +/- 4.9 vs. 5.8 +/- 1.0 ml. 100 g(-1). min(-1), P < 0.0001) and did not change wound protein kinetics. Methysergide reduced arteriovenous shunting and maintained inward phenylalanine transport from the blood to the skin pool. Using the microsphere technique, we found that the infusion of methysergide decreased blood perfusion by 33-36% in both normal and scalded ear skin. We conclude that methysergide administration reduces nonnutritive, as opposed to nutritive, blood flow in normal and scalded skin.

Synchronous changes in ear and tail blood flow following salient and noxious stimuli in rabbits

Simultaneous recordings were made of ear and tail blood flow during alerting responses to salient environmental stimuli in conscious rabbits, and during electrical stimulation of the spinal trigeminal tract and raphe pallidus in anesthetized rabbits. Blood flow fell in a highly correlated manner (Pearson coefficient ranging from 0.52 to 0.95) in these experimental situations. Salient stimuli in conscious rabbits, and noxious stimuli in anesthetized rabbits appear to cause a generalized vasoconstriction in cutaneous beds.

Autoregulation of Human Inner Ear Blood Flow During Middle Ear Surgery With Propofol or Isoflurane Anesthesia During Controlled Hypotension

Autoregulation of Human Inner Ear Blood Flow During Middle Ear Surgery With Propofol or Isoflurane Anesthesia During Controlled Hypotension

Raphe pallidus and parapyramidal neurons regulate ear pinna vascular conductance in the rabbit

We have determined whether alteration of neuronal function in raphe pallidus and the parapyramidal region alters ear blood flow, measured by an implanted Doppler ultrasonic probe, in anesthetized rabbits. Injection of GABA (5 nmol in 50 nl) increased ear flow from 6.0±0.1.0 to 31±10 kHz, without changing arterial pressure or heart rate. Focal electrical stimulation of raphe pallidus at low current amplitude caused ear pinna blood flow to fall from 41±6 to 9±3 kHz, again with little or no change in arterial pressure. These excitatory and inhibitory stimuli did not affect superior mesenteric blood flow. The fall in ear flow in response to electrical stimulation of raphe pallidus was not prevented by tetrodotoxin-mediated inhibition of the rostral ventrolateral medulla. Thus raphe pallidus and parapyramidal region may regulate ear pinna vascular conductance via a direct spinal projection.

Amygdala co-ordinates sudden falls in ear pinna blood flow in response to unconditioned salient stimuli in conscious rabbits

Tetrodotoxin (10 pmol in 300 nl of Ringer), injected bilaterally into the region of the amygdala in conscious rabbits, virtually abolished the sudden falls in ear pinna blood flow that normally occur in response to salient environmental stimuli (touching the animal's fur, slightly moving its cage, or applying or removing a drape covering the cage). Time spent at 0–20% of maximum flow values during a 10 min observation period, commencing 15 min after injection of tetrodotoxin, significantly decreased compared with the pre-injection control period (30±14 s compared with 286±24 s, P<0.01, n=8 rabbits) and the time spent at 70–100% of maximum flow values significantly increased (521±36 s compared with 127±29 s, P<0.01). Vehicle was injected on the day before tetrodotoxin injections in four of eight rabbits and on the day after tetrodotoxin injections in the other four rabbits, in a counterbalanced design. Rabbits fully recovered from the effects of tetrodotoxin in one day. Vehicle did not significantly affect the time spent at different flow percentage values. Falls in ear blood flow elicited by noxious stimuli (ear pinch, inhalation of formaldehyde vapor) occurred in a normal pattern after tetrodotoxin. Amygdaloid circuitry is thus necessary for the production of falls in ear pinna blood flow that occur in response to unconditioned non-noxious stimuli, but not for the falls that occur in response to unconditioned noxious stimuli in rabbits. In humans, the amygdaloid region may also be involved in co-ordinating falls in cutaneous blood flow occurring in response to salient or anxiety-evoking stimuli. Thus, discovery of the neural pathways by which amygdaloid circuitry alters ear pinna blood flow in rabbits may elucidate the manner in which similar cardiovascular changes occur in humans during anxiety reactions.

Autoregulation of Human Inner Ear Blood Flow During Middle Ear Surgery with Propofol or Isoflurane Anesthesia During Controlled Hypotension

Autoregulation of Human Inner Ear Blood Flow During Middle Ear Surgery with Propofol or Isoflurane Anesthesia During Controlled Hypotension

Improvement in inner ear blood flow by nitric oxide following experimentally induced cochlear thrombosis in anesthetized guinea pigs.

The nitric oxide (NO) donor sodium nitropruside (SNP) applied to the round window membrane has recently been found to increase cochlear blood flow (CoBF) in normal guinea pigs and in normal and presbyacusic mice. This study examined the effect of topical applications of SNP on experimentally impaired CoBF in anesthetized guinea pigs. Small (3 microliters) portions of 3% SNP were applied to the round window niche of both normal and thrombosed cochleas. Local vascular impairment was produced by ferromagnetic thrombosis of cochlear blood vessels and the microcirculation measured using laser Doppler flowmetry. Ferromagnetic thrombosis resulted in a mean decrease of CoBF to 52% of baseline. There was a clear improvement in mean CoBF to 84% of baseline by the topical application of SNP that depended on the degree of ischemic damage produced. Under neuroleptanalgesia and ketamine-xylazine anesthesia, significant increases in CoBF were measured in normal ears as well as in the thrombosed ones. However, several SNP applications were needed to improve the impaired CoBF, while a single portion was sufficient in the normal cochlea to cause a drastic increase in mean CoBF to 234% of baseline. In urethane-anesthetized animals, no flow increase was found despite repeated drug administration. Careful evaluation of the laser Doppler signals was necessary to accurately determine the concentrations of the moving blood cells and their mean velocities.

Inner Ear Blood Flow in the Rat after Unilateral Arterial Occlusion in the Vertebrobasilar Arterial System

Inner Ear Blood Flow in the Rat after Unilateral Arterial Occlusion in the Vertebrobasilar Arterial System

Inner Ear Blood Flow in the Rat after Unilateral Arterial Occlusion in the Vertebrobasilar Arterial System

It is generally accepted that certain kinds of vertigo and hearing disturbances are caused by blood flow insufficiency in the vertebrobasilar arterial system. Using the microsphere method we investigated whether unilateral vertebral artery or unilateral posterior inferior cerebellar artery occlusion could cause an imbalance between right and left inner ear blood flow in rats. We also studied the differential vulnerability between blood flow in the cochlea and in the ampullae of the three semicircular canals. We counted the numbers of microspheres distributed to the cochlea (CO) and microspheres distributed to three ampullae of semicircular canals (SC) under a microscope with the surface preparation method. The results were as follows: i ) no imbalances were observed between bilateral CO or SC even in animals with arterial occlusion, and ii ) the CO/SCs of animals with arterial occlusion were not significantly different from that of the control animals. These findings suggest that total inner ear blood flow over a certain period of time was even between the ears bilaterally even in animals with arterial occlusion. The blood flow in the ampullae of the three semicircular canals was not more or less affected by arterial occlusion than the blood flow in the cochlea.

ラット内耳のＣＯ２に対する血流増加反応の加齢変化

ラット内耳のＣＯ２に対する血流増加反応の加齢変化

内耳とホルモン

The possible roles of several hormones such as aldosterone, vasopressin, atrial natriuretic peptide (ANP) and catecholamines in the inner ear are reviewed on the basis of recent research results, including our data. The presence of a mineralocorticoid type I receptor, Na-K ATPase and amiloride-sensitive Na+ channels in the cells involved in the secretion and absorption of endolymph, such as the marginal cells, suggest that aldosterone may control endolymph secretion and absorption. The involvement of vasopressin in the homeostasis of the endolymphatic system, which has been suggested by several lines of evidence, remains to be clarified. Recent results have also suggested that ANP may control the secretion and absorption of endolymph in the inner ear, regulate cochlear nerve function, and control inner ear blood flow. Finally, recent evidence also suggests that catecholamines may regulate the function of the endolymphatic sac.

Arterial baroreflex modulation of heat-induced vasodilation in the rabbit ear.

The purpose of this study was to determine whether nonthermal baroreflexes arising from cardiopulmonary and/or arterial baroreceptors modulate rabbit ear blood flow (EBF) during hyperthermia. Intact and sinoaortic-denervated (SAD) rabbits were chronically instrumented with a Doppler ultrasonic flow probe for measurement of EBF velocity (kHz). During whole body heating in conscious rabbits, EBF and ear vascular conductance (EVC) increased as core temperature increased until maximal plateau levels of EBF and EVC were reached. The maximal plateau level of EVC attained during heat stress was lower in SAD than in intact rabbits. Subsequent intrapericardial administration of procaine at maximal EBF blocked cardiac afferents but did not alter EVC in either animal group. In a second experiment, ramp decreases in mean arterial pressure were produced by vena caval occlusion at maximal EBF. In intact rabbits, EBF and EVC decreased linearly as mean arterial pressure fell, but EBF and EVC did not decrease during vena caval occlusion in SAD rabbits. Thus neither pharmacological nor mechanical unloading of cardiac baroreceptors results in reflex vasoconstriction in the heat-stressed rabbit ear. However, baroreflexes arising from arterial baroreceptors may modulate EBF in heat-stressed rabbits.

Separation of peripheral and central cardiovascular actions of angiotensin II.

The pressor and vasoconstrictor action of angiotensin II (ANG II) is considered to be caused by a combination of its direct and indirect vascular effects, the latter mediated by the sympathetic nervous system. The purpose of this study was to determine the extent to which the direct and indirect actions of ANG II contribute to its pressor and vascular effects. Blood pressure, cutaneous vascular, and plasma norepinephrine responses to intravenous ANG II were measured in conscious rabbits before and after inhibition of central sympathetic outflow with intravenous and intracisternal clonidine and after ganglionic blockade with intravenous pentolinium. Intravenous ANG II caused a similar dose-related rise in blood pressure before and after sympathetic blockade with intravenous clonidine, intracisternal clonidine, and intravenous pentolinium. In contrast, the dose-related fall in cutaneous ear blood flow and cutaneous ear temperature and rise in cutaneous ear vascular resistance induced by intravenous ANG II were abolished after intravenous clonidine, intracisternal clonidine, and intravenous pentolinium. Heart rate was unchanged after ANG II. There were no changes in back skin or rectal temperature. There was a nonsignificant fall in plasma norepinephrine and no change in epinephrine after ANG II. These results demonstrate that the acute pressor response to intravenous ANG II is mediated by its direct vascular effects and is not dependent on central or ganglionic stimulation of the sympathetic nervous system, in contrast to the effect of ANG II on cutaneous ear vasoconstriction, which is predominantly caused by a centrally mediated increase in sympathetic nervous activity. Our results separate, in conscious rabbits, the direct vascular effects of ANG II from its indirect vascular actions, which are mediated by central sympathetic stimulation in the brain.

Acute increases in forebrain blood flow during alerting responses in conscious rabbits

We have previously shown that alerting responses (documented by appearance of theta rhythm in the hippocampal EEG) are associated with a characteristically timed acute vasoconstriction in the ear artery bed of the conscious rabbit. We have now determined what happens to forebrain blood flow (Doppler probe chronically implanted around the internal carotid artery) during similar alerting responses in conscious rabbits, comparing forebrain flow to simultaneously measured ear flow. During an alerting response, forebrain flow increased by 31±8% of baseline ( n=6, P<0.01), with the increase commencing within 1 s of the stimulus, at approximately the same time as the decrease in ear flow. Arterial pressure increased from 77±3 to 81±3 mmHg ( P<0.01), so that internal carotid conductance increased from 0.17±0.02 to 0.20±0.02 kHz/mmHg ( P<0.01). During a 1 h continuous recording period in the laboratory there was a negative correlation between forebrain and skin flow, with the Pearson coefficient in individual rabbits ranging from −0.18 to −0.62 ( n=6, all correlations P<0.01). During this period, forebrain blood flow was just as variable, from second to second, as distal aortic flow, but not as variable as ear blood flow. Our study thus demonstrates that alerting responses in rabbits are associated with rapid increases in cerebral vascular conductance. We believe that this is the first demonstration of this phenomenon in the conscious experimental animal.

The roles of cGMP and cAMP in active thermoregulatory vasodilation.

This study was designed to test the hypothesis that active thermoregulatory vasodilation (AVD) is the result of a neurotransmitter-induced adenosine 3',5'-cyclic monophosphate (cAMP) pathway interacting with a nitric oxide-induced guanosine 3',5'-cyclic monophosphate (cGMP) pathway. Rabbits were instrumented for measurement of arterial pressure and ear blood flow (EBF) and the infusion of drugs. In four groups of conscious animals, whole-body heating increased EBF from 0.5 +/- 0.3 to 8.3 +/- 1.3 kHz. In group 1 (n = 6), N(omega)-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor, 10-40 mg) reduced EBF from 7.1 +/- 0.9 to 1.9 +/- 0.5 kHz. Subsequent infusion of 8-bromo-cGMP (a cGMP analog, 5-10 mg) returned EBF to 6.2 +/- 0.7 kHz. In group 2 (n = 3), (R)-p-adenosine 3',5'-cyclic monophosphothioate (a cAMP-dependent protein kinase inhibitor, 10 mg) reduced EBF to 1.6 +/- 0.4 kHz. In group 3 (n = 6), nerve blockade of the ear (procaine, 20 mg/ml, 1.5 ml) reduced EBF from 8.6 +/- 1.3 to 1.6 +/- 0.3 kHz. Subsequent infusion of 8-bromo-cAMP (a cAMP analog, 5-10 mg) returned EBF to 8.3 +/- 2.0 kHz. In group 4 (n = 6), the infusion of L-NAME caused EBF to fall from 9.0 +/- 1.1 to 1.2 +/- 0.3 kHz. Infusion of the cAMP phosphodiesterase inhibitor Ro 20-1724 (0.2-0.5 mg) raised EBF to 5.5 +/- 0.7 kHz. These results suggest that cGMP plays a permissive role in AVD and indicate that the transmitter acts through cAMP.

Laser Doppler measurements of inner ear blood flow during experimental thrombosis of cochlear blood vessels in the guinea pig.

This study investigated the vascular effect of ferromagnetic obstruction of cochlear blood vessels in the guinea pig using dual-channel laser Doppler flowmetry. To improve this technique, we tested new types of magnets and iron spheres. In so doing, the cochlear temperature was lowered selectively and general hypothermia was avoided. The success of vascular impairment in the inner ear was found to depend on the experimental conditions used. Given normothermic conditions (38 degrees C body temperature), a clear reduction in cochlear blood flow (CBF) was found in only about 30% of the animals tested when an aluminium-nickel-cobalt alloy magnet and carbonyl iron spheres were used, while this ratio increased to about 80% under general hypothermia (33 degrees C). Using a stronger neodymium-iron-boron magnet and smaller-sized iron spheres, we found the success of vascular obstruction to be approximately 70% under normothermia and 100% with local hypothermia (to 33 degrees C) of the cochlea. Although the extent of vascular impairment revealed a considerable interindividual variation, the present findings demonstrate that ferromagnetic intervention in CBF with dual-channel laser Doppler flowmetry can be used to investigate the effect of quantified cochlear ischemia on inner ear physiology in the guinea pig model and test various therapeutic strategies.

The effect of CO2 and apnea on cochlear and middle ear blood flow in guinea pigs

The effect of 10% CO2 (in air) and apnea on cochlear blood flow (CBF) and middle ear blood flow (MEBF), capillary vessel diameters and blood pressure (BP) were investigated in guinea pigs. Intravital microscopic techniques (IVM) using video system, and laser Doppler flowmetry (LD) were used. MEBF was measured in the blood vessels of the middle ear mucosa over the cochlea and CBF was measured in the lateral wall vessels in the second or third cochlear turn. During 10% CO2 respiration for 10 min, the highest vessel diameter dilated about 11% in the middle ear and 5% in the cochlea. During 5 minutes apnea, the highest vessel diameter constricted about 30% in the middle ear and 5% in the cochlea. Elevation of PCO2 dilate blood vessels with constant PO2, but constriction of blood vessels as observed in extremely low PO2 range even if PCO2 was elevated. The ratio of the change in blood flow volume to the change in BP was obtained after the change in blood flow volume was calculated from blood flow velocity and blood vessel diameter. The mean change of ratio in MEBF was a 10% decrease with 10% CO2, 28% decrease with apnea in IVM. The mean change of ratio in CBF was a 44% increase with 10% CO2, 14% increase with apnea in IVM, 67% increase with 10% CO2, 42% increase with apnea, in LD. The change of CBF in LD was about 20% larger than in IVM. Our results showed that CBF belonging to vertebral artery system was more strongly maintained in association with autoregulation even under conditions of low PO2 or high PCO2 compared to MEBF in the external carotid artery system. It was suggested that blood flow behavior was significantly different between the middle ear and inner ear.

Cutaneous vasoconstriction in conscious rabbits during alerting responses detected by hippocampal theta-rhythm

We determined whether alerting stimuli cause cutaneous vasoconstriction in conscious rabbits. We compared ear blood flow with renal, mesenteric, and femoral flows at rest and in response to nonnoxious alerting stimuli, which induced theta-rhythm (4-9 Hz) in the simultaneously recorded hippocampal electroencephalogram (EEG). theta-Inducing stimuli (e.g., whistles and fur touches) reduced ear flow by 95 +/- 6%, commencing 1-2 s after the EEG change and lasting 45 s. Renal flow did not significantly change with alerting stimuli, mesenteric and femoral flows slightly decreased, arterial pressure transiently rose (+10 +/- 3 mmHg), and heart rate fell (+43 +/- 9 beats/min). At rest, the coefficient of variation for ear flow (62 +/- 6%) was greater than for other flows (P < 0.01). Phentolamine (1 mg/kg iv) reduced this coefficient to 29 +/- 4% (P < 0.01). Our study demonstrates that alerting responses in conscious rabbits are associated with selective cutaneous vasoconstriction, without increase in flow to skeletal muscle.